SPRINGER BRIEFS IN PLANT SCIENCE

Münir Öztürk · Volkan Altay

Khalid Rehman Hakeem
Eren Akçiçek

Liquorice
From Botany to
Phytochemistry

123
SpringerBriefs in Plant Science
SpringerBriefs present concise summaries of cutting-edge research and practical
applications across a wide spectrum of fields. Featuring compact volumes of 50
to 125 pages, the series covers a range of content from professional to academic.
Typical topics might include:
• A timely report of state-of-the art analytical techniques
• A bridge between new research results, as published in journal articles, and a
contextual literature review
• A snapshot of a hot or emerging topic
• An in-depth case study or clinical example
• A presentation of core concepts that students must understand in order to make
independent contributions
SpringerBriefs in Plant Sciences showcase emerging theory, original research,
review material and practical application in plant genetics and genomics, agronomy,
forestry, plant breeding and biotechnology, botany, and related fields, from a global
author community. Briefs are characterized by fast, global electronic dissemination,
standard publishing contracts, standardized manuscript preparation and formatting
guidelines, and expedited production schedules.

More information about this series at http://www.springer.com/series/10080

Münir Öztürk Volkan Altay
•

Khalid Rehman Hakeem

Eren Akçiçek

Liquorice
From Botany to Phytochemistry

123
Münir Öztürk Khalid Rehman Hakeem
Department of Botany and Center for Department of Biological Sciences
Environmental Studies King Abdulaziz University
Ege University Jeddah, Saudi Arabia
Izmir, Turkey

Eren Akçiçek
Volkan Altay Department of Gastroenterology, Faculty of
Department of Biology, Faculty of Science Medicine
and Arts Ege University
Mustafa Kemal University Izmir, Turkey
Hatay, Turkey

ISSN 2192-1229 ISSN 2192-1210 (electronic)

SpringerBriefs in Plant Science
ISBN 978-3-319-74239-7 ISBN 978-3-319-74240-3 (eBook)
https://doi.org/10.1007/978-3-319-74240-3
Library of Congress Control Number: 2018930380

© The Author(s) 2017

This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part
of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations,
recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission
or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar
methodology now known or hereafter developed.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this
publication does not imply, even in the absence of a specific statement, that such names are exempt from
the relevant protective laws and regulations and therefore free for general use.
The publisher, the authors and the editors are safe to assume that the advice and information in this
book are believed to be true and accurate at the date of publication. Neither the publisher nor the
authors or the editors give a warranty, express or implied, with respect to the material contained herein or
for any errors or omissions that may have been made. The publisher remains neutral with regard to
jurisdictional claims in published maps and institutional affiliations.

Printed on acid-free paper

This Springer imprint is published by the registered company Springer International Publishing AG
part of Springer Nature
The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland
 Glycyrrhiza flavescens ssp. flavescens
Glycyrrhiza glabra (at the top)
(right side)

Glycyrrhiza glabra root (in the centre) Glycyrrhiza echinata (lower side)
Dedicated to

Abu Ali Husayn ibn Abd Allah ibn Sina

(Avicenna)
(980–1037 CE)

An important figure as a physician, astronomer,

thinker and writer, accepted as the father of
early modern medicine due to the book he wrote
“el-Kanun fi’t-Tıb”or “Canon of Medicine”-
incorporates the work of Galen, as well as
ancient Ayurvedic, Arabian and Persian texts as
well as his own theories of medicine. His influ-
ence on the development of medicine across
much of the world has been quite significant.
(Image from google search—who is Avisena
SML 710  1024, from Ms. Tel Asiado—a writer,
author, content producer—from google search)
Preface

According to the famous medicine man “Avicenna,” there are men on our mother
earth who have wit but no religion, and the men who have religion but no wit,
ecologically speaking all things have causes, knowledge of anything is not com-
plete unless you know its causes as such in medicine we must know the causes of
sickness and health. This book deals with the health benefits of liquorice
(Glycyrrhiza), a widely used plant as herbal medicine and one of the most exten-
sively investigated medicinal plants of the world. The roots and stolons have been
used as food, and in traditional the root is well known to the herb dealers as well as
traditional medicine men for over 4000 years. It has been used against the treatment
of many ailments including the diseases of lung, heart, and kidney; arthritis,
eczema, gastric ulcer, low blood pressure, allergies, liver toxicity, and certain
microbial infections. The extract of this plant contains sugars, starch, resins,
essential oils, tannins, inorganic salts, and low levels of nitrogenous constituents
such as proteins, individual amino acids, and nucleic acids. A large number of
biologically active compounds have been isolated from Glycyrrhiza species, where
triterpene saponins and flavonoids are the main constitutes.
In this introductory book, we have tried to present a global perspective of
liquorice with a detailed historical background and attempt has been made to bridge
the gap between botany, ecology, treatment of diseases, molecular and pharma-
ceutical aspects. Along with the discussions on the recent studies on the phyto-
chemical and pharmacological aspects, some side and toxicity effects have also
been evaluated. The information on bioactive components has been presented at
length. The book also presents details on the taxonomy of this genus at global level,

ix
x Preface

as well as its industrial use and economical importance. Some information on its
ecology, cultivation, genetics, and biotechnology has also been included. We hope
it will prove of great help to the workers involved in the research aspects of
liquorice.

Izmir, Turkey Münir Öztürk

Hatay, Turkey Volkan Altay
Jeddah, Saudi Arabia Khalid Rehman Hakeem
Izmir, Turkey Eren Akçiçek
Contents

1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
2 Botany . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
2.1 Taxonomy and Morphology . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
2.2 Pollen Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
2.3 Distribution in the World . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
3 Ecology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
4 Ecophysicological Aspects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
5 Liquorice–Mycorrhiza Interactions . . . . . . . . . . . . . . . . . . . . . . . . . 31
5.1 Glycyrrhiza glabra . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
5.2 Glycyrrhiza uralensis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
5.2.1 Arbuscular Mycorrhizal Colonization . . . . . . . . . . . . . . 34
5.2.2 Effects on the Liquorice Development
with or Without AM Fungal Inoculation . . . . . . . ..... 35
5.2.3 Effects on Root Oxidase Activity and Phosphorus
and Potassium Uptake . . . . . . . . . . . . . . . . . . . . ..... 35
5.2.4 Glycyrrhizin Production . . . . . . . . . . . . . . . . . . . ..... 36
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..... 38
6 Molecular Aspects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
6.1 Cytogenetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
6.2 Genetic and Biotechnology . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43

xi
xii Contents

7 Pharmacological Activities and Phytochemical Constituents . . . . . . 45

7.1 Phytochemistry of Components . . . . . . . . . . . . . . . . . . . . . . . . . 46
7.1.1 Flavanoids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
7.1.2 Saponins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
7.1.3 Phenolic Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . 49
7.1.4 Coumarins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
7.1.5 Essential Oils and Other Compounds . . . . . . . . . . . . . . . 51
7.2 Bioactive Components and Biological Functions . . . . . . . . . . . . 53
7.2.1 Glycyrrhizic Acid and 18b-Glycyrrhetinic Acid . . . . . . . 54
7.2.2 Liquiritin, Isoliquiritin, Liquiritigenin, and
Isoliquiritigenin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
7.2.3 Dehydroglyasperin C and D . . . . . . . . . . . . . . . . . . . . . 59
7.2.4 Glabridin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
7.2.5 Carbenoxolone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
8 Economic Importance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .... 73
8.1 Traditional Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .... 73
8.2 Industrial Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .... 74
8.2.1 Liquorice as an Industrial Resource: A Case Study
from Japan . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
8.3 Other Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82
8.3.1 Liquorice Drinks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82
8.3.2 Meyan Balı (the Succus Liquiritiae) . . . . . . . . . . . . . . . 82
8.3.3 Use as Animal Feed . . . . . . . . . . . . . . . . . . . . . . . . . . . 84
8.3.4 Use as Dye Plant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84
8.3.5 Evaluation of Liquorice Wastes . . . . . . . . . . . . . . . . . . . 85
8.3.6 Antimicrobial and Antifungal Activity . . . . . . . . . . . . . . 86
8.3.7 Antiviral Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90
8.3.8 Anti-inflammatory . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
8.3.9 Anti-ulcer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
8.3.10 Anti Tumor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
8.3.11 Antioxidant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
8.3.12 Hepatoprotective Activity . . . . . . . . . . . . . . . . . . . . . . . 96
8.3.13 Dermatological Effect . . . . . . . . . . . . . . . . . . . . . . . . . . 97
8.3.14 Antidepressant and Memory-Enhancing Activity . . . . . . 97
8.3.15 Immunoregulatory Activity . . . . . . . . . . . . . . . . . . . . . . 98
8.3.16 Inhibitory Effect on Diabetes . . . . . . . . . . . . . . . . . . . . 99
8.3.17 Adrenal Cortical Hormone-like Function . . . . . . . . . . . . 100
8.3.18 Other Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100
8.3.19 Side Effects and Toxicity . . . . . . . . . . . . . . . . . . . . . . . 102
8.3.20 Other Alternative Uses . . . . . . . . . . . . . . . . . . . . . . . . . 107
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108
Contents xiii

9 Cultivation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
10 Global Perspectives and Future Approaches . . . . . . . . . . . . . . . . . . 133
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
11 Concluding Remarks and Future Directions of Research . . . . . . . . 135
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
Chapter 1
Introduction

The genus Glycyrrhiza (Liquorice) includes well-known traditional medicinal plants

growing in several regions of the world. The stolon and roots of the plants have been
used in traditional medicine by humans for over 4000 years and it has been described
as “the grandfather of herbs” (Ody 2000). Glycyrrhiza genus consists of about 30
taxa, of which only 15 taxa have been studied so far (Blumenthal et al. 2000; Sultana
et al. 2010; Chopra et al. 2013; Altay et al. 2016). The plants included in the genus
Glycyrrhiza are perennial herbs native to the regions in the Mediterranean, central and
southern Russia, Asia Minor, and parts of Iran. It is now widely cultivated throughout
Europe, the Middle East, and Asia (Blumenthal et al. 2000).
The plant has a long history of medicinal uses in Eurasia. It is believed to be
effective in treating peptic ulcer disease, constipation, cough, diabetes, cystitis,
tuberculosis, wounds, kidney stones, lung ailments, Addison’s disease, colds, and
painful swellings (Varshney et al. 1983; Dafni et al. 1984; Arseculeratne et al.
1985; Fujita et al. 1995; Yarrnell 1997; Gray and Flatt 1997; Rajurkar and Pardeshi
1997; Armanini et al. 2002; Chopra et al. 2002; Sharma and Agrawal 2013). It has
also been used for its anabolic properties and its capacity to improve male sexual
function (Sircar 1984; Nisteswar and Murthy 1989).
The name “Glycyrrhiza” comes from Greek words (glukos: sweet, rhiza: root)
meaning “sweet root”. Liquorice has a long and honorable history in the service of
humanity as it has been used medicinally long before the time of Christ. In the
fourth century B.C., the Greek botanist and contemporary of Aristotle,
Theophrastus (ca. 370–288/5 B.C.), refers to liquorice as “Scythian root” or “sweet
root” in his Enquiry into Plants (Theophrastus 1916). This ancient herbalist was
also interested in the history of liquorice and claims that the Scythians, whose
civilization was established early in the first millennium B.C., used liquorice and
mare’s milk cheese and could subsequently abstain from drinking for 11 or 12 days.
He also mentions that liquorice is useful in treating asthma when administered with
honey. Roots of this plant have been used in other areas of the ancient world, the
Brahmans of India, the Hindus, Greeks, Romans, Babylonians, and Chinese
(Chopra and Chopra 1958; Chopra et al. 1958). Nature’s medicine has recorded that
the earliest evidence of the use of liquorice goes back to the first syllables of
recorded time. It has been mentioned throughout the history and has been included
in the records of Pharaohs and Prophets. Generous supplies have been discovered in
the Emperor Tut’s grave as well as in other tombs of ancient Egyptian pharaohs;
Egyptian hieroglyphics record the use of Liquorice as a popular beverage by

© The Author(s) 2017 1

M. Öztürk et al., Liquorice, SpringerBriefs in Plant Science,
https://doi.org/10.1007/978-3-319-74240-3_1
2 1 Introduction

humans in the days when the Bible was still being written (Lucas 1976). During the
Middle Ages, early medical practitiponers like Ibn Sinna (Avicenna, 980–1037)
have written about liquorice in his “Canone” (EMA 2013). He mentions that
liquorice is used to treat many illnesses but mainly drunk as a tonic as a remedy for
cold and cough. Glycyrrhiza is one of the main treatments in the traditional med-
icine (Davis and Morris 1991). Alexander the Great, the Scythian armies, Roman
Emperor Caesar, and even Hindu prophet, Brahma, are on record endorsing the
beneficial aspects of liquorice (Oğuz 1987). Warriors used it for its ability to quench
thirst while on the March, while others (including Brahma and venerable Chinese
Buddhist sages) recognized Liquorice’s valuable healing properties (Rogers 2014).
In Chinese medicine, it has been used for over 4.000 years as a tonic to rejuvenate
the heart and spleen, and as a treatment for ulcers, cold symptoms, and skin dis-
orders. Chinese prepared it most often as medicinal tea (Fernie 1897). Recently, a
sample of historic liquorice from 756 A.D. was analyzed and found to still have
active principles (Sigurjonsdottir et al. 1995, 2001).
Pedanius Dioscorides of Anazarba present-day Tarsus in Turkey has given the
name “glukurrhiza” for the sweet flavoring root or stem of Glycyrrhiza glabra, the
first part of the word glukus means “sweet”, and the rhiza means “root”. Chinese too
have named it as “gao cao-sweet root”. Generally, three plants are identified under
liquorice G. glabra, Glycyrrhiza uralensis, and Glycyrrhiza inflata (Kao et al. 2014).
The commonly known “liquorice” is accepted as G. glabra. This “sweet wood”
belongs to Fabaceae (Leguminosae) family (Chopra and Chopra 1958). Forever, it
has got many vernacular names such as Sa em (Latin America); Réglisse, boisdoux
(France); Lakritze, Süssholz (Germany); Spanish liquorice, Orozuz, Ragaliz (Spain);
Lakrids, Lakridsplante (Denmark); Zoethout (Netherlands); Lagritsa-magusjuur
(Estonia); Lakritskasvi, Lakritsi (Finland); Glikrriza, (Greece); Édesfa, Igazi
édesgyökér (Hungary); Lakkrís (Iceland); Liquirizia (Italy); Lakrisrot (Norway);
Lukrecja gladka (Poland); Lakrits (Sweden); Lakrichnik, Russian liquorice (Russia);
Kan tsau, Gancao (China); Kanzou (Japan); Yashtimadhu, Atimadhuram, Madhuka
(India); Arpsous, Arq-sous, Aslussiesa, Asla-soos (Arabic); Shirin bajan, Ausareha
mahaka (Persian); Noekiyu (Myanmar); and Susu (Kiswahili) in different regions in
the world (Rao 1993; Blumenthal et al. 2000; Chopra et al. 2002; Nomura et al. 2002;
Anagha et al. 2012; Damle 2014; Rogers 2014). It is also known as meyan, bıyan,
boyam, miyan, payan, piyam, tatlı bayram, tatlı biyan, tatlı kök, biyam balı, sus, and
süs in different regions of Turkey and other Turkic Republics (Akan and Balos 2008).

References

Akan H, Balos M (2008) GAP Bölgesi’nden toplanan meyan kökü (Glycrrhiza glabra L.)
taksonunun ihracat durumu, etnobotanik özellikleri ve tıbbi önemi. Fırat Üniversitesi Fen ve
Mühendislik Bilimleri Dergisi 20(2):233–241 (In Turkish)
Altay V, Karahan F, Öztürk M, Hakeem KR, Ilhan E, Erayman M (2016) Molecular and
ecological investigations on the wild populations of Glycyrrhiza L. taxa distributed in the East
Mediterranean Area of Turkey. J Plant Res 129(6):1021–1032
References 3

Anagha K, Manasi D, Priya L, Meera M (2012) Comprehensive review on historical aspect of

Yashtimadhu-Glycyrrhiza glabra L. Global J Res Med Plants Indigen Med 1(12):687–693
Armanini D, Fiore C, Mattarello MJ, Bielenberg J, Plermo M (2002) History of the endocrine
effects of licorice. Exp Clin Endocrinol Diabetes 110:257–261
Arseculeratne SN, Gunatilaka AAL, Pnabokke RG (1985) Studies on medicial plants of Srilanka.
Part 14. Toxicity of medicinal herbs. J Ethnopharmacol 13:323–335
Blumenthal M, Goldberg A, Brinckmann J (2000) Herbal medicine: expanded commission E
monographs. Integrative Medicine Communications, Newton, MA
Chopra RN, Chopra IC (1958) Indigenous drugs of India, 2nd edn. Academic Publishers, Kolkata,
pp 183–187
Chopra RN, Chopra IC, Handa KL, Kapoor LD (1958) Chopra’s indigenous drugs of Indian, II
edn. UN Dhur & Sons Pvt. Ltd., Calcutta, India
Chopra RN, Nayar SL, Chopra IC (2002) Glossary of Indian medicinal plants. Niscair, Csir, New
Delhi
Chopra PKPG, Saraf BD, Inam F et al (2013) Antimicrobial and antioxidant activities of methanol
extract roots of Glycyrrhiza glabra and HPLC analysis. Int J Pharm Pharmacol Sci 5(2):
157–160
Dafni A, Yaniv Z, Palevitch D (1984) Ethnobotanical survey of medicinal plants in northern Israel.
J Ethnopharmacol 10:295–310
Damle M (2014) Glycyrrhiza glabra (Liquorice)-a potent medicinal herb. Int J Herb Med 2
(2):132–136
Davis EA, Morris DJ (1991) Medicinal uses of licorice through the millennia: the good and plenty
of it. Mol Cell Endocrinol 78(1):1–6
EMA (European Medicines Agency) (2013) Assessment report on Glycyrrhiza glabra L. and/or
Glycyrrhiza inflata Bat. and/or Glycyrrhiza uralensis Fisch., radix. Committee on Herbal
Medicinal Products, pp 3–40
Fernie WT (1897) Herbal simples. Boericke and Tafel, Philadelphia, PA
Fujita T, Sezik E, Tabata M, Yeşilada E, Honda G, Takeda Y (1995) Traditional medicine in
Turkey VII. Folk medicine in middle and regions. Econ Bot 49:406–422
Gray AM, Flatt PR (1997) Nature’s own pharmacy: the diabetes perspective. Proc Nutr Soc
56:507–517
Kao T-C, Wu C-H, Yen G-C (2014) Bioactivity and potential health benefits of licorice. J Agric
Food Chem 62:542–553
Lucas (1976) Nature’s medicines. Melvin Powers/Wilshire Book Company. No. Hollywood, CA,
pp 89–94
Nisteswar K, Murthy VK (1989) Aphrodisiac effect of indigenous drugs-A myth or reality. Probe
28:89–92
Nomura T, Fukai T, Akiyama T (2002) Chemistry of phenolic compounds of licorice (Glycyrrhiza
species) and their estrogenic and cytotoxic activities. Pure Appl Chem 74:1199–1206
Ody P (2000) The complete guide medicinal herbal. Dorling Kindersley, London, p 75
Oğuz G (1987) Meyan kökü ve önemi, vol 2(37). Fırat Üniversitesi Basın Bülteni, p 3
Rajurkar NS, Pardeshi BM (1997) Analysis of some herbal plants from India used in the control of
mellitus by NAA and AAS techniques. Appl Radiat Isot 48:1059–1062
Rao KVS (1993) A review on Licorice. Ancient Sci Life XIII(1–2):57–88
Rogers M (ed) (2014) Licorice. In: Herbalpedia. http://www.herbalpedia.com
Sharma V, Agrawal RC (2013) Glycyrrhiza glabra-A plant for the future. Mintage J Pharm Med
Sci 2(3):15–20
Sigurjonsdottir HA, Ragnarsson J, Franzson L, Sigurdsson G (1995) Is blood pressure commonly
raised by moderate consumption of liquorice? J Hum Hypertens 9:345–348
Sigurjonsdottir HA, Franzson L, Manhem K, Ragnarsson J, Sigurdsson G (2001) Liquorice-induced
rise in blood pressure: a linear dose-response relationship. J Hum Hypertens 15:549–552
Sircar NN (1984) Pharmaco-therapeutics of dasemani drugs. Ancient Sci Life 3:132–135
4 1 Introduction

Sultana S, Haque A, Hamid K et al (2010) Antimicrobial, cytotoxic and antioxidant activity of

methanolic extract of Glycyrrhiza glabra. Agr Bio J N Am 1(5):957–960
Theophrastus (1916) Enquiry into plants and minor works on odours and weather signs (trans: Sir
Arthur Hort), Book IX. Chap. 8. Par. 2. William Heineann, London/G.P. Putnam’s Sons, New
York
Varshney IP, Jain DC, Srivastava HC (1983) Study of saponins from Glycyrrhiza glabra root. Int J
Crude Drug Res 21:169–172
Yarrnell E (1997) Botanical medicine for cystitis. Altern Complement Ther 3(4):269–275
Chapter 2
Botany

2.1 Taxonomy and Morphology

The first attempt to create a botanical nomenclature came from the German botanist
Leonhard Fuchs (1501–1566) who accurately describes and characterizes this plant.
Works of The Works of eminent Arabic scientists Al Razi contributed much in this
direction during the same period. In the eighteenth century, the Neapolitan chemist
and philosopher Giuseppe Donzelli described liquorice, referring to it by its modern
name. The Swedish naturalist Carl von Linne (1707–1778) proceeded to subdivide
plants into genus and species and identified three different species of Glycyrrhiza:
G. glabra, G. echinata, and G. hirsuta (Fiore et al. 2005). However, latest scientific
classification of genus Glycyrrhiza reported by Bremer et al. (2009) according to
“Angiosperm Phylogeny Group classification (APG III) system” is as follows:
Kingdom: Plantae; unranked: Angiospermae; unranked: Eudicots; unranked:
Rosids; Order: Fabales; Family: Fabaceae; Subfamily: Faboideae; Tribe:
Galegeae;
The genus Glycyrrhiza (Fabaceae-Leguminosae) includes approximately 30 taxa
belonging to 21 species (Fig. 2.1). These are as follows:
1. Glycyrrhiza acanthocarpa (Lindl.) J. M. Black,
2. G. aspera Pall.,
3. G. astragalina Hook. & Arn.,
4. G. bucharica Regel,
5. G. echinata L.,
6. G. eglandulosa X. Y. Li,
7. G. eurycarpa P. C. Li,
8. G. foetida Desf.,
9. G. foetidissima Tausch,
10. G. frearitis (Boiss.) Orph. ex Beck,
11. G. glabra L.,
12. G. gontscharovii Maslenn,
13. G. iconica Hub.-Mor.,
14. G. inflata Batalin,
15. G. korshinskyi Grig.,
16. G. lepidota Pursh,

© The Author(s) 2017 5

M. Öztürk et al., Liquorice, SpringerBriefs in Plant Science,
https://doi.org/10.1007/978-3-319-74240-3_2
6 2 Botany

1 2 3

4 5 6

7 8 9

10 11 12

Fig. 2.1 Some Glycyrrhiza species natural distributed worldwide (www.theplantlist.org).

1 Glycyrrhiza aspera Pall; 2 G. eglandulosa X. Y. Li; 3 G. foetidissima Tausch; 4 G. acantho-
carpa (Lindl.) J. M. Black; 5 G. yunnanensis P. C. Li; 6 G. echinata L.; 7 G. korshinskyi Grig;
8 G. pallidiflora Maxim.; 9 G. uralensis Fisch.; 10 G. foetida Desf.; 11 G. astragalina Hook. &
Arn.; 12 G. lepidota Pursh

17. G. pallidiflora Maxim.,

18. G. squamulosa Franch.,
19. G. triphylla Fisch. & C. A. Mey.,
20. G. uralensis Fisch, and
21. G. yunnanensis P. C. Li (www.theplantlist.org).
G. glabra, which is known in commerce as liquorice, is most important
Glycyrrhiza species naturally distributed in Turkey. In Turkey, it is represented by
eight taxa (Davis 1970; Sümbül et al. 2003; Altay et al. 2016):
2.1 Taxonomy and Morphology 7

1. G. aspera Pall.,
2. G. asymmetrica Hub.-Mor.,
3. G. echinata L.,
4. G. flavescens Boiss ssp. flavescens,
5. G. flavescens ssp. antalyensis Sümbül et al.,
6. G. glabra L. var. glabra;
7. G. glabra L. var. glandulifera (Waldst. & Kit.) Regel & Herder, and
8. G. iconica Hub.-Mor.
Liquorice is a perennial herb or undershrub, erect growing up to about 2 m tall,
simple or branched from the base, stems striate with raised ridges especially above,
glabrous or sparingly pilose, and furnished throughout with sessile, shining, viscid
glands. Stipules brownish membranous, ca. 2 mm, subulate, falling early. Leaves
imparipinnate, 10–25 cm long, petiole 1-5-3 cm, petiole and rhachis ± ridged,
often pilose at least below, densely glandular; leaflets in 4–8 pairs, lanceolate,
elliptic, ovate or oblong, 20–40 (−55)  5–18 (−25) mm, entire, acute or retuse
above, densely punctate-glandular on the lower surface, hairy on the midrib below
and with scattered hairs occasionally also on the surface, glabrous and eglandular
above; petiolules ca. 2 mm, commonly pilose. Inflorescence racemose, elongate
and lax or shorter and more compact, shorter than or sub-equalling, rarely much
longer than the subtending leaf, flowers very shortly pedicellate; peduncles
1-5-3 cm., glandular and shortly hairy; bracts ca 1 mm. lanceolate, brownish
membranous falling early. Caly  4–6 mm, tubular, glabrous or sparingly hairy,
glandular, teeth lanceolate, the upper pair broader and slightly shorter, fused below,
the lower 3 narrower and about equalling the tube. Corolla pinkish blue to purple;
standard elliptic-lanceolate, 9–12  3–5 mm, acute or acuminate at the apex,
attenuate to a short claw below; wings 7–10 mm, lamina falcate-oblong, acute, 3
times as long as the claw, auricles short and blunt; keel 6–8 mm, lamina narrowly
oblong, shortly acuminate, about twice as long as the claw. Pod linear-oblong,
compressed, ca. 5 mm. wide, up to 30 mm long according to the number of seeds
(1–7), straight or almost so, shortly beaked, glabrous or glandular, ± constricted
between the seeds, tardily dehiscent. Seeds subspherical, smooth, ca 2.5–3 mm,
light to dark brown. Flowering-fruiting is from June to August (Davis 1970; Sofia
and Walter 2009).
Karaca (1992) has studied the liquorice from two different areas, with the aim of
determining whether there are morphological and anatomical differences in different
parts especially rhizomes, stem, and leaves of G. glabra. She has investigated the
specimens naturally distributed in the States of Izmir and Muş in Turkey. Her
results can be summarized as follows:
• The cross sections of leaves have revealed that the lower and upper epidermis in
Muş specimens are covered with a wider cuticle layer as compared to Izmir
specimens, and intercellular spaces in the spongy parenchyma are wider.
• Stem cross sections show that cortex layer is wider in the Izmir than Muş
specimens, phloem schlerenchymatic bundles form larger island in Muş speci-
mens, and rhomoidal crystals are found in the phloem cells in these specimens.
8 2 Botany

• The cross sections of the rhizome reveal that the periderm layer is found in the
samples belonging to both regions but periderm cell line is less stratified in Izmir
samples when compared to the Muş samples; the schleranchyma cell bundles in
Izmir specimens show regular order in the appearance of the lesser rays.
General morphological features of some taxa belonging to the genus Glycyrrhiza
are outlined below in detail (Komarov 1933–1964; Davis 1970; Nomura et al.
2002; Sofia and Walter 2009; www.plantnet.rbgsyd.nsw.gov.au; www.eol.org.):
Glycyrrhiza glabra L. Sparsely pubescent. erect perennial, 30–60 cm. Leaflets
5–9-paired, 15–45  10–20 mm, elliptic. Inflorescence 5–9 cm, lax, elongate.
Calyx teeth c. 3 mm. Corolla 9–11 mm, blue to violet. Legume 15–25  4–5 mm.
-terete, red-brown, glandular (sometimes bristly) or eglandular. 1–6-seeded. Fl. 6–7.
Cultivated ground, alluvial river valleys, sand dunes, etc., s.l.-1800 m.
G. glabra also includes three varieties worldwide (Davis 1970; Nomura et al.
2002; Sofia and Walter 2009):
1. G. glabra var. glabra (Turkish and Persian liquorice): This plant shows violet
flowers, legume, and ovary eglandular.
2. G. glabra var. glandulifera (Russian liquorice): It has a big root stock along
with a number of elongated roots but does not bear stolons. Legume and ovary
with at least a few stalked or sessile glands.
3. G. glabra var. typica (Spanish and Italian liquorice): This plant has purplish
blue-colored papilionaceous flowers. It gives out large number of stolons.

Glycyrrhiza echinata L. Erect, glabrescent, bushy perennial, l(−2) m. Leaflets

4–8-paired, 15–30  7–15 mm, lanceolate to broadly elliptic. Inflorescence
2–5 cm, dense, globose to elongate. Calyx teeth c. 1 mm. Corolla 5–7 mm, white
to mauve. Legume 12–16  6–8 mm, compressed, echinate, red-brown,
1–3-seeded. Fl. 6–7. Marshy ground. edges of ditches, etc., s.l.-1250 m.
Glycyrrhiza aspera Pall. Prostrate, sparsely pubescent perennial; stems 10–20 cm.
Leaflets 2–4-paired, 10–30  7–18 mm, elliptic. Inflorescence 2–5(−6) cm, dense
to lax, shortly cylindrical. Calyx 7–9 mm, teeth 2.5–4 mm. Corolla 14–17 mm,
reddish mauve with white inner petals. Legume 15–30 xc. 3 mm, curved, terete,
smooth, constricted between the seeds, 2–8-seeded. Fl. 5. Edges of cornfields,
730 m.
Glycyrrhiza iconica Hub.-Mor. Sparsely pubescent perennial, 20–30 cm. Leaflets
2–4-paired, 15–23  10–17 mm, teeth 2.5–4 mm. Corolla 18–20 mm, lilac. Ovary
glabrous, 4-seeded. Fruit unknown. Fl. 5–6.
Glycyrrhiza flavescens Boiss. Perennial herb, 30–85 cm. Leaflets 5–8-paired,
25–40  10–15 mm, elliptic. Inflorescence 8–20 cm, many-flowered. Calyx teeth
c. 3 mm. Corolla 12–18 mm, golden-yellow. Legume c, 4  1 cm, compressed,
glabrous, dark brown, valves contorting on dehiscence, several-seeded. Fl. 4.
Cornfields, macchie and Arbutus-Styrax woodland, nr. s.l.-500 m.
2.1 Taxonomy and Morphology 9

Glycyrrhiza asymmetrica Hub.-Mor. A much branched, bristly perennial,

30–70 cm. Leaflets 2–4-paired, 30–40  20–30 mm, widely obovate to
orbicular-cuneate. Inflorescence c. 3 cm. dense. Calyx teeth 3–5 mm. Corolla
15–16 mm, yellow. Fruit 4  1.5 cm oblong, acuminate, compressed, echinate,
brown, 2-seeded. Fl. 5–7. Macchie and Pinus brutia woodland, 30–350 m.
Glycyrrhiza acanthocarpa (Lindl.) J. M. Black Erect subshrub to 1 m high, ±
glabrous. Leaves 2–8 cm long; leaflets 9–13, linear to elliptic or obovate,
15–20 mm long; 2–8 mm wide, apex shortly mucronate, margins with minute,
curved hairs, gland-dotted; stipules 3–5 mm long. Racemes spike-like, exceeding
the leaves; peduncles 3–6 cm long; bracts filiform, 3–4 mm long. Calyx 3–4 mm
long, teeth ± equal to tube. Corolla purple 5–8 mm long; standard lanceolate;
wings shorter, linear-oblong; keel shortest, acute. Pod ovoid, 5–6 mm long, bristly,
rusty-colored; seeds c. 2.5 mm long, green mottled black. It flowers from early
spring through to late summer and produces single-seeded pods covered in hard
bristles or prickles. Seeds of G. acanthocarpa are kidney-shaped and attractively
colored, usually olive green, mottled with black46. Seeds are quite small, being
about 2.5 mm long and about 5 mg (Bell et al. 2010). G. acanthocarpa occurs from
the semi-arid to arid fringe of southern Australia’s cropping regions, thus appears
well adapted to water-limited environments with a winter dominant growing sea-
son. It occurs in various habitats and soil types from sandy to clay soils but is
especially common on soils prone to flooding (Bell et al. 2010).
Glycyrrhiza yunnanensis P. C. Li Herbs, perennial. Stem 60–100 cm tall, densely
scaly glandular punctate, sparsely pubescent. Leaves 8–10 cm; stipules lanceolate,
5–7 mm long, 2–3 mm wide, glandular punctate, glabrous; petiole densely scaly
glandular punctate, densely villous; leaflets 7–15, lanceolate or ovate-lanceolate,
2–5 cm long, 0.7–1.5 cm wide, densely scaly glandular punctate, sparsely pub-
escent, base cuneate, apex acuminate. Racemes much flowered, globose or sub-
globose; rachis shorter than leaf, densely scaly glandular punctate, villous when
young; bracts lanceolate, 6–7 mm, densely glandular punctate. Calyx campanulate,
ca. 5 mm, sparsely scaly glandular punctate and pubescent, 5-toothed, upper 2 teeth
partly joined. Corolla purple; standard narrowly ovate or elliptic, 6–9 mm, very
shortly clawed; wings 5–6 mm; keel slightly shorter than wings, clawed, auriculate.
Pod dense, narrowly ovoid, 12–18 mm long, 4–6 mm wide, densely spiny, apex
cuspidate. Seeds brown, ca. 4 mm.
Glycyrrhiza lepidota Pursh The plant reproduces by seed and underground stems
called rhizomes. Licorice grows 1.5–3.5 ft tall (0.5–1.0 m). The stems are smooth,
erect, and branched. The leaves are smooth, alternately attached to the stem, and
have many (7–21) leaflets (odd-pinnate) that are arranged opposite each other along
the leaf stem. The flowers are on short stalks and crowded on terminal spikes. Its
flowers are yellowish white and shaped similar to alfalfa flowers. Flowers bloom in
June to August and seed matures from July to October. The seed pods are brown,
leathery, and half to 1.0 inch long (1.25–2.54 cm). The pods are covered with many
stout, hooked, brown spines which form a bur. This hooked pod assists the plant in
10 2 Botany

dispersal since they stick to animal fur and are moved to new sites. Seeds are green
to reddish brown, smooth and bean shaped. This plant is found on sites that range
from moist to moderately dry, usually in rich soils. This plant can be located along
streams, in grasslands, along roadsides and railway right-of-ways in sites that have
suffered mild disturbance.
Glycyrrhiza eglandulosa X. Y. Li Herbs, perennial. Roots and rhizomes strong.
Stem 50–90 cm tall, sparsely brown glandular punctate, prickly, white hairy.
Leaves 15–22 cm, 11–15-foliolate; petiole sparsely glandular, prickly, white hairy;
leaflets ovate or elliptic, 2.3–4.5  0.6–1.4 cm, adaxially sparsely puberulent,
densely brown glandular, base rounded or slightly cordate, margin undulate, apex
obtuse. Racemes 11–19 cm, ca. as long as or longer than leaves, sparsely glandular,
prickly, hairy; bracts lanceolate, white hairy. Calyx campanulate, 9–10 mm, den-
sely brown glandular punctate and pilose; upper 2 teeth nearly joined completely.
Corolla 1.2–1.6 cm; standard narrowly elliptic, 13–15  3–5.5 mm, base shortly
clawed; wings oblong, ca. 6.5  1.9–2.5 mm, claw linear, auriculate. Ovary
straight, densely puberulent. Legume zigzag, oblong, flat, 12–30  5–7 mm,
pilose. Seeds 1–9. Fl. June–August, fr. July–October. Sandy areas, grasslands on
hills; 300–2000 m.
Glycyrrhiza pallidiflora Maxim. Herbs, perennial. Stem 1–1.5 m tall, striped,
densely yellow-brown scaly glandular punctate, nearly glabrous. Leaves 6–20 cm,
9–15-foliolate; stipules lanceolate, ca. 5 mm; petiole glabrous, densely glandular
punctate; leaflets lanceolate or ovate-lanceolate, 2–6  1.5–2 cm, glabrous, den-
sely scaly glandular punctate, base cuneate, margin serrulate, apex acuminate with
mucro. Racemes much flowered, oblong or globose; rachis shorter than leaves,
densely brown glandular punctate and pubescent; bracts ovate-lanceolate, 6–8 mm,
membranous, glandular punctate. Calyx campanulate, 4–5 mm, densely glandular
punctate and sparsely pubescent at base, lanceolately 5-toothed. Corolla light
purple, purple, or purple-red; standard ovate, 6–8 mm, base shortly clawed,
apex rounded; wings 5–6 mm; keel shorter than wings. Legume ovoid,
10–17  6–8 mm, rigidly spiny, apex abruptly acuminate. Seeds 2, black, ca.
2 mm. Fl. June–July, fr. July–September. Riverbanks, open valleys by streams,
open slopes, margins of farms, roadsides; 2600–3100 m.
Glycyrrhiza squamulosa Franch. Herbs, perennial. Roots and rhizomes slender.
Stem 30–60 cm tall, densely yellow scaly glandular punctate, glabrous or sparsely
pubescent. Leaves 5–15 cm, 9–13-foliolate; stipules lanceolate, 2–3 mm, sparsely
white pubescent, glandular punctate; petiole densely scaly glandular punctate,
sparsely pubescent; leaflets narrowly elliptic to oblong-obovate, densely scaly
glandular punctate, base cuneate, margin serrulate, apex usually retuse. Racemes
much flowered; rachis longer than leaves, densely scaly glandular punctate, spar-
sely pubescent; bracts lanceolate, membranous, glandular punctate, pubescent.
Calyx campanulate, 2.5–3.5 mm, densely scaly glandular punctate, sparsely pub-
escent, 5-toothed; upper 2 teeth slightly joined. Corolla white, abaxially densely
yellow glandular punctate; standard ovate-oblong, 5–7  2.5–3.5 mm; wings
2.1 Taxonomy and Morphology 11

4–5 mm; keel straight, slightly shorter than wings. Legume brown, orbicular or
broadly reniform, 5–10  4–7 mm, tuberculate, apex mucronate. Seeds 2, green,
ca. 2 mm. Fl. May–July, fr. June–September. Roadsides, wastelands; 100–1100 m.
Glycyrrhiza uralensis Fisch. Herbs, perennial. Roots and rhizomes strong. Stem
30–120 cm tall, densely scaly glandular punctate and white or brown tomentose.
Leaves 5–20 cm, 5–17 foliolate; stipules triangular-lanceolate, ca. 5  2 mm,
densely white pubescent; petiole densely brown glandular punctate and pubescent;
leaflets ovate, narrowly ovate, or orbicular, 1.5–5  0.8–3 cm, densely glandular
punctate and pubescent, base rounded, margin entire or repand, apex obtuse and
mucronate. Racemes much flowered; rachis shorter than leaf, densely brown
glandular punctate and pubescent; bracts brown, oblong-lanceolate, 3–4 mm,
membranous, yellow glandular and pubescent. Calyx campanulate, 7–14 mm,
densely yellow glandular punctate and pubescent, inflated to saccate at base,
5-toothed; upper 2 teeth mostly joined. Corolla purple, white, or yellow, 1–2.4 cm;
standard oblong, base shortly clawed, apex retuse; wings shorter than standard; keel
shorter than wings. Ovary densely glandular. Legume falcate to curved into a ring,
densely tuberculate and glandular hairy. Seeds 3–11, dark green, orbicular or
reniform, ca. 3 mm. Fl. June–August, fr. July–October. Sandy lands, dry river-
banks, grasslands on hills; 400–2700 m.
Glycyrrhiza inflata Batalin Herbs, perennial. Roots and rhizomes strong. Stem
50–150 cm tall, woody at base. Leaves 4–20 cm, 3–7(or 9)-foliolate; stipules
caducous, brown, triangular-lanceolate, small, ca. 1 mm; petiole densely brown
glandular punctate, densely pubescent when young; leaflets ovate, elliptic, or
oblong, 2–6  0.8–3 cm, brown glandular punctate, sparsely pubescent on veins,
base rounded, margin somewhat undulate, apex acute or obtuse. Racemes with
rachis shorter than or ca. as long as leaves, densely glandular punctate, densely
hairy when young; bracts oblong-lanceolate, ca. 3 mm, densely glandular punctate
and pubescent. Calyx campanulate, 5–7 mm, densely glandular punctate and
pubescent, 5-toothed; upper 2 teeth joined to half from base. Corolla purple or light
purple; standard narrowly elliptic, 6–9(−12)  4–7 mm, base shortly clawed, apex
rounded; wings ca. as long as standard, obviously auriculate and clawed; keel
shorter, auriculate and clawed. Legume straight or slightly curved, elliptic or
oblong, 8–30  5–10 mm, inflated or somewhat constricted between seeds, brown
glandular punctate and glandular hairy, sparsely villous. Seeds 1–4, green, orbic-
ular, 2–3 mm in diam. Fl. May–July, fr. June–October. Riverbanks, dry stream
banks, margins of farms, wastelands; ca. 1100 m.
Glycyrrhiza bucharica Regel Perennial; stem tall, 80–100 cm, firm, straight,
usually branching, more or less glandular; stipules small, deciduous at flowering;
petioles 2–5 cm long, more or less glandular; leaves 6–15(20) cm long, ternate,
rarely imparipinnate, with 2 pairs of leaflets; leaflets elongate, oblong-lanceolate,
obtuse, cuneate or rounded-cuneate at base, 4–6 cm long, 1.5–2 cm wide, more or
less densely covered with viscid glands on both sides. Floral racemes rather poor,
4–8 cm long; peduncles glandular and sparsely hairy, 2–4 cm long; flowers small
12 2 Botany

5–7 mm long; calyx campanulate, ca. 2.5–3 mm long, more or less densely glan-
dular, with broad triangular teeth short-ciliate at margin and much shorter than tube;
corolla white; standard with limb broadly rhombic-ovate, obtuse, very
short-clawed; pods erect, oval oblong-oval, sometimes subglobular, more or less
laterally compressed, 1–2 cm long, 0.7–1 cm wide, dehiscent (valves white inside),
densely covered with viscid, often reddish glands, sometimes with sparse thin and
pale brittle bristles, 1–2 seeded, June–August.
Glycyrrhiza gontscharovii Maslenn. Perennial; stems 70–100 cm high, few,
branching, glabrous, with scattered glands; leaves 10–16 cm long, petioles and
rachis sparsely covered with short hairs and glands; leaflets 3–4 paired,
short-petioluled (3–4 mm), oblong-ovate or oblong-lanceolate, 2.5–5.5 cm long,
1–1.8 cm wide, glabrous but densely glandular. Racemes loose, many-flowered, on
peduncles much shorter than leaves; flowers 1(2) on 1–1.5 mm long pedicels; calyx
campanulate, 3–4 mm long, densely glandular, short-hairy, teeth triangular, acute,
2–2.5 mm long, sparsely long ciliate at margin; corolla lilac in bud, whitish yel-
lowish with faint lilac tint; standard 9–10 mm long, limb triangular-ovate, slightly
attenuate and gradually tapering in upper part, rounded at apex, claw much shorter
than limb; wings 8–9 mm long, limb oblong, twice as long as claw; keel 6–7 mm
long, acute; pods indehiscent, oval, attenuate–acuminate, 13–15 mm long, 7–8 mm
wide, laterally somewhat compressed, densely covered with short acute bristles
thickened below; seeds flat, oval-reniform, smooth, dark gray-green. June–July.
Stony river valleys, 800–1000 m.
Glycyrrhiza korshinskyi Grig Perennial; stems erect or ascending, branching or
simple, 30–70 cm high, more or less densely covered with viscid brown glands,
rarely with short glandular prickles, glabrous or rarely with scattered hairs in upper
part; stipules deciduous at flowering; leaves 5–12 cm long, with short, more or less
glandular (like rachis) petioles; leaflets 2–5 paired, broadly elliptic, ovate or obo-
vate, ca. 1–3 cm long, 0.6–2.5 cm wide, densely glandular on both sides but mainly
beneath, often viscid of the resinous excretions. Racemes rather loose, (1) 2–6 cm
long; peduncles and axis of inflorescence more or less glandular and sometimes
short-hairy; flowers 10–13(14) mm long; calyx 4–7 mm long, glandular, sometimes
sparsely hairy, teeth as long as tube or slightly shorter, two upper teeth much less
cut than the others; corolla violet-white; limb of standard ovate, gradually tapering
into claw; pods oblong, 1–3 cm long, 4–7 mm wide, more or less falcately curved,
transversely sinuate-torulose (when viewed from side of sutures), densely beset
with brown glands or short glandular prickles. June–July.
Glycyrrhiza triphylla Fisch. & C. A. Mey Perennial erect herb or undershrub, c.
30–60 cm tall, branches puberulous and dotted with yellow glands. Stipules free
lateral, c. 2.5 mm long, caducous. Leaf palmately trifoliolate, rarely pinnately
5-foliolate, petiole c. 6–14 mm long, petiolule up to 1 mm, lamina c. 5–21 mm
long, c. 3.5–17 mm broad, obovate, emarginate, glabrous above, puberulous below,
glandular punctate on both sides. Inflorescence a peduncled axillary raceme;
peduncle c. 17–45 mm long. Bract c. 1.5 mm long, ciliate at the margin, caducous.
2.1 Taxonomy and Morphology 13

Pedicel c. 1 mm long, glandular punctate. Calyx c. 3 mm long, glandular punctate,

teeth c. 1.5 mm long. Corolla white. Vexillum c. 5–6 mm long. Wing c. 4.5–5 mm
long. Keel 4.0–4.5 mm long. Fruit c. 15–23 mm long, c. 5–8 mm broad, covered
with hard spiny tubercles, 2–6-seeded. May–June.

2.2 Pollen Studies

Pollen characters have been used much to enlighten the relationship among different
taxa. As far Glycyrrhiza, very few taxa have been examined using light microscope
(Li 1992). Latter has studied the pollen grains of five Glycyrrhiza taxa with the help of
light microscope. He has reported that the exine sculpture of pollen grains is mainly
reticulated. No major infrageneric variations have been determined. However, Meng
and Zhu (2010) have studied the Glycyrrhiza pollen grains in eleven species in detail
using scanning electron microscope (SEM). The size of pollen grains has been
recorded as 24.47–33.18  23.82–31.83 lm; the shape is prolate spheroidal with
perforate, perforate to rugulate, rugulate, and foveolate exine sculpture, being
3-colporate and radially symmetrical. The colpi are usually long, broad, with irregular
magrin; aperture membranes are granular or verrucate in some taxa; polar apex is flat
or obtuse; and exine sculpture becomes faint or disappears at the top. In all, two types
of pollen grains have been recorded: trilobed-circular and subtriangular in polar view.
In Glycyrrhiza echinata, G. squamulosa, G. pallidiflora, and G. yunnanensis pollen
grains are trilobed-circular in polar view but others are subtriangular in polar view
(Meng and Zhu 2010). These pollen investigations depict that pollen shape, size, and
exine sculpture are variable in Glycyrrhiza genus. It can provide some taxonomic
support for existing classification. The shapes in polar view show high taxonomic
value among the species investigated by these workers. In four species, G. echinata,
G. squamulosa, G. pallidiflora, and G. yunnanensis, the pollen grains are tricolporate,
with perforate to rugulate exine sculpture and trilobed-circular in polar view. In
G. aspera, G. glabra, G. inflata, G. uralensis, G. foetida, G. astragalina, and
G. acanthocarpa, they are subtriangular in polar view. G. aspera, G. glabra,
G. inflata, and G. uralensis have similar exine sculptures but G. foetida,
G. astragalina, and G. acanthocarpa have distinctive exine sculptures (Meng and
Zhu 2010).
Glycyrrhiza astragalina, distributed in Argentina and Chile, has a rugulate exine
sculpture, whereas G. acanthocarpa, from South Australia, has a foveolate exine
sculpture (Meng and Zhu 2010). Kruganova (1955) has placed the two species G.
acanthocarpa and G. astragalina in section Pseudoglycyrrhiza, together with G.
echinata, G. squamulosa, and G. pallidiflora. However, the exine sculpture and the
shape in polar view of the two species G. astragalina and G. acanthocarpa differ
from that of G. echinata, G. squamulosa, and G. pallidiflora (Meng and Zhu 2010).
Meng and Zhu (2010) have also noticed that the two species have unique
morphological and geographical characters, and therefore they do not agree to
simply put the two species into the same group with the three species G. echinata,
14 2 Botany

Table 2.1 Distribution of some taxa of the genus Glycyrrhiza (Duran et al. 2014)
Taxa Country and/or geographic region
Glycyrrhiza Australia
acanthocarpa
Glycyrrhiza aspera Afghanistan, Azerbaijan, China, Georgia, Iranian, Kazakhstan,
Kyrgyzstan, Mongolia, Russia, Tajikistan, Turkmenistan, Uzbekistan,
Lebanon–Syria
Glycyrrhiza Turkey (Endemic)
asymmetrica
Glycyrrhiza Afghanistan, Tajikistan, Turkmenistan, Uzbekistan
bucharica
Glycyrrhiza Turkey, Armenia, Azerbaijan, Georgia, Iranian, Kazakhstan, Russia,
echinata Nakhchivan, Bulgaria, Former Yugoslavia, Greece, Hungary, Italy,
Moldova, Romania, Ukraine, Israel, Lebanon, Syria
Glycyrrhiza China
eglandulosa
Glycyrrhiza Turkey (Endemic)
flavescens
ssp. flavescens
Glycyrrhiza Turkey (Endemic)
flavescens
ssp. antalyensis
Glycyrrhiza foetida Algeria, Morocco, Tunisian, Spain
Glycyrrhiza Azerbaijan, Georgia, Russia, Moldova, Ukraine, Algeria, Egypt, Libya
foetidissima
Glycyrrhiza glabra Asia, European, America, Australia
Glycyrrhiza Tajikistan (Endemic)
gontscharovii
Glycyrrhiza Turkey (Endemic)
iconica
Glycyrrhiza inflata China, Kazakhstan, Kyrgyzstan, Mongolia, Tajikistan, Turkmenistan,
Uzbekistan
Glycyrrhiza China, Kazakhstan, Russia
korshinskyi
Glycyrrhiza America
lepidota
Glycyrrhiza China, Mongolia, Russia
pallidiflora
Glycyrrhiza China, Mongolia
squamulosa
Glycyrrhiza Afghanistan, Iranian, Kazakhstan, Pakistan, Turkmenistan, Uzbekistan
triphylla
Glycyrrhiza Afghanistan, Kazakhstan, Kyrgyzstan, Mongolia, Pakistan, Russia,
uralensis Tajikistan
Glycyrrhiza China
yunnanensis
2.2 Pollen Studies 15

Table 2.2 Comparison of the number of species belonging to the genus Glycyrrhiza on country
basis (Duran et al. 2014)
Country Total species number
Asia Russia 12
China 8
Mongolia 7
Turkey 6
Tajikistan 6
Afghanistan 5
Azerbaijan 5
Turkmenistan 5
Uzbekistan 5
Iranian 4
Georgia 4
Kazakhstan 4
Kyrgyzstan 4
Pakistan 3
Lebanon–Syria 3
Syria–Palestine 3
Israel–Jordan 2
Armenia 2
Iraq 1
India 1
Maldives 1
Sardinia 1
Africa Algeria 3
Morocco 1
Tunisian 1
Libya 1
Egypt 1
European Ukraine 3
Bulgaria 2
Former Yugoslavia 2
Greece 2
Italy 2
Moldova 2
Romania 2
Spain 2
Albania 1
Austria 1
Cretan 1
Czech Republic 1
(continued)
16 2 Botany

Table 2.2 (continued)

Country Total species number
France 1
Hungary 1
Sicily 1
Portugal 1
Swiss 1
Cyprus 1
America 3
Australia 2

G. squamulosa, and G. pallidiflora. Further studies are needed to confirm the

systematic status of G. astragalina and G. acanthocarpa within the genus
Glycyrrhiza (Meng and Zhu 2010).

2.3 Distribution in the World

It is distributed in Mediterranean Europe (native in Sardinia, Italy, Sicily, Albania,

Greece, Bulgaria, and Romania) France, Spain, and eastern Mediterranean countries
Syria, Lebanon, Palestine, Jordan, and Turkey. The distribution extends to Iran,
Iraq, Caucasus, Afghanistan, W. Siberia, C. Asia, and Northern India (Tables 2.1
and 2.2). It is cultivated in Russia, UK, USA, Italy, France, Germany, Spain, China,
Pakistan, and India. Large-scale commercial cultivation is seen in Spain, Sicily, and
England (Warrier et al. 1994; Batanouny et al. 1999; Irani et al. 2010; Vispute and
Khopade 2011).

References

Altay V, Karahan F, Öztürk M, Hakeem KR, Ilhan E, Erayman M (2016) Molecular and
ecological investigations on the wild populations of Glycyrrhiza L. taxa distributed in the East
Mediterranean Area of Turkey. J Plant Res 129(6):1021–1032
Batanouny KH, Aboutabl E, Shabana M, Soliman F (1999) Wild medicinal plants in Egypt (with
contribution of: Aboutabl E, Shabana M, Soliman F). Chapter Two—“Pharmacopoeial Wild
Medicinal Plants in Egypt” With support of the Swiss Development Co-operation (SDC).
Academy of Scientific Research and Technology, Egypt. The World Conservation Union
(IUCN), Switzerland, pp 60–64
Bell LW, Bennett RG, Ryan MH, Clarke H (2010) The potential of herbaceous native Australian
legumes as grain crops: a review. Renewable Agric Food Syst 26(1):72–91
Bremer B, Bremer K, Chase M, Fay M, Reveal J, Soltis D et al. (2009) An update of the
Angiosperm Phylogeny Group classification for the orders and families of flowering plants:
APG III. Bot J Linn Soc
References 17

Davis PH (1970) Flora of Turkey and the East Aegean Islands, vol 3. Edinburgh University Press,
Edinburgh, pp 260–263
Duran A, Küçüködük M, Dündar E, Martin E, Çetin O, Çelik M, Gürbüz Y (2014) Türkiye
Glycyrrhiza L. (meyan) cinsinin morfolojik, palinolojik, sitotaksonomik, moleküler filogenetik
kapsamda incelenmesi ve glycrrhizin üretiminde anahtar rolü olan b-amyrin 11-oksidaz
geninin moleküler analizi. TUBITAK - Proje no: 110T949. (In Turkish)
Fiore C, Eisenhutb M, Ragazzic E, Zanchind G, Armanini D (2005) A history of the therapeutic
use of liquorice in Europe. J Ethnopharmacol 99:317–324
Irani M, Sarmadi M, Bernard F, Ebrahim GH, Bazarnov HS (2010) Leaves antimicrobial activity
of Glycyrrhiza glabra L. Iranian Journal of Pharmaceutical Research 9(4):425–428
Karaca S (1992) Muş ve Izmir yöresinde doğal yayılış gösteren Glycyrrhiza glabra L. bitkisinin
anatomik yapı farklılıkları üzerinde bir inceleme [An investigation on the anatomical
differences of Glycyrrhiza glabra L. showing natural distribution in the environs of Muş and
İzmir (Turkey)]. Ege Universitesi Fen Bilimleri Enstitüsü, Yüksek Lisans Tezi, Izmir-Turkey
Komarov, V.L. (ed.). 1933–1964. Flora of the USSR. Vol. 1-30. Keter Press, Moscow
Kruganova EA (1955) A review of species from the genera Glycyrrhiza L. and Meristotropis
Fisch. et Mey. Acta Instituti Botanici 11:161–197
Li X-Y (1992) Studies on germplasm of Glycyrrhiza by using different taxonomic methods. Adv
Plant Taxonomy Northwest China 1:7–24
Meng L, Zhu X-Y (2010) Palynological characters of Glycyrrhiza, Glycyrrhizopsis, and
Meristotropis (Leguminosae), with special reference to their taxonomic significance. J Syst
Evol 48(6):455–463
Nomura T, Fukai T, Akiyama T (2002) Chemistry of phenolic compounds of licorice (Glycyrrhiza
species) and their estrogenic and cytotoxic activities. Pure Appl Chem 74:1199–1206
Sofia H, Walter TM (2009) Review of Glycyrrhiza glabra Linn. Siddha Papers, Med J 2(1):1–7
Sümbül H, Tufan O, Düşen OD, Göktürk RS (2003) New taxon of Glycyrrhiza L. from southwest
Anatolia. Israel J Plant Sci 51:71–74
Vispute S, Khopade A (2011) Glycyrrhiza glabra Linn.-“Klitaka”: A review. Int J Pharma Bio Sci
2(3):42–51
Warrier PK, Nambiar VPK, Ramankutty C (1994) Indian Medicinal Plants. Madras, Orient
Longman
Chapter 3
Ecology

The plant generally prefers various habitats such as cultivated fields (wheat and
olive grown areas), water channels, roadsides, stony areas, alluvial river valleys,
sand dunes, sandy or clayey soil types (Fig. 3.1), and subtropical climate between 0
and 1087 m altitudes (Davis 1970; Oğuz 1972; Akan and Balos 2008). Latter
depicts its wide ecological amplitude. It grows on fertile soils up to a height of
2.5 m (Anilkumar et al. 2012).
Glycyrrhiza glabra shows high salt tolerance and flourishes under wide range of
soil salinity conditions (Mirkin et al. 1971). Rao (1993) has reported
drought-resistant variety of G. glabra from the floodplains of river Amudarya.
Hayash et al. (2003) have recorded the highest yield of roots and top growth in
Golodnaya steppe and Amudarya populations of liquorice in chloride sulfate soils
of Uzbekistan. The plant develops good symbiotic relationship with certain soil
bacteria such as Mesorhizobium tianshanense, Rhizobium giardinii, and Rhizobium
leguminosarum (Li et al. 2012) and these bacteria form nodules on the roots and fix
atmospheric nitrogen. Some of this nitrogen is utilized by the growing plant but
some can also be used by other plants growing nearby (Rogers 2014).
In Turkey, Glycyrrhiza asymmetrica is distributed among macchias as well as
Pinus brutia forests in the Mediterranean region of Turkey, flourishing on soils rich
in humus, while Glycyrrhiza flavescens grows among the macchia areas on rich
calcareous soils. The habitat preferences of G. glabra and Glycyrrhiza echinata are
same and/or similar (Baytop 1952; Davis 1970; Oğuz 1972).
The root and rhizome structure of the taxa in the Glycyrrhiza genus is highly
developed. The root grows down up to 7 m (Oğuz 1972). G. glabra also prefers
sandy soils and rhizomes are usually vertical. The rhizomes in loamy or slightly
clayey soils are stretching horizontally. A single plant can grow from a bud on the
rhizome in G. glabra. Usually, the rhizome bears more than one bud in G. echinata
(Oğuz 1972). According to Oğuz (1972), rhizomes are generally found in vertical
styles in G. asymmetrica and G. flavescens, which grow especially on soils rich in
humus. In both species, rhizomes and roots are fairly thick. The investigations
carried out by İlhan et al. (2016) reveal that analysis of the soils supporting
Glycyrrhiza iconica in Turkey is generally loamy with a pH value of 7.93. They
usually contain 2.47% organic matter, 0.0122% total nitrogen, 0.0022% phos-
phorus, 22.86% CaCO3, and 0.31% potassium.
According to Altay et al. (2016), the results of physical and chemical analysis of
the soil samples of Glycyrrhiza taxa collected from the research area depict that

© The Author(s) 2017 19

M. Öztürk et al., Liquorice, SpringerBriefs in Plant Science,
https://doi.org/10.1007/978-3-319-74240-3_3
20 3 Ecology

Fig. 3.1 Habitat preferences of G. glabra in Turkey (1: Cultivated ground; 2: water channels 3–5:
roadside; 6: sand dunes)

G. glabra var. glandulifera generally prefers clayey loam, loamy, clayey, and heavy
clayey soils. Soil pH ranges between 7.72 and 8.52, EC between 87 and 665
(lS cm−1), calcium carbonate between 1.41 and 4.81(%), organic matter between
0.52 and 3.44 (%), nitrogen between 0.03 and 0.17 (%), phosphorus between 1.18
and 31.91(mg kg−1), sodium between 20.01 and 400.1 (mg kg−1), and potassium
between 28.85 and 583.8 (mg kg−1).
The results of the analysis of G. glabra var. glandulifera of roots, stems, and
leaves collected during flowering season show that on dry weight basis, the nitrogen
values range between 1.20 and 1.94 (%), phosphorus between 7.89 and 13.27
(mg kg−1), sodium between 2.97 and 16.07 (mg kg−1), and potassium between
17.46 and 61.95 (mg kg−1) in roots. In the stems, the nitrogen values range between
0.52 and 1.10 (%), phosphorus between 18.23 and 34.49 (mg kg−1), sodium
between 9.83 and 23.20 (mg kg−1), and potassium between 52.11 and 91.64
(mg kg−1). In the leaves, the nitrogen values range between 2.16 and 3.18 (%),
phosphorus between 16.99 and 38.20 (mg kg−1), sodium between 7.21 and 33.69
(mg kg−1), and potassium between 34.05 and 56.02 (mg kg−1).
The soil analysis of G. flavescens ssp. flavescens reveals that it generally prefers
clayey and heavy clayey soils with a soil pH of 7.13–7.82 and EC 115–381 (lS/cm).
The values for calcium carbonate, organic matter, nitrogen, phosphorus, sodium and
potassium vary between 0.92–2.92 (%), 0.92–5.66 (%), 0.04–0.28 (%), 1.76–11.24
(mg kg−1), 31.52–129.5 (mg kg−1), and 26.45–158.4 (mg kg−1) respectively.
In G. flavescens ssp. flavescens, the root analysis data shows that nitrogen values
range between 1.71 and 2.70 (%), phosphorus between 5.40 and 25.59 (mg/kg),
sodium between 5.24 and 15.67 (mg/kg), and potassium between 22.74 and 66.17
(mg/kg).
3 Ecology 21

In the stems, nitrogen ranges between 1.74 and 3.19 (%), phosphorus between
20.61 and 60.51 (mg/kg), sodium between 12.43 and 23.20 (mg/kg), and potassium
77.20 and 134.0 between (mg/kg).
The leaf analysis results reveal that nitrogen values lie between 2.60 and 5.85
(%), phosphorus between 19.89 and 49.32 (mg/kg), sodium between 5.89 and 20.32
(mg/kg), and potassium between 36.51 and 68.72 (mg/kg) values on dry weight
basis.
G. echinata generally prefers heavy clayey soils. The soil pH changes between
8.46 and 8.54, EC between 197 and 293, (lS cm−1), calcium carbonate between
1.12 and 2.34 (%), organic matter between 2.38 and 2.42 (%), nitrogen between
0.11 and 0.13 (%), phosphorus between 7.15 and 14.11, (mg kg−1), sodium from
50.02 to 111.5 (mg kg−1), and potassium between 77.35 and 164.0 (mg kg−1).
The nitrogen in the roots ranges between 1.50 and 1.72 (%), phosphorus
between 7.05 and 9.81(mg kg−1), sodium between 5.81 and 20.35 (mg kg−1), and
potassium between 28.62 and 48.83 (mg kg−1).
The values in stems lie between 0.82–0.90 (%) for nitrogen, 20.04–20.69
(mg kg−1) for phosphorus, 10.27–12.60 (mg kg−1) for sodium, and for potassium
66.39–76.96 (mg kg−1).
In the leaves, the values vary between 3.43 and 3.70 (%) for nitrogen, 17.84 and
42.78 (mg kg−1) for phosphorus, 5.75 and 17.32 (mg kg−1) for sodium, and 46.35
and 51.86 (mg kg−1) for potassium on dry weight basis.

References

Akan H, Balos M (2008) GAP Bölgesi’nden toplanan meyan kökü (Glycrrhiza glabra L.)
taksonunun ihracat durumu, etnobotanik özellikleri ve tıbbi önemi. Fırat Üniversitesi Fen ve
Mühendislik Bilimleri Dergisi 20(2):233–241 (In Turkish)
Altay V, Karahan F, Öztürk M, Hakeem KR, Ilhan E, Erayman M (2016) Molecular and
ecological investigations on the wild populations of Glycyrrhiza L. taxa distributed in the East
Mediterranean Area of Turkey. J Plant Res 129(6):1021–1032
Anilkumar D, Joshi H, Nishteswar K (2012) Review of Glycyrrhiza glabra (Yastımadhu)–a broad
spectrum herbal drug. Pharma Sci Monit 3(4):3171–3195 ISSN: 0976-7908
Baytop T (1952) Anadolu meyankökü ve meyanbalı üzerinde farmakognostik araştırmalar.
Doçentlik Tezi. Ist. Univ. Ecz. Fak. Istanbul-Turkiye
Davis PH (1970) Flora of Turkey and the East Aegean Islands, vol 3. Edinburgh University Press,
Edinburgh, pp 260–263
Hayash H, Hattori S, Inoue K, Khodzhimatov O, Ashurmetov O, Ito M, Honda G (2003) Field
survey of Glycyrrhiza plants in Central Asia: chemical characterization of G. glabra collected
in Uzbekistan. Chem Pharm Bull 51(11):1338–1340
İlhan V, Dural H, Temel M (2016) Anatomical, morphological and ecological the study on
Glycyrrhiza iconica Hub.-Mor. (Fabaceae). Turkish J Life Sci 1(1):23–33
22 3 Ecology

Li L, Sinkko H, Montonen L, Wei G, Lindström K, Räsänen LA (2012) Biogeography of

symbiotic and other endophytic bacteria isolated from medicinal Glycyrrhiza species in China.
FEMS Microbiol Ecol 79(1):46–68
Mirkin BM, Antipov EA, Sangitov SI (1971) Rastit Resur. 7(3):417–420
Oğuz G (1972) Türkiye Glycyrrhiza L. türleri ile ilgili morfolojik ve taksonomik bir araştırma.
Doktora tezi, Ege Üniversitesi Fen Fakültesi İlmi Raporlar Serisi No 114–1972, Izmir-Türkiye
Rao KVS (1993) A review on Licorice. Ancient Sci Life XIII(1–2):57–88
Rogers M (ed) (2014) Licorice. In: Herbalpedia. http://www.herbalpedia.com
Chapter 4
Ecophysicological Aspects

Abd El-Rahman et al. (1974) have shown that Glycyrrhiza glabra grows under
severe climatic conditions and adverse moisture supply and inhabits different types
of soils. The amount of available soil moisture to the plant is a factor of paramount
importance in the plant life in arid zones, which varies in different localities sup-
porting the plant. He studied it after planning to cultivate some economic plants in
desert and semidesert areas in Egypt. It seems necessary to study the water relations
of these plants including G. glabra. Their investigation deals with the water rela-
tions of this plant, comprising studies on the transpiration, osmotic pressure and
water saturation deficit in two localities, namely Burg El Arab and Wadi El Natrun
in Egypt. The first is a locality in the Western Mediterranean coastal region and the
second represents a site on the escarpment bordering Wadi El Natrun depression in
the Lybian desert (Abd El-Rahman et al. 1974). They conducted transpiration
measurements which show that the plant transpires at relatively higher rates than
desert plants. The curves of diurnal march of the transpiration and those of the
stomatal aperture showed almost the same trend, indicating a strong stomatal
control on transpiration. The plant exhibits high values of osmotic pressure and
water saturation deficit which increase by the progress of the growing season. These
values are higher in the locality with relatively low available soil moisture. The
plant has been found to withstand high water deficits for long periods.
Siyamoğlu (1984) have published some data on the composition of liquorice
(G. glabra) roots from Anatolia. The average values published by them are as
follows: pH: 5.58; 8.55 for moisture; 91.44 g/100 g for dry matter; 1.25 for total
nitrogen, 7.85 for protein, 23.55 for cellulose, 16.38 for total sugar, 9.15 for
reducing sugars, 7.59 for ash, 1.79 for calcium, 0.073 for phosphorus, 0.0627 for
iron, 24.78 for cold water extract, 25.33 for hot water extract, 8.50 for glycyrrhizic
acid, 2.9 for fructose, 2.1 for glucose, and 10.2 for sucrose (g/100 g in dry matter).
Liquorice (G. glabra) is regarded as a salt-tolerant plant. It can be used for
remediation of degraded saline habitats, which in turn could serve as an alternative
income source for farmers in some saline arid areas of the world (Abe et al. 2005;
Kushiev et al. 2005; Lu et al. 2013). Its deep root goes down up to 17 m and can
therefore reach deep ground water. The yield of fresh roots on 3 years growth basis
has been reported to lie around 10–15 t/ha. The fusiform root system of this species
possesses large number of suckers, each over 1 m long (Kushiev et al. 2005). Many
reports published on the use of G. glabra in the saline soil reclamation stress that

© The Author(s) 2017 23

M. Öztürk et al., Liquorice, SpringerBriefs in Plant Science,
https://doi.org/10.1007/978-3-319-74240-3_4
24 4 Ecophysicological Aspects

these areas after restoration can be evaluated for irrigated cropping systems
(Kerbabaev 1971; Badalov 1996). According to Lu et al. (2013), an increase in the
proline synthesis in this plant follows immediately after an increased uptake of K+,
Ca+2, and Mg+2 under increasing NaCl concentrations. The proline synthesis leads
to an increase in its osmoregulation ability and plant shows adaptation to high saline
environment. Kushiev et al. (2005) have investigated the potential use of G. glabra
for the remediation of abandoned saline areas during 4 years. These areas have been
returned to a cotton/wheat crop rotation. Their results have demonstrated that
aboveground biomass values were 3.55 t/ha during the first year, followed by
5.6 t/ha in the second year, and finally 8.55 t/ha during the third year. They also
report that where total dissolved salt (TDS) of the groundwater in the control plot
increased from 5.19 to 6.11 g l−1, the plots under liquorice showed a decrease over
the same period from 6.35 to 3.99 g l−1. This signifies that this species has an
ability to reclamate the saline soils. Moreover, in the fields under liquorice culti-
vation, the Mg+2, Ca+2, SO42−, N+, and Cl− have shown a marked decline as
compared to the fields without liquorice (Kushiev et al. 2005). These findings
enlighten the fact that in the fields with liquorice cultivation, salt content decreases
over a period of 3 years from 215 to 185 t/ha in the top 2 m depth of soil. The
cotton and wheat cultivation following liquorice shows an increase in the yield
(Kushiev et al. 2005; Egamberdieva and Mamedov 2015).
Srivastava et al. (2013) have developed a protocol for slow growth conservation.
Spectacular success has been achieved in preserving shoot apices of G. glabra
under slow growth conditions. Cultures have responded best, when incubated at
10 °C under low light intensity (2.5 lmol m−2 s−1 quantum flux density) and
sealed with polypropylene caps. The optimized nutrient formulation to maintain
slow growth of cultures contained 5.0 mg L−1 ancymidol and 0.1 mg L−1 abscisic
acid. The high osmoticum of nutrient medium has been achieved by employing
1.0 mg L−1 polyethylene glycol, where cultures could be conserved up to 6 months
without any subculture. A very low concentration of BA (0.1 mg L−1) and IAA
(0.05 mg L−1) has proved beneficial for retrieval of the conserved shoots. Among
different combinations of osmotic agents (sucrose, sorbitol and mannitol), used for
increasing the subculture period, 20 g L−1 of mannitol has suited best for slow
growth conservation with only one subculture in a year. Shoots have exhibited
100% survival and complete retrieval after conservation. Half-strength modified
MS medium with 0.25 mg L−1 BA, 1.0 mg L−1 IAA, and 10 mg L−1 B-9 along
with 10 mg L−1 AdS has proved beneficial for shoot growth, foliage development
as well as rooting of shoots. The in vitro raised plantlets have shown 100%
transplant success (Srivastava et al. 2013).
Egamberdieva and Mamedov (2015) have found that Glycyrrhiza uralensis can
germinate at potting soil irrigated with 50 and 100 mM NaCl nutrient solution.
However, 100 mM NaCl concentration totally inhibited plant growth after 1–
2 weeks. They also observed that shoot dry weight and length as well as N uptake
and nodulation of G. uralensis were clearly improved when the plant was inocu-
lated with its salt-tolerant PGPR strains compared with the uninoculated plants
irrigated with 75 mM NaCl. Lu et al. (2013) have studied the response of
4 Ecophysicological Aspects 25

Glycyrrhiza inflata to NaCl stress and observed that the higher concentration of
NaCl (˃200 mmol L−1) inhibited growth and development of this taxon.
Selvaraj and Sumithra (2011) have investigated the effect of Glomus aggregatum
(AMF) and PGPR on the growth, nutrient uptake, and biomass of G. glabra. They
report that microbial consortium enhances nutrient uptake and plant biomass
compared to untreated control plants. As salt- and drought-tolerant plant distributed
widely on salt-affected lands liquorice has several advantages under such conditions
(Egamberdieva and Mamedov 2015). Those advantages are
(a) good tolerance to drought and salinity,
(b) its deep root system enables it to reach deep water table following high ion
accumulation,
(c) soil fertility is improved through microbial biomass stimulation as well as
organic matter,
(d) land changes back into high-productive farmland,
(e) generates income for farmers via high-quality forage production for livestock
feeding,
(f) roots are used to produce soft drinks with good medicinal value.
Dirican (2016) has analyzed natural populations of G. glabra from Gaziantep
(Oğuzeli-Yeşildere), Şanlıurfa (Birecik), and Diyarbakır (Karacadağ) provinces
during 2011–2012. He has investigated a wide spectrum of elements like potas-
sium, sodium, calcium, magnesium, zinc, phosphorus, iron, copper, manganese,
lead, cadmium, chromium, nickel, cobalt, molybdenum, selenium, barium, and
vanadium. His data shows highest levels of Na (50,107.58 ± 22,030.09 ppm) and
lowest levels have been recorded for Cd (0.04 ± 0.01 ppm). Co, Mo, and Se were
not detected in the collected samples. His findings stress that overall levels in the
samples collected from Şanlıurfa and Diyarbakır are higher as compared to those
from Gaziantep.
Zhang and Xiong (2008) report that low-energy (25 keV) N+ ions were
implanted into liquorice (G. uralensis) seeds at a fluency of either zero (control) or
900  (2.6  1013) ions/cm2. After irradiation, all the seeds were planted in the
plastic pots for a growth period of 1 month. Thereafter, the seedlings in the pot were
subjected to saline stress at 600 mM for about 3 days. The morphological and
physiological characteristics such as total chlorophyll content, proline level,
activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT),
ATPase, and triphenyl tetrazolium chloride (TTC) reduction in seedling roots were
investigated. Their results indicate that ion irradiation significantly increases the
shoot height, leaflet number, taproot length, lateral root number, and shoot and root
weights of liquorice seedlings with or without saline stress. Furthermore, the total
chlorophyll content, proline level, SOD, POD, CAT, ATPase activities, and root
TTC reduction vigor of seedlings are all found to be significantly increased under
saline stress by ion irradiation compared with their corresponding controls. These
results indicate that ion irradiation can strengthen the resistance of liquorice
26 4 Ecophysicological Aspects

seedlings to saline stress and may have a potential application for the improvement
of plants in sand areas (Zhang and Xiong 2008).
Zhang et al. (2017) have investigated the effect and mechanism of exogenous
silicon (Si) on salt and drought tolerance of G. uralensis seedling by focusing on
the pathways of antioxidant defense and osmotic adjustment. Seedling growth, lipid
peroxidation, antioxidant metabolism, osmolytes concentration, and Si content of
G. uralensis seedlings have been analyzed under control, salt, and drought stress
[100 mM NaCl with 0, 10 and 20% of PEG-6000 (Polyethylene glycol-6000)] with
or without 1 mM Si. An addition of Si markedly affects the growth of G. uralensis
in a combined dose of NaCl- and PEG-dependent manner. Si addition improves
germination rate, germination index, seedling vitality index, and biomass under
control and NaCl conditions. It also increases radicle length under control, NaCl
and NaCl-10% PEG, and decreases radicle length, seedling vitality index, and
germination parameters under NaCl-20% PEG. The salt and drought stress
induced-oxidative stress is modulated by silicon (Si) application. Generally, Si
application increases catalase (CAT) activity under control and NaCl-10% PEG,
ascorbate peroxidase (APX) activity under all treatments, and glutathione
(GSH) content under salt combined drought stress as compared with non-Si
treatments, which resists to the increase of superoxide radicals and hydrogen per-
oxide caused by salt and drought stress and further decreased membrane perme-
ability and malondialdehyde (MDA) concentration. Si application also increases
proline concentration under NaCl and NaCl-20% PEG, but decreases it under
NaCl-10% PEG, indicating that proline plays an important role in G. uralensis
seedling response to osmotic stress. Their study reports that Si could ameliorate
adverse effects of salt and drought stress on G. uralensis likely by reducing
oxidative stress and osmotic stress, and the oxidative stress is regulated through
enhancing of antioxidants (mainly CAT, APX, and GSH) and osmotic stress is
regulated by proline (Zhang et al. 2017).
Afreen et al. (2006) have carried out detailed studies on G. uralensis plants.
They are reporting the occurrence of melatonin in its roots. These workers have
investigated the response of G. uralensis to the red, blue, and white light as well as
UV-B radiation (280–315 nm) for the synthesis of melatonin. Latter was extracted
and quantified by them in seed, root, leaf, and stem tissues. The report shows that
root tissues contain highest concentration of melatonin, which increases with the
development of plant (Afreen et al. 2006). According to their findings after
3 months of growth under red, blue, and white fluorescent lamps, the melatonin
concentrations were the highest in red light exposed plants. The values varied
depending on the wavelength of light spectrum as follows: red, blue, and white.
However, in older plants (6 months of age), melatonin concentration has shown a
considerable increase in 6-month-old red, blue, and white light exposed plants. The
differences between blue and white light exposed plants are not significant. In the
case of root tissues, concentration of melatonin was highest in the plants exposed to
high-intensity UV-B radiation for 3 days followed by low-intensity UV-B radiation
for 15 days. The reduction of melatonin under longer periods of UV-B exposure
points to the fact that melatonin synthesis may be related to the integrated value of
4 Ecophysicological Aspects 27

UV-B irradiation. Melatonin in G. uralensis plant is presumably for protection

against oxidative damage caused as a response to UV irradiation (Afreen et al.
2006). This system has a prospect for evaluation in other living organisms living at
higher altitudes.
G. uralensis has an ability to fix atmospheric nitrogen in the symbiosis through
symbiotic association with Mezorhizobium, a highly specific rhizobia (Wei et al.
2008; Li et al. 2012). They have studied the diversity of Mezorhizobium associated
with G. uralensis and selected salt-tolerant strain Mezorhizobium sp. CCNWGX035.
The strain has been able to grow in the presence of 60 mg mL−1 NaCl (6% NaCl).
Hou et al. (2010) have studied the effects of low light intensity on growth and
accumulation of secondary metabolites in G. uralensis. Hydroponic-cultivated
1-year-old rhizome seedlings were grown under three low irradiances, 200, 100,
and 50 µmol m−2 s−1 for 135 days. Control plants have been cultured under natural
light conditions. Low light intensity stress has decreased leaf thickness, photo-
synthesis, and biomass, but increased leaf area and chlorophyll concentration. Low
light intensity has also significantly increased accumulation of glycyrrhizic acid and
liquiritin in the root, while the maximum values of both secondary metabolites were
obtained under an irradiance of 100 µmol m−2 s−1. Concentrations of both sec-
ondary metabolites were negatively correlated with root biomass (Hou et al. 2010).
The results of these authors suggest that G. uralensis could endure an environment
with low light intensity and suitable light control might increase the secondary
metabolite contents within agroforestry systems.
Li et al. (2011) have reported that 2-year-old seedlings of liquorice plant (G.
uralensis) were exposed to three degrees of water deficit, namely weak (60–70%),
moderate (40–50%), and strong (20–30%) relative water content in soil. The
controls were grown in soil with 80–90% water content. Moderate and strong water
deficit has decreased the net photosynthetic rate, stomatal conductance, and bio-
mass production. Water use efficiency and the root-to-shoot ratio have increased
significantly in response to water deficit, indicating a high tolerance to drought.
Weak water deficit has not decreased root biomass production, but significantly
increased the production of glycyrrhizic acid (by 89%) and liquiritin (by 125%) in
the roots. Therefore, a weak water deficit can increase the yield of root medical
compounds without negative effect on root growth (Li et al. 2011).
Liao and Wang (2014) have published data on the leaf gas exchange and
chlorophyll fluorescence of G. uralensis at two water supplies (equivalent to
240 mm for present precipitation and to 120 mm for future decreasing precipita-
tion). They report a midday depression in net photosynthetic rate (PN) for either
treatments, but stomatal limitation was dominant for present precipitation treatment
and nonstomatal limitation for the drought treatment. Compared with present pre-
cipitation treatment, PN, stomatal conductance (gs), and transpiration rate (E) were
always lower at drought stress, but stomatal limitation value (Ls) and water use
efficiency (WUE) have been higher in the morning. The decrease in carboxylation
efficiency (CE), apparent quantum yield (AQY), light saturated photosynthetic rate,
and maximal photochemical efficiency of photosystem 2 (PS 2) (Fv/Fm) suggest
that rubisco activity is reduced and PS 2 is partially inactivated during the day under
28 4 Ecophysicological Aspects

drought. However, part of this inactivation of PS 2 might be alleviated due to

increased thermal dissipation under drought (Liao and Wang 2014).
Huang et al. (2016) have investigated the increase of watering and N addition
and their effects on the relative growth rate of G. uralensis. Their findings reveal
that the values have increased greatly and then decreased gradually at high amounts
of both of these resources, resulting in an increase in aboveground biomass in most
cases. Within the growth period, the relative growth rate from June to August, with
mean values of 2.40 g g−1 m−2 month−1 in the watering experiment and 2.19 g
g−1 m−2 month−1 in N addition experiment, has been higher than that from June to
October. Along the watering gradient, NRE in the leaves of G. uralensis has
increased from 30.70 to 52.44%, while N concentration in senescing leaves has
declined from 26.68 to 17.58 mg g−1, indicating the increased trend in N resorp-
tion. Along the N addition gradient, NRE has decreased from 45.96 to 34.49% and
the N concentration in senescing leaves has increased from 17.58 to 27.86 mg g−1,
reflecting the opposite trend in N resorption. On average, NRE and the N con-
centration in senescing leaves were 41.66% and 21.69 mg g−1 in the watering
experiment, while 37.08% and 22.45 mg g−1 in the N addition experiment. These
authors have also studied NRP (represented by the N concentration in senesced
leaves) and NRE of G. uralensis. In the non-N addition treatment, the values were
17.6 mg g−1 and 46.0%, showing less dependence on the process of resorption than
other plants. The low N resorption in G. uralensis suggests that senesced-leaf fall
would return high-quality litter to the soil, and thereby would indirectly improve
soil N availability. Because of their contrary effects on soil N availability, N
addition and watering changed N resorption of G. uralensis in opposite ways.
Huang et al. (2016) have also found both decreased NRP and NRE with N addition,
indicating that N fertilization decreases the dependence of this species on acquiring
N from leaf N resorption.
This negative response of N resorption to soil N was in accordance with other
results from natural communities (Wright and Westoby 2003). In contrast, varied
results have been reported related to how N resorption responds to increasing water
availability, including increasing (Drenovsky et al. 2012; Khasanova et al. 2013),
decreasing (Yuan and Chen 2009a, b), or no response (Drenovsky et al. 2010).
Huang et al. (2016) have also observed poorer resorption in plants experiencing
drought, indicating a lower N mobilization that occurs from leaves to plant before
abscission in drought plots. Meanwhile, the decrease of soil N availability caused
by greater amounts of watering makes G. uralensis more dependent on the
resorption approach. Therefore, N addition and watering may affect plant N use
strategy through their influence on N mobility and N release from organic matter in
soils. They also found both N addition and watering increased the relative growth
rate of G. uralensis, with the highest values appearing at medium soil N content and
N:P ratios, especially in the watering experiment. This result proves that the balance
between soil N and P is very important to various plant processes, such as biomass
accumulation (Huang et al. 2016). These authors also report that both NRE and
NRP are negatively related to soil N content and the soil N:P ratio, whereas an
insignificant relationship with the soil C:N ratio is observed in the N addition
4 Ecophysicological Aspects 29

experiment. In contrast, watering has been reported to produce more significant

effects on soil N content, resulting in wider soil C:N:P ratio. Consequently, similar
negative relationships between N resorption with soil N and the N:P ratio are found.
These findings suggest that N addition alleviates N limitation of plant growth,
further reducing plant N dependence on leaf resorption. On the contrary, watering
induces N loss in soil leading to N limitation. Therefore, plants increase their ability
to resorb N from senescent leaves, showing an effective N economy (Huang et al.
2016). Based on these finding of N resorption responding to soil changes in the C:
N:P ratio, together with the response in relative growth rate, these authors conclude
that soil C:N:P ratio also could indicate N limitation for plants growing in the desert
steppe of Northwestern China (Huang et al. 2016).
Grankina et al. (2009) have investigated the trace element composition of the
subsurface (roots and rhizomes), overground (leaves and stems), and reproductive
(bean valves) parts of G. uralensis using synchrotron radiation X-ray fluorescence
analysis (SRXFA). They have measured the concentrations of Ti, Cr, Mn, Fe, Co,
Ni, Cu, Zn, As, Se, Br, Rb, Sr, Y, Zr, Nb, Mo, Hg, Pb, Bi, Th, and U. Their findings
reveal that G. uralensis is an accumulator of Fe, Mn, Cu, and Co.

References

Abd El-Rahman AA, Batanouny KH, Zayed KM (1974). Water relations of Glycyrrhiza glabra L.
under desert conditions. Flora Bd 163(8):143–155
Abe J, Araki H, An P, Shimizu H, Li J, Guo Y, Inanaga S (2005) Combating desertification and
rehabilitating degraded arid lands in Alashan, Inner Mongolia China. Root Res 14(2):51–58 (in
Japanese)
Afreen F, Zobayed SMA, Kozai T (2006) Melatonin in Glycyrrhiza uralensis: response of plant
roots to spectral quality of light and UV-B radiation. J Pineal Res 41(2):108–115
Badalov MA (1996) Multiplication of liquorice naked and its cultivation. Fan Publisher, Tashkent
Dirican S (2016) Diyarbakır yöresinde doğal olarak yetişen meyan kökü (Glycyrrhiza glabra)
bitkisinde bazı eser elementlerin spektroskopik yöntemlerle tayini [Determinatıon of trace
elements in licorice (Glycyrrhiza glabra) naturally growing in Dıyarbakır region with
spectroscopic methods]. Fırat Üniversitesi Fen Bilimleri Enstitüsü, Yüksek Lisans Tezi, Elazığ-
Türkiye
Drenovsky RE, James JJ, Richards JH (2010) Variation in nutrient resorption by desert shrubs.
J Arid Environ 74:1564–1568
Drenovsky RE, Khasanova A, James JJ (2012) Trait convergence and plasticity among native and
invasive species in resource-poor environments. Am J Bot 99:629–639
Egamberdieva D, Mamedov NA (2015) Potential use of licorice in phytoremediation of salt
affected soils. In: Ozturk M et al (eds) Plants. Pollutants and remediation, Springer
Science + Business Media Dordrecht, pp 309–318
Grankina VP, Savchenko TI, Chankina OV, Kovalskaya GA, Kutzenogii KP (2009) Trace element
composition of ural licorice Glycyrrhiza uralensis Fisch. (Fabaceae Family). Contemp Probl
Ecol 2(4):396–399
Hou J-L, Li W-D, Zheng Q-Y, Wang W-Q, Xiao B, Xing D (2010) Effect of low light intensity on
growth and accumulation of secondary metabolites in roots of Glycyrrhiza uralensis Fisch.
Biochem Syst Ecol 38:160–168
30 4 Ecophysicological Aspects

Huang J, Yu H, Zhang F, Li M, Lin H (2016) Water- and N-induced changes in soil C:N: P
stoichiometry and its implications for N limitation of a desert steppe species Glycyrrhiza
uralensis. Pol J Ecol 64(2):241–254
Kerbabaev BB (1971) Protection of liquorice naked production resources. In: Proceeding book of
conference on protection of flora Central Asian Republics and Kazakhstan, Fan Publisher,
Tashkent, pp 252–256
Khasanova A, James JJ, Drenovsky RE (2013) Impacts of drought on plant water relations and
nitrogen nutrition in dryland perennial grasses. Plant Soil 372:541–552
Kushiev H, Noble AD, Abdullaev I, Toshbekov V (2005) Remediation of abandoned saline soils
using Glycyrrhiza glabra: a study for the Hungry Steppes of Central Asia. Int J Agric Sustan
3:102–113
Li WD, Hou JL, Wang WQ, Tang XM, Liu CL, Xing D (2011) Effect of water deficit on biomass
production and accumulation of secondary metabolites in roots of Glycyrrhiza uralensis.
Russ J Plant Physiol 58(3):538–542
Li L, Sinkko H, Montonen L, Wei G, Lindström K, Räsänen LA (2012) Biogeography of
symbiotic and other endophytic bacteria isolated from medicinal Glycyrrhiza species in China.
FEMS Microbiol Ecol 79(1):46–68
Liaoa JX, Wang GX (2014) Effects of drought stress on leaf gas exchange and chlorophyll
fluorescence of Glycyrrhiza uralensis. Russ J Ecol 45(6):532–538
Lu JH, Lu X, Liang YC, Lin HL (2013) Salt tolerance of Glycyrrhiza inflata seedling, in Xinjiang
and its ion response to salt stress. Chin J Plant Ecol 37(9):839–850
Selvaraj T, Sumithra P (2011) Effect of Glomus aggregatum and plant growth promoting rhizo
microorganisms on growth, nutrition and content of secondary metabolites in Glycyrrhiza
glabra L. Indian J Appl Pure Biol 26(2):283–290
Siyamoğlu B (1984) Türkiye’de yetişen meyan köklerinin bileşimi üzerinde araştırmalar. E.U.Z.F.
Dergisi 21(3):61–73
Srivastava M, Purshottam DK, Srivastava AK, Misra P (2013) In vitro conservation of Glycyrrhiza
glabra by slow growth culture. Int J Bio-Technol Res 3(1):49–58
Wei GH, Yang XY, Zhang ZX, Yang YZ, Lindsröm K (2008) Strain Mesorhizobium
sp. CCNWGX035: a stress-tolerant isolate from Glycyrrhiza glabra displaying a wide host
range of nodulation. Pedosphere 18(1):102–112
Wright IJ, Westoby M (2003) Nutrient concentration, resorption and lifespan: leaf traits of
Australian sclerophyll species. Funct Ecol 17:10–19
Yuan ZY, Chen HYH (2009a) Global-scale patterns of nutrient resorption associated with latitude,
temperature and precipitation. Global Ecol Biogeogr 18:11–18
Yuan ZY, Chen HYH (2009b) Global trends in senesced-leaf nitrogen and phosphorus. Global
Ecol Biogeogr 18:532–542
Zhang X, Xiong T (2008) Improving Glycyrrhiza uralensis salt tolerance with N + ion irradiation.
Russ J Plant Physiol 55(3):344–349
Zhang W, Xie Z, Wang L, Li M, Lang D, Zhang X (2017) Silicon alleviates salt and drought stress
of Glycyrrhiza uralensis seedling by altering antioxidant metabolism and osmotic adjustment.
J Plant Res 130:611–624
Chapter 5
Liquorice–Mycorrhiza Interactions

5.1 Glycyrrhiza glabra

In China, liquorice is regarded as a superior balancing or harmonizing agent. It finds

its way in several herbal supplements, it is used as an important food additive and in
making candy as well as other confectionary stuff. The widespread use of this
botanical supplement has thus lead to the large-scale farming of this
crop. Therefore, strategies to increase the supply of liquorice by increasing either
cultivation or plant biomass are highly desirable.
An association of AMF with roots of different plants has been reported to
increase the plant biomass and productivity as well (Duponnois et al. 2001;
Akiyama and Hayashi 2002; Liu et al. 2014). Bao and Yan (2004) have reported
that if naturally growing Glycyrrhiza glabra is infected with AM fungi, it shows a
30% colonization rate in the middle and western regions of Inner Mongolia, China.
Liu et al. (2014) have studied the degree of liquorice root colonization with various
species of AM fungi (alone or in combination) with a result up to about 60%. Their
results have also shown that the highest degree of mycorrhizal root colonization
(myc) could be achieved with Glomus intraradices as compared to the other AM
fungi in all the clones tested. It has been speculated that AM fungi initiate a
signaling cascade resulting in the colonization, and these events do not elicit any
adverse defense reaction from the host (Gadkar et al. 2001). As such, probably AM
symbiosis is a complex genetic mechanism which needs to be investigated at length
to elucidate the possible factors involved in differential colonization of various plant
roots by different species of AMF (Liu et al. 2014).
According to Yadav et al. (2013), the survival rate and development of micro-
propagated plantlets of G. glabra show improvement by introducing effective
mycorrhizal symbiosis. The survival rate of G. glabra plants significantly improves
when inoculated with different treatments of AMF at the beginning of the
acclimatization stage. Inoculation with Glomus mosseae contributes up to 100% of
plantlet survival as opposed to 66.6% of survival in control (Yadav et al. 2013).
It is obvious that the integration of AMF is found to have a significant effect on
the growth and development of micropropagated G. glabra plantlets. However, this
improvement is considerably different with regard to the type of fungal strain used.
It has been found that mycorrhizal inoculation increases the height of the plant in

© The Author(s) 2017 31

M. Öztürk et al., Liquorice, SpringerBriefs in Plant Science,
https://doi.org/10.1007/978-3-319-74240-3_5
32 5 Liquorice–Mycorrhiza Interactions

comparison to the control. The most effective results have been obtained in the dual
combination of Acaulospora laevis + G. mosseae after 120 days of inoculation.
Similar trend has been observed in the case number of leaves per plant. Significant
increment in root length has been observed with G. mosseae followed by dual
combination of G. mosseae + A. laevis. The maximum leaf area has been recorded
with the A. laevis treatment followed by dual combination of G. mosseae + A.
laevis (Yadav et al. 2013). A significant increment in leaf area is observed in the
inoculated plant, which may be due to increased phosphorus uptake resulting in an
enhancement of biosynthesis processes, determining a faster growth and develop-
ment, which leads to a greater leaf area (Yadav et al. 2013).
Biomass of all the inoculated plants of G. glabra increases significantly in
terms of fresh and dry weight of shoots after 120 days of inoculation. A significant
increment in shoot biomass is recorded in dual combination of G. mosseae + A.
laevis followed by G. mosseae (Yadav et al. 2013). AMF plays a dominant role in
increasing phosphorus solubilization and uptake of ions like P, N, Ca, S, K, Mg,
Mn, and Cl by plants (Vestberg and Estaun 1994; Yadav et al. 2013). The reason
may be that AMF hyphae growing through soil pore spaces affect phosphate
absorption beyond the depleted zone. The fungal hyphae transport phosphate over
large distance into the root cortical cells (Parkash and Aggarwal 2009; Kaushih
et al. 2011a; Yadav et al. 2013). They also produce growth-promoting substances
such as indole acetic acid, cytokinins-, and gibberellin-like substances (Karthikeyan
et al. 2008; Kaushih et al. 2011b; Parkash et al. 2011a, b; Yadav et al. 2013).
The results reported by Yadav et al. (2013) clearly indicated the significant
variations among different biochemical parameters treated with different AM fun-
gus. The leaf chlorophyll content recorded in the mycorrhizal plants is typically
higher than non-treated control. Micropropagated plantlets inoculated with G.
mosseae yield the highest amount of total chlorophyll (Yadav et al. 2013).
Similarly, increased chlorophyll “a” and chlorophyll “b” in plants are similar to the
findings of Bavaresco and Fogher (1996) related to the effect of G. mosseae.
Mycorrhizal-treated plants show a greater increase in the rate of photosynthesis than
their controls which may be due to increase in total chlorophyll content (Manoharan
et al. 2008). This increase after AMF inoculation may be due to the higher con-
centrations of ions like Mg, Fe, and Cu in foliar tissues thus influencing chlorophyll
synthesis (Mathur and Vyas 1995; Singh et al. 2012). As compared to other bio-
chemical traits, reducing and total sugar contents decrease in different AMF inoc-
ulated specimens (Yadav et al. 2013). The reason could be that AMF always serves
as a strong sink for sugars and uses 10–20% of net photosynthate in exchange for
the transfer of nutrients to the host to lead a symbiotic life (Allen 1991;
Muthukumar and Udaiyan 2000). Leaf protein shows minor increase in G. mosseae
inoculated plants followed by G. mosseae + A. laevis (Yadav et al. 2013), as
reported by Vazquez et al. (2000) too, who found that total soluble protein content
was significantly higher in mycorrhizal than non-mycorrhizal plants.
Liu et al. (2014) have also investigated the phosphorus concentration in the
leaves and roots of inoculated plants, which is significantly higher in all of the
5.1 Glycyrrhiza glabra 33

inoculated plants than control. Symbivit and G. mosseae treatments have resulted in
significantly higher P accumulation as compared to G. intraradices although the
rate of colonization is better with G. intraradices. Phosphorus concentration is
significantly higher in the inoculated plants than in the phosphorus fertilizer
treatments. The addition of P fertilizer is ineffective mainly because of the low
solubility of phosphates of iron, aluminum, and calcium leading to lower soil
concentrations and mobility. Perhaps, different species of AMF affect the solubility
of phosphates differently, resulting in variations in P concentration. The replace-
ment of P in the “depletion zone” does not keep pace with uptake (Liu et al. 2014).
Leguminous plants have the capability to simultaneously associate with AM fungi
as well as Rhizobium sp. and form both arbuscular mycorrhizae and root nodules.
This tripartite symbiosis involving AM fungi, rhizobia, and leguminous plants
possibly results in better nutrient absorption from the soil (Gage 2004). The
molecular and genetic mechanism regarding this harmonious association is yet to be
elucidated (Liu et al. 2014).
Liu et al. (2014) have also carried out studies on the association with AM fungi.
They report an increase in the dry weight of roots and shoots of liquorice, and this
increase is higher than that observed with direct phosphorus treatment of plants.
Although this effect is more evident in C3 liquorice, the root and shoot biomass
yield in C6 liquorice also increases. The increase in C6, however, is not statistically
significant as compared to the control and P treatments. These are attributed to
genotypic variations between the clones, which in turn may affect the symbiotic
capability of the plant. These workers also corroborate the results by showing that
AM fungi affect the levels of secondary plant compounds. The effects of AM fungi
colonization change with different genotypes. The AM fungi can be applied to
enhance the secondary metabolite content and further the yield of roots and aerial
harvest products in medicinal plants (Liu et al. 2014).
Akhzari (2015) has studied the maximum values of leaf area in 100% FC and
80% FC with AM inoculation treatment (0.78 and 0.67 respectively) in G. glabra.
The leaf area has increased significantly under well-watered and low water-stressed
conditions when compared to the corresponding non-AM seedlings. Moreover, his
study has shown that inoculation in G. glabra could increase plant shoot height and
shoot weight compared to control (Akhzari 2015). The positive effect is likely to be
attributed to the improvement in uptake of water by hyphae (Faber et al. 1991).
The maximum essential oil content of G. glabra has been seen at the 80% FC
with AM inoculation treatment (Akhzari 2015). However, essential oil content in
80% FC with AM inoculation treatment is more than 100% FC with AM inocu-
lation treatment in this species (Akhzari 2015). Generally, under water stress
condition, mycorrhizal fungus stimulates greater essential oil content of treated
plants than those of the non-mycorrhizal plants (Akhzari 2015). Minimum essential
oil content of G. glabra is reported at 20% FC without inoculation treatment
(Akhzari 2015).
Under water stress, mycorrhizal inoculation G. glabra produces further total
protein content than those of non-mycorrhizal plants. Increase in aridity level from
100% FC to 20% FC results in a significant progressive decline in total plant
34 5 Liquorice–Mycorrhiza Interactions

protein content. The report published by Akhzari (2015) shows that increasing
aridity level causes a decline in total plant protein content. However, in some plants,
some proteins (e.g., dehydrins) are synthesized in response to drought stress (Close
and Chandler 1990). Dehydrin family of proteins gets accumulated in a wide range
of plant species under dehydration stress (Close 1996).

5.2 Glycyrrhiza uralensis

This species is one of the main sources of liquorice in China. The consumption
currently is around 10 million tons per year on global basis worldwide. Almost
90% of this originates from China (Fu 2004; Liu et al. 2007). In addition to its
pharmaceutical uses, this natures gift for semiarid ecosystems is a drought-tolerant,
deep-rooted, very important for wind breaking, sand fixing, and soil formation
(Zhang et al. 2000). Overharvesting may lead to serious grassland desertification.
However, increasing demands for liquorice across the global market are leading
toward an exhaustion of the supplies of wild populations and acceleration of
desertification processes in China (Liu et al. 2007). To compensate for its scarcity
and prevent erosion together with desertification of arid as well as semiarid land-
scapes, liquorice cultivation has grown up in China from 1980 onwards. Great
progresses have been made however, still many unsolved problems in its cultivation
in arid areas exist, and some of these being poor quality produce and have low
productivity. The survival and growth of plants in arid soils are greatly dependent
upon the abiotic factors of the soil as well as the activities of microbial populations
(Visser 1985; Liu et al. 2007).

5.2.1 Arbuscular Mycorrhizal Colonization

Studies carried out by Liu et al. (2007) on the colonization of liquorice roots after
inoculation with either a single AM fungus or both fungi have revealed that fre-
quency (F %), intensity (M %), and intensity (m %) values lie around 82.6 ± 5.2%,
60.0 ± 3.6% and 71.9 ± 2.1% for G. mosseae, 80.0 ± 4.7%, 50.0 ± 3.9% and
66.8 ± 3.1% for Glomus versiforme, and 84.6 ± 6.8%, 49.4 ± 2.3% and
58.4 ± 2.3% for both G. mosseae and G. versiforme. No differences have been
observed in the root colonization among the treatments of different inoculation
methods. They further state that in microscopic observations, typical Arum-type
mycorrhizae, arbuscules, vesicles, or hyphae have been observed but Paris-type
mycorrhizae were lacking with the inoculation of G. mosseae or G. versiforme.
These researchers have concluded that colonization frequency of the colonized root
fragments against the total number of root fragments examined is represented by
5.2 Glycyrrhiza uralensis 35

F %, whereas colonization intensity relative to the whole root system is represented

by M % and colonization intensity; as an estimate of the amount of root cortex that
became mycorrhizal. It is represented by m %, relative only to the mycorrhizal root
fraction.

5.2.2 Effects on the Liquorice Development with or Without

AM Fungal Inoculation

A measurement of growth parameters in liquorice after 4 or 30 months undertaken

by Liu et al. (2007) has revealed that AM fungal inoculation significantly increased
shoot development. The inoculation with G. mosseae has been more effective than
G. versiforme after 4 months, however no differences have been recorded between
the species after 30 months. No promotion in the root development of liquorice has
been seen after the 4 months growth following AM fungal inoculation. The root
development has significantly increased at later stage. AM fungal inoculation of G.
mosseae after cultivation up to 30 months has increased the fresh and dry weight of
the root as 68.3 ± 19.4 and 33.8 ± 8.6 g/plant, significantly higher than controls
(12.6 ± 4.7 and 8.7 ± 0.7 g/plant). The effects of the co-inoculation of G. mosseae
and G. versiforme have not proved effective in any improvement in liquorice root
growth as compared to inoculation with either AM fungus (Liu et al. 2007).

5.2.3 Effects on Root Oxidase Activity and Phosphorus

and Potassium Uptake

The a-naphthylamine oxidizing activity has been used as an indicator of root vigor
as well as an index of the peroxidases catalysis in the roots. AM fungal inoculation
has significantly reduced root oxidase activity. The a-naphthylamine oxidase
activity in roots inoculated with AM fungi has been reported to lie between 92.8
and 101.2 µg g−1 dry root weight h−1, which is only about 1/3 of the
non-inoculation plants (300.1 µg g−1 dry root weight h−1). As against this, inoc-
ulation with G. mosseae and G. versiforme, alone or in combination, has signifi-
cantly increased leaf P concentration compared to the controls following their
determination after 4 and 30 months growth. The values for P concentration fol-
lowing G. mosseae inoculation in 4- and 30-month-old liquorice have been reported
to lie between 0.329 ± 0.031% and 0.209 ± 0.002%. These values are signifi-
cantly higher than their controls (0.079 ± 0.020% and 0.175 ± 0.001%).
Accumulation of K has exhibited a slight increase by inoculation of AM fungi
following 30 months posttreatment when compared with the controls, but no uptake
differences have been recorded in the plants after 4 months cultivation (Liu et al.
2007).
36 5 Liquorice–Mycorrhiza Interactions

5.2.4 Glycyrrhizin Production

The studies carried out by Liu et al. (2007) stress the fact that glycyrrhizin is the
major active component, which has great importance from the pharmic and com-
mercial value. The glycyrrhizin production in liquorice has significantly increased
following all inoculation treatments when tested after 4 or 30 months. In the case of
4-month-old liquorice seedling grown in sand with AM fungi inoculation gly-
cyrrhizin content has been recorded to be about 1.26 ± 0.11 mg g−1 dry root
weight for G. mosseae, 0.84 ± 0.01 mg g−1 dry root weight for G. versiforme, and
0.91 ± 0.01 mg g−1 dry root weight for combined treatments. These values are
nearly 0.38–1.07-fold higher than control (0.61 ± 0.02 mg g−1). An increase in the
glycyrrhizin production is more significant after 30 months of cultivation.
Glycyrrhizin content of inoculated plants (13.10 ± 1.58–13.60 ± 1.40 mg g−1) is
reported to be nearly 1.34–1.43-fold higher than untreated controls
(5.60 ± 1.29 mg g−1) (Liu et al. 2007). No differences have been observed among
different inoculation treatments after 30 months of growth. Lower glycyrrhizin
content in the experiments carried out by Liu et al. (2007) is attributed to the poor
growth conditions in sandy soil and short growth period. The values reported by
Teng et al. (2003) for G. uralensis collected from Chinese herb shops in China lie
around 17.05–33.21 mg g−1.
G. mosseae and G. versiforme have been used in the inoculation program by Liu
et al. (2007) to study the effect of AM fungi on liquorice growth in sand. Their
results indicate that AM fungi, inoculated either alone or in combination, suc-
cessfully colonized liquorice roots, resulting in taller and healthy plants as com-
pared to the non-inoculation ones. The application of AM fungi has proved
beneficial in the cultivation of this plant on degraded arid lands (Liu et al. 2007).
They tested the plant responses to the combination of the two AM species, and
found no synergistic effect, which is ascribed to the failure of increasing the col-
onization ratio by dual inoculation. Only Arum-type morphology has been observed
with tested AM fungi colonizing liquorice, which more commonly occurs in crop
plants whereas, plants usually inhabiting natural ecosystems show Paris types
(Smith and Smith 1997; Ahulu et al. 2005). Former are usually fast growing, and
grow well under sunlight, whereas latter seem to be shade loving and slow growing
(Brundrett and Kendrick 1990a, b).
Inoculation of two AM fungi, alone or in combination, has no effect on liquorice
root morphogenesis at the early stages of growth, however with the elongation of
cultivation, AM fungal inoculations exhibit great potential to increase the liquorice
root development. This suggests that time is required for the establishment of a
compatible plant–fungus mutualistic relationship (Liu et al. 2007). Similarly, Gange
(2000) has found that AM fungal inoculation, either alone or in combination,
significantly increases the uptake of phosphorus and potassium especially at the
5.2 Glycyrrhiza uralensis 37

early stage of seedlings, which might mainly be ascribed to a greater absorptive

surface inside the plant, due to the effective absorptive area of roots by formation of
an extensive extraradical hypha network which enhances efficiency in the absorp-
tion of nutrients (George 2000; Ravnskov and Jakobsen 1995). All these contribute
toward the output of liquorice shoot height and fresh weight, as well as the resis-
tance to the stressed conditions. According to Liu et al. (2007), most interesting
observation in this connection has been that AM fungal inoculation significantly
reduces the root a-naphthylamine oxidation activity. Latter activity is normally
used as an indicator of root vigor and is also considered as an index of the per-
oxidase catalysis (Zhang 1990). But, peroxidases are among the major enzymes in
chloroplasts to scavenge H2O2 produced through dismutation of O2– by superoxide
dismutase (SOD) (Asada and Takahashi 1987; Ozyigit et al. 2016). The results
published by Liu et al. (2007) related to the AM in 4 months liquorice plants show
values with lower a-naphthylamine oxidase activity which might indicate that AM
fungi inoculation probably decreases peroxidases catalysis. In some studies, pres-
ence of AM fungi has greatly decreased Mn-sodII gene expression relative to
non-mycorrhizal plants under well-watered conditions, resulting in low transcrip-
tional level of SOD (Ruiz-Lozano 2003). As such, naphthylamine oxidation activity
probably is not directly correlated with root vigor of mycorrhizal liquorice
(Liu et al. 2007).
The inoculation of AM fungi has the capability to increase the production of
glycyrrhizin in the roots of liquorice, however the mechanism related to such
increases still are not clear. According to Liu et al. (2007), more detailed investi-
gations are needed for an exploration of biosynthetic pathways and biological
functions of root secondary metabolites. The b-amyrin, lupane-type triterpen, a
possible precursor of glycyrrhizin has been detected in the callus mass of liquorice
(Ayabe et al. 1980). Terpenoids have been reported to play a key role in plant–
microbe interactions (Paiva 2000), but it is not clear as yet whether the glycyrrhizin
in liquorice, as derivatives of terpenoid saponins, has the function to form sym-
biosis with both rhizobia and AM fungi (Liu et al. 2007). The results published by
Liu et al. (2007) have confirmed that mycorrhizal inoculation improves the quality
of liquorice through an increase in the glycyrrhizin production. The production
however was still lower as compared to other reports. Glycyrrhizin content varies
related to the growth stage, the 4th year growth is reported to be the best (Liu et al.
2004). Relatively lower glycyrrhizin content in some studies may be attributed to
the poor growth condition in sandy soils and the short growth period (Liu et al.
2007). We can conclude that data of inoculation of AM fungi provides useful
information for large-scale production of liquorice with better quality in dry arid
zones and deserts. The improved growth, yield, and nutrient uptake in liquorice
demonstrate the potential to restore a selfsustaining vegetation cover and to combat
desertification by introducing AM fungi (Liu et al. 2007).
38 5 Liquorice–Mycorrhiza Interactions

References

Ahulu EM, Nakata M, Nonaka M (2005) Arum- and Paris type arbuscular mycorrhizas in a mixed
pine forest on sand dune soil in Niigata Prefecture, central Honshu, Japan. Mycorrhiza 15
(2):129–136
Akhzari D (2015) Response of Glycyrrhiza glabra L. to arbuscular mycorrhizal fungi and water
stress. J Essent Oil Bearing Plants 18(4):992–1002
Akiyama K, Hayashi H (2002) Arbuscular mycorrhizal fungus-promoted accumulation of two new
triterpenoids in cucumber roots. Biosci Biotechnol Biochem 66(4):762–769
Allen MF (1991) The ecology of mycorrhizae. Cambridge University Press, Cambridge
Asada K, Takahashi M (1987) Production and scavenging of active oxygen in photosynthesis. In:
Kyle DJ et al (eds) Photoinhibition. Elsevier, Amsterdam, pp 227–287
Ayabe S, Kobayashi M, Hikichi M, Matsumoto K (1980) Flavonoids from the cultured cells of
Glycyrrhiza echinata. Phytochemistry 19:2179–2183
Bao YY, Yan W (2004) Arbuscular mycorrhizae and their structural types on common plants in
grasslands of mid-western Inner Mongolia. Biodiversity Sci 12(5):501–508
Bavaresco L, Fogher C (1996) Lime-induced chlorosis of grapevine as affected by rootstock and
root infection with arbuscular mycorrhiza and Pseudomonas fluorescens. Vitis 35:119–123
Brundrett MC, Kendrick WB (1990a) The roots and mycorrhizae of herbaceous woodland plants.
I. Quantitative aspects of morphology. New Phytol 114:457–468
Brundrett MC, Kendrick WB (1990b) The roots and mycorrhizae of herbaceous woodland plants.
II. Structural aspects of morphology. New Phytol 114:469–479
Close TJ (1996) Dehydrins: Emergence of a biochemical role of a family of plant dehydration
proteins. J Plant Physiol 97:795–803
Close TJ, Chandler PM (1990) Cereal dehydrins: serology, gene mapping and potential functional
roles. Aust J Plant Physiol 17:333–344
Duponnois R, Plenchette C, Bâ AM (2001) Growth stimulation of seventeen fallow leguminous
plants inoculated with Glomus aggregatum in Senegal. Eur J Soil Biol 37(3):181–186
Faber BA, Zasoski RJ, Munns DN, Shackel K (1991) A method for measuring hyphal nutrient and
water uptake by mycorrhizal plants. Can J Bot 69:87–94
Fu YJ (2004) Gan Cao: the Chinese licorice. Science Press, Beijing New York
Gadkar V, David-Schwartz R, Kunik T et al (2001) Arbuscular mycorrhizal fungal colonization.
Factors involved in host recognition. Plant Physiol 127(4):1493–1499
Gage DJ (2004) Infection and invasion of roots by symbiotic, nitrogen-fixing rhizobia during
nodulation of temperate legumes. Microbiol Mol Biol Rev 68(2):280–300
Gange AC (2000) Arbuscular mycorrhizal fungi, collembola and plant growth. Trends Ecol Evol
15(9):369–372
George E (2000) Nutrient uptake. In: Kapulnick Y, Douds DD (eds) Arbuscular mycorrhizas:
physiology and function. Kluwer Academic Publishers, Netherlands, pp 288–307
Karthikeyan B, Jaleel CA, Changxing Z, Joe MM, Srimannarayan J, Deiveekasundaram M (2008)
The effect of AM fungi and phosphorus level on the biomass yield and ajmalicine production in
Catharanthus roseus. EurAsian J Biosci 2:26–33
Kaushih S, Kumar A, Aggarwal A (2011a) Influence of hosts and substrates on mass
multiplication of Glomus mosseae. Afr J Agric Res 6:2971–2977
Kaushih S, Kumar A, Aggarwal A, Parkash V (2011b). Influence of inoculation with the
endomycorrhizal fungi and Trichoderma viride on morphological and physiological growth
parameters of Rauwolfia serpentina Benth. ex. Kurtz. Indian J Microbiol https://doi.org/10.
1007/s12088-011-0215-1
Liu JR, Zhao WB, Wang HY, Jiang FSH, Xiang Y, Li XY, Zhu Y (2004) Output of cultivated
glycyrrhizia in different growth stages and analytical comparison of its active ingredients.
Shanghai J Tradit Chin Med 11(38):56–58
References 39

Liu J, Wu L, Wei S, Xiao X, Su C, Jiang P, Song Z, Wang T, Yu Z (2007) Effects of arbuscular

mycorrhizal fungi on the growth, nutrient uptake and glycyrrhizin production of licorice
(Glycyrrhiza uralensis Fisch). Plant Growth Regul 52:29–39
Liu H, Tan Y, Nell M, Zitter-Eglseer K, Wawscrah C et al (2014) Arbuscular mycorrhizal fungal
colonization of Glycyrrhiza glabra roots enhances plant biomass, phosphorus uptake and
concentration of root secondary metabolites. J Arid Land 6(2):186–194
Manoharan PT, Pandi M, Shanmugaiah V, Gomathinayagam S, Balasubramanian N (2008) Effect
of vesicular arbuscular mycorrhizal fungus on the physiological and biochemical changes of
five different tree seedlings grown under nursery conditions. Afr J Biotechnol 7:3431–3436
Mathur N, Vyas A (1995) Influence of VA mycorrhizae on net photosynthesis and transpiration of
Ziziphus mauritiana. J Plant Physiol 147:328–330
Muthukumar T, Udaiyan K (2000) The role of seed reserves in arbuscular mycorrhizal formation
and growth of Leucaena leucocephala (Lam.) de Wit. and Zea mays L. Mycorrhiza 9:323–330
Ozyigit II, Filiz E, Vatansever R, Kurtoglu KY, Koc I, Ozturk M, Anjum N (2016) Identification
and comparative analysis of H2O2-scavenging enzymes (Ascorbate Peroxidase and Glutathione
Peroxidase) in selected plants employing bioinformatics approaches. Front Plant Sci 7(301).
www.frontiersin.org
Paiva NL (2000) An introduction to the biosynthesis of chemicals used in plant microbe
interactions. J Plant Growth Regul 19:131–143
Parkash V, Aggarwal A (2009) Diversity of endomycorrhizal fungi and their synergistic effect on
the growth of Acacia catechu Willd. J For Sci 55:461–468
Parkash V, Aggarwal A, Sharma V (2011a) Rhizospheric effect of vesicular arbuscular
mycorrhizal inoculation on biomass production of Ruta graveolens L.: a potential medicinal
and aromatic herb. J Plant Nutr 34:1386–1396
Parkash V, Sharma S, Aggarwal A (2011b) Symbiotic and synergistic efficacy of endomycorrhizae
with Dendrocalamus strictus L. Plant Soil Environ 57:447–452
Ravnskov S, Jakobsen I (1995) Functional compatibility in arbuscular mycorrhizas measured as
hyphal P transport to the plant. New Phytol 129:611–618
Ruiz-Lozano JM (2003) Arbuscular mycorrhizal symbiosis and alleviation of osmotic stress. New
perspectives for molecular studies. Mycorrhiza 13:309–317
Singh NV, Singh SK, Singh AK, Meshram DT, Suroshe SS, Mishra DC (2012) Arbuscular
mycorrhizal fungi (AMF) induced hardening of micropropagated pomegranate (Punica
granatum L.) plantlets. Sci Hortic 136:122–127
Smith FA, Smith SE (1997) Structural diversity in (vesicular)-arbuscular mycorrhizal symbioses.
New Phytol 137:373–388
Teng SC, Tsai HJ, Tsai MC, Lee WM, Chen LC, Lin CC (2003) Using both chemical and
biological fingerprints for the quality of the study of estrogenic licorice (Glycyrrhiza uralensis).
J Food Sci 68(7):2372–2377
Vazquez M, Cesar S, Azcon R, Barea JM (2000) Interactions between arbuscular mycorrhizal
fungi and other microbial inoculants (Azospirillum, Pseudomonas, Trichoderma) and their
effects on microbial population and enzyme activities in the rhizosphere of maize plants. Appl
Soil Ecol 15:261–272
Vestberg M, Estaun V (1994) Micropropagated plants, an opportunity to positively manage
mycorrhizal activities. In: Gianinazzi S, Schüepp H (eds) Impact of AMF on sustainable
agriculture and natural ecosystems. Birkhauser Verlag, Basel, pp 217–225
Visser S (1985) Management of microbial processes in surface mined land reclamation in western
Canada. In: Tate RL, Klein DA (eds) Soil reclamation processes: microbiological analyses and
applications. Marcel Dekker, New York, Basel, pp 203–241
Yadav K, Aggarwal A, Singh N (2013) Arbuscular mycorrhizal fungi induced acclimatization and
growth enhancement of Glycyrrhiza glabra L.: a potential medicinal plant. Agric Res 2(1):
43–47
40 5 Liquorice–Mycorrhiza Interactions

Zhang ZL (1990) A guide of phytophysiological experiment. Higher Education Press, Beijing,

pp 57–62
Zhang J, Yao J, Ding L (2000) Study advances on the utilization of Glycyrrhiza. Grassland Turf 89
(2):12–17
Chapter 6
Molecular Aspects

6.1 Cytogenetics

The diploid chromosomes complement of Glycyrrhiza glabra is reported to be

2n = 16 (Darlington and Wylie 1955). Some workers have undertaken caryological
analyses to determine morphological and biological polymorphism in different
populations of G. glabra, Glycyrrhiza lepidota and Glycyrrhiza echinata. In spite of
the morphological variations, these species revealed a stable chromosome number
supporting the earlier investigations (Rao 1993). However, total and relative lengths
of chromosome pairs and centromeric indices differ among species. Some resear-
ches in uzbekhistan have recorded normal meiosis in six different Glycyrrhiza
species. (Rao 1993; Ashurmetov 1996).

6.2 Genetic and Biotechnology

Recent advents in molecular biology and biotechnology have lead to the efforts to
improve/increase the yield of compounds in plants which are of economic impor-
tance (Rao 1993). The importance of liquorice in food and pharmaceutical industry
has been extensively investigated scientifically. Its biochemistry and derivatives
have attracted great attention. New compounds have been reported from this plant
after using new and improved analytical methods.
The plant tissue culture techniques have become powerful tools for studying the
basic and applied aspects of plant sciences. These methods have found wide range
of applications from propagation of plants to the use of bioreactors and immobilized
cell technology (Rao 1993). One of these is “micropropagation”. A review by Bajaj
et al. (1988) presents a detailed account of the usefulness of in vitro techniques of
higher plants for medicinal and industrial production of important biochemical
components. In vitro micropropagation techniques were found advantageous to
supersede the problems encountered with propagation by conventional methods.
The benefits associated with this technology are increase in the rate of propagation,
rapid multiplication of plants which in a particular climate do not promote ger-
mination of seeds, availability of plants throughout the year, uniformity of selected
genotypes, production of uniform clones, and conservation of genetic resources

© The Author(s) 2017 41

M. Öztürk et al., Liquorice, SpringerBriefs in Plant Science,
https://doi.org/10.1007/978-3-319-74240-3_6
42 6 Molecular Aspects

(Bajaj et al. 1988). Additionally, this type of multiplication procedure of medicinal

plants avoids the problems connected with the loss of biosynthesis pathways in
dedifferentiated tissues in vitro (Rao 1993). Moreover, different types of clonal
propagation methods are in use for the micropropagation of various crops. The most
routinely used practice is direct propagation from existing meristems, through
which identical plants with desired characters can be obtained (Bajaj 1988). The
micropropagation of Glycyrrhiza has also been attempted by Shah and Dalal
(1982). From biotechnological point of view, exploitation of cells suspension
cultures provides an appropriate system for the production of secondary metabolites
on an economical scale in bioreactors. The metabolic pathways involved in sec-
ondary metabolism are often complex in nature and living cells have become the
only source. It is also the case with liquorice, because the approaches on chemical
synthesis of liquorice derivatives have not been successful. The few familiar pro-
cedures to increase the yield of medicinally important compounds are outlined
below (Rao 1993).
In recent years, the development of techniques has improved tremendously, in
addition to the established methods, new and refined methods for manipulating
DNA in vitro is offering many exciting and novel opportunities. Fundamental
questions regarding the control of plant secondary metabolism can be tackled and
ultimately the ability to influence secondary product accumulation, both qualita-
tively and quantitatively, in plants and in tissues grown in vitro is possible (Rao
1993).
Earlier studies have fully stressed the morphological and genetic variations in the
specimens collected from different regions (Koji et al. 2001; Li et al. 2011).
Divergence of wild populations has been successfully identified using molecular
tools such as DNA markers. Molecular genetic diversity studies on Glycyrrhiza
species have been carried out with random amplified polymorphic DNA (RAPD)
(Khan et al. 2009), inter-simple sequence repeat (ISSR) (Yao et al. 2008), and
amplified fragment length polymorphism (AFLP) (Zhang et al. 2010) markers.
Yamazaki et al. (1994) used RAPD and restriction fragment length polymorphism
(RFLP) analysis to determine genetic relationships among Glycyrrhiza species and
found that G. glabra and Glycyrrhiza uralensis, taxa richer in glycyrrhizin, are
more closely related than G. echinata and Glycyrrhiza pallidiflora. Gao et al.
(2010) have analyzed the molecular characterization of G. glabra, G. uralensis, and
Glycyrrhiza inflata species by ITS2 (Internal transcribed spacer) regions and the
intraspecific variation and interspecific differences in liquorice have been deter-
mined. Altay et al. (2016) have studied ecological characteristics and phylogenetic
relationships among and within three Glycyrrhiza species (G. glabra var. glan-
dulifera, G. flavescens ssp. flavescens and G. echinata) collected from East
Mediterranean Area of Turkey by using 14 Simple Sequence Repeat (SSR) primers.
They report that G. flavescens ssp. flavescens is genetically clearly distinguished
from G. glabra var. glandulifera and G.echinata. Their results suggest that
molecular genetic data was significantly correlated with most of ecological and
6.2 Genetic and Biotechnology 43

geographical data. Erayman et al. (2014) have studied the transferability of SSR
markers from distantly related legumes Medicago truncatula, Phaseolus vulgaris,
and Cicer arietinum to Glycyrrhiza species. The highest transferability rate (33%)
has been obtained from M. truncatula markers, while the highest genetic diversity
values have been obtained in P. vulgaris markers.

References

Altay V, Karahan F, Öztürk M, Hakeem KR, Ilhan E, Erayman M (2016) Molecular and
ecological investigations on the wild populations of Glycyrrhiza L. taxa distributed in the East
Mediterranean Area of Turkey. J Plant Res 129(6):1021–1032
Ashurmetov OA (1996) Pylogeny of genera Glycyrrhiza L. and Meristotropis Fisch. & Mey. In:
Ozturk et al (ed) Proceeding of the IV th Plant Life in Southwest Asia Symposium held in
Izmir, Turkiye 21–28 May, 1995, Ege University Press, Izmir.
Bajaj YPS (1988) Biotechnologcy in agriculture and forestry, medicinal and aromatic plants I, vol
4. Springer-Verlag, New York, USA
Bajaj YPS, Furmanowa M, Olszowska O (1988) Biotechnology of the micropropagation of
medicinal and aromatic plants. In: Bajaj YPS (ed) Biotechnology in agriculture and forestry,
medicinal and aromatic plants I, vol 4. Springer-Verlag, New York, USA, pp 60–103
Darlington CD, Wylie AP (1955) Chromosome atlas of flowering plants. George Allen & Unwin
Ltd, London, p 163
Erayman M, Ilhan E, Güzel Y, Eren AH (2014) Transferability of SSR markers from distantly
related legumes to Glycyrrhiza species. Turk J Agric For 38:32–38
Gao T, Yao H, Song J, Liu C, Zhu Y, Ma X, Pang X, Xu H, Chen S (2010) Identification of
medicinal plants in the family Fabaceae using a potential DNA barcode ITS2.
J Ethnopharmacol 130:116–121
Khan S, Mirja KJ, Tayyab M, Abdin MZ (2009) RAPD profile for authentication of medicinal
plant Glycyrrhiza glabra L. Med Aromat Plant Sci Biotech 3:48–51
Koji K, Kazuo O, Hitoshi W, Makio S, Genjiro K, Katsumi T (2001) Classification of Glycyrrhiza
plants by random amplified polymorphic DNA analysis. Discrimination of Glycyrrhiza glabra
L. and G.uralensis Fischer. Jpn Sci Technol Agency J 55(6):287–293 (Japan)
Li M, Cao H, But PPH, Shaw PC (2011) Identification of herbal medicinal materials using DNA
barcodes. J Syst Evol 49(3):271–283
Rao KVS (1993) A review on Licorice. Ancient Sci Life XIII(1-2):57–88
Shah PR, Dalal KC (1982) Plant Tissue Cult. In: 5th meet, pp 685–686
Yamazaki M, Sato A, Shimomura K, Saito K, Murakoshi I (1994) Genetic relationships among
Glycyrrhiza plants determined by RAPD and RFLP analyses. Biol Pharm Bull 17:1529–1531
Yao H, Zhao Y, Chen DF, Chen JK, Zhao TS (2008) ISSR primer screening and preliminary
evaluation of genetic diversity in wild populations of Glycyrrhiza uralensis. Biol Plant 52:
117–120
Zhang F, Chen S, Chen F, Fang W, Li F (2010) A preliminary genetic linkage map of
chrysanthemum (Chrysanthemum morifolium) cultivars using RAPD, ISSR and AFLP
markers. Sci Horticulturae 125(3):422–428
Chapter 7
Pharmacological Activities
and Phytochemical Constituents

Glycyrrhiza glabra is one of the most popular medicinal plants and it has been used in
traditional herbal remedy since ancient times (Blumenthal et al. 2000; Parvaiz et al.
2014; Altay et al. 2016). Many experimental, pharmacological and clinical studies
show that liquorice has antimicrobial, antibacterial, antiviral, antifungal, antihepa-
totoxic, antioxidant, antiulcer, anti hemorrhoid antihyperglycemic, antidiuretic,
antinephritic, anticarcinogenic, antimutagenic, anticytotoxic, anti-inflammatory, and
blood stopper activity (Zani et al. 1993; Paolini et al. 1999; Nomura et al. 2002; Fukai
et al. 2003; Zamansoltani et al. 2009; Sofia and Walter 2009). The liquorice root
extract has been shown to be beneficial for the eye diseases, throat infections, peptic
ulcers, arthritic conditions, liver diseases, joint diseases, immunodeficiency (Gupta
et al. 2008), cough, cancer, diabetes, tuberculosis, endocrinal diseases, respiratory
diseases (Asl and Hosseinzadeh 2008), kidney diseases (Vivekanand 2010), bron-
chitis, asthma, psoriasis, eczema, hemorrhoids (Sofia and Walter 2009), epilepsy,
chronic hepatitis, heart diseases (Chopra et al. 2013), and orodental diseases (Messier
et al. 2012). Also, studies have shown that the extract helps to regulate the estrogen–
progesterone ratio (Kumagai et al. 1967; Nomura et al. 2002; Simmler et al. 2013)
and gastrointestinal system (Asl and Hosseinzadeh 2008).
Pharmacological studies have confirmed that Glycyrrhiza species exhibit a broad
range of biological activities. Many pharmacological activities such as hyporc-
holesterolemic and hypoglycemic activities (Sitohy et al. 1991), anxiolytic activity
(Ambawade et al. 2001), antimicrobial (Patil et al. 2009), antiviral (Cinatl et al.
2003), preliminary free radical scavenging (Toshio et al. 2003), antiulcer (Da
Nagao et al. 1996), cytotoxic, antitumor (Hossain et al. 2004), antiallergic (Ram
et al. 2006; Kroes et al. 1997), antidiabetic (Isbrucker and Burdock 2006), anti-
carcinogenic (Satomi et al. 2005), antioxidant (Vaya et al. 1998), anti-inflammatory
(Kakegawa et al. 1992; Fujisawa et al. 2000), hepatoprotective activity (Wu et al.
2006), skin eruptions, dermatitis, and eczema (Akhtar et al. 2011) have been
reported for roots of Glycyrrhiza species. The licorice can be also used in the
management of impaired learning, dementia, Alzheimer’s disease, and other neu-
rodegenerative disorders (Chakravarthi et al. 2012).

© The Author(s) 2017 45

M. Öztürk et al., Liquorice, SpringerBriefs in Plant Science,
https://doi.org/10.1007/978-3-319-74240-3_7
46 7 Pharmacological Activities and Phytochemical Constituents

7.1 Phytochemistry of Components

The wide use of G. glabra is due to two main constituents, the saponins and
flavonoids (Nomura and Fukai 1998). Glycyrrhizin is the most sweet-tasting
triterpene saponin in roots and stolons of the liqourice plant. Its sweetness is
measured to be nearly 200 times more than that of sucrose (Blumenthal et al. 2000).
Production of a high-concentration glycyrrhizin within a very short time period has
been clearly demonstrated in controlled environments (Afreen et al. 2005).
However, several active substances in these roots are found which include gly-
cyrrhizin, glycyrrhizinic acid (Tang and Eisenbrand 1992), glabridin, glabrene,
glabrol, licoflavonol, glycyrol, glycyrretol, isoglaborlide, licoricone, formononetin,
phaseollinisoflavan, hispaglabridin A and B, 3-hydroxy glabrol, 3-methoxy glab-
ridin (Kinoshita et al. 2005; Fukai et al. 2003; Williamson 2003), glabranin isomer,
narigenin, lupiwightenone (Biondi et al. 2005; Sultana et al. 2010). All these have
been isolated previously. The yellow color of liquorice is due to the flavonoid
content of the plant, which includes liquiritin, isoliquiritin (a chalcone), and other
compounds (Yamamura et al. 1992; Sharma and Agrawal 2013).
The secondary metabolites are mainly the biologically active compounds toge-
ther with their derivatives such as flavanoids (Kar 2007; Varsha et al. 2013),
phenolics (Cai et al. 2004), saponins (Sarker and Nahar 2007; Vashist and Sharma
2013), alkaloids (Sarker and Nahar 2007; Varsha et al. 2013), terpenes (Martinez
et al. 2008), glycosides (Firn 2010), tannins (Kar 2007; Varsha et al. 2013),
anthraquinones (Maurya et al. 2008; Vashist and Sharma 2013), essential oils
(Martinez et al. 2008; Vashist and Sharma 2013), and steroids (Madziga et al. 2010;
Varsha et al. 2013). The major constituents of this extract are sugars, starch, bitters,
resins, essential oils, tannins, inorganic salts, and low levels of nitrogenous con-
stituents such as proteins, individual amino acids, and nucleic acids (Hoffmann
1990; Isbrucker and Burdock 2006). More than 400 compounds have been isolated
from Glycyrrhiza species and triterpene saponins and flavonoids are the main
constitutes with a wide biological activity (Zhang and Ye 2009). Thus far, at least
80 compounds, including triterpenoid saponins, flavonoid glycosides, and free
phenolics have been isolated from Glycyrrhiza inflata (Yang et al. 2015).
Kajiyama et al. (1992) have reported that 2 new prenylflavones, licoflavones B and
C, and one new dibenzoylmathane, glycyrdione C, have been isolated from the root of
G. inflata together with two known flavones, licoflavone A and 4′,7-dihydroxy-
flavone. Their structures have been elucidated on spectroscopic evidence as 4′,7-dihy-
droxy-3′,6-diprenylflavone, 8-prenyl-4′,5,7-trihydroxyflavone, and 1-(2,2-dimethyl-
7-hydroxy-2H-l-benzopyran-6-yl)-3-(4-hydroxy-3-prenyl-phenyl)1-, 3-propane
dione (Kajiyama et al. 1992). The chemical composition of liquorice has actually
been studied by means of classical targeted analysis, especially in relation to tradi-
tional oriental medicine (Wang et al. 2011). Some recent studies have reported more
extensive chemical characterizations. However, these sometimes are lacking in
method standardization, identification criteria, or biochemical evaluations (Rizzato
et al. 2017).
7.1 Phytochemistry of Components 47

An untargeted metabolomic analysis of 3 liquorice species (G. glabra, G. inflata,

and Glycyrrhiza uralensis) has been performed by Rizzato et al. (2017). Their aim
has been to identify the differences in the metabolic pattern of these plants. Most of
the identified compounds determined belong to the classes of flavonoids and
saponins, which are known to have a large range of biological activity, as shown in
previous studies. However, their metabolomic analysis has elucidated the most
important differences in the composition pattern of metabolites in these 3 species.
By means of chemometrics tools (PCA, HCA), they were able to highlight
numerous molecular markers, some already known, but others previously unre-
ported (Rizzato et al. 2017).
The main differences in the metabolome composition of these species are
reported to be the presence of prenylated chalcones in G. inflata, as well as the
presence of numerous compounds in G. glabra normally found in Moraceae family.
These compounds have never been isolated previously in G. glabra (Rizzato et al.
2017). The work undertaken by the latter authors appears to be very useful to
improve the comprehension of the species-specific chemical characteristics of
liquorice. A group of molecules containing sulfate has also been detected. This has
been proved to be useful to distinguish the Chinese liquroice from the European
species. The work carried out by Rizzato et al. (2017) demonstrates that from the
genetical point of view a notable similarity exists between the two Chinese species,
in terms of metabolite composition. They have reported that generally for all
species, the highlighted differences can be ascribed mainly to the genetic factors.
The role of environmental and geographical factors in the variability of Glycyrrhiza
metabolome remains unclear. The work published by these authors substantially
contributes to the knowledge of liquorice metabolite composition. In spite of this,
further studies are needed for a better characterization of the metabolome of these
plants, in order to achieve a deeper understanding of their value as food and herbal
medicine.
A study published by Dobrea (2016) deals with the determination of flavonoid
characteristics in the roots of the two species (Glycyrrhiza echinata and G. glabra)
in Romania, using a sensitive analysis method the Liquid Chromatography—Mass
Spectrometry (LC/MS). This study has been conducted to see if they have similarity
in composition. Their published data shows that liquorice (G. glabra) extracts
contain saponins and flavonoids and exibit numerous pharmacological activities. In
order to establish the degree of similarity between G. glabra and G. echinata roots,
liquiritin, liquiritigenin, isoliquiritigenin, and glabridin have been quantified by
LC/MS in 1% methanolic total extracts (Dobrea 2016). G. glabra contained all the
analyzed flavonoids, among these, liquiritin and glabridin are present in higher
concentrations. According to their findings, glabridin is absent in G. echinata roots
and the liquiritin, liquiritigenin, and isoliquiritigenin content are by far inferior to
G. glabra. In view of this, G. echinata roots should not replace the medicinal
product liquiritiae radix as they lack glabridin and possess reduced concentrations
of other analyzed flavonoids. So, the phytochemistry of G. glabra roots differs from
G. echinata roots. The two are not equivalent. The roots of latter lack the specific
compounds correlated to the therapeutic activity of licorice (Dobrea 2016).
48 7 Pharmacological Activities and Phytochemical Constituents

7.1.1 Flavanoids

More than 300 flavanoids have been isolated from Glycyrrhiza species and they are
responsible for its yellow color. Especially, G. glabra has yellow color due to the
flavonoids like liquiritin, isoliquiritin (Yamamura et al. 1992). The flavanones and
chalcones are the main types among these (Herz et al. 1998; Li et al. 2000; Zhang
and Ye 2009). A number of flavonoids have been identified in these roots such as
liquiritin, liquiritigenin, rhamnolliuiritin, liquiritin apioside, gralbranin, glabrol,
licoflavanone, isoliquiritigenin, neoisoliquiritin, licuraside, licochalcone A and B,
licoricidin, 7-methillicoricidin, hispaglabridin A and B, liocflavone A and B, lioc-
flavanol, glyzaglabrin, licoisoflavanone, glabroisoflavanone, glabrone, licoricone,
gancaonin (Lou and Qin 1995; Xing et al. 2003; Williamson 2003; Zhang and Ye
2009). 5,8-Dihydroxyflavone-7-O-b-d-glucuronide, glychionide A, and 5-hydroxy-
8-methoxyl-flvone-7-O-b-d-glucuronide, glychionide B have been isolated from the
roots of G. glabra (Li et al. 2005). The glabridin, galbrene, glabrone, shinptero-
carpin, licoisoflavones A and B, formononetin, glyzarin, and kumatakenin iso-
flavonoid derivatives too are present in liquorice (Williamson 2003). Also,
hispaglabridin A and B, 4′O-methylglabridin and 3′-hydroxy-, 4′-O-methylglabridin
(De Simone et al. 2001; Haraguchi 2001), and glabroisoflavanone A and B
(Kinoshita et al. 2005) have been found in the liquorice roots.
The flavonoid glycosides have been isolated with feruloyl or coumaroyl groups
and with indole conjugates (Hatano et al. 1998). Similarly, bioactive flavonoid
compounds, liquiritigenin and isoliquiritigenin, have been isolated and identified
from the crude extract of G. uralensis by Ma et al. (2005). Franceschelli et al.
(2011) have identified the licocalchone C, the structural isomer of licocalchone A.
Other flavonoids like licoagrodin, licoagrochalcones, glyinflanin B, and glycyr-
dione A have also been reported (Asl and Hosseinzadeh 2008, 2012; Christensen
and Kharazmi 2001; Li et al. 2000). The glabridin and hispaglabridin B have been
identified by Gupta et al. (2008) from the ethanolic extract of the roots of G. glabra.
The bioactive compounds glepidotin B and glepidotin A have been isolated and
identified from the extract of Glycyrrhiza lepidota by Manfredi et al. (2001),
whereas isoflavonoid derivatives such as glabridin, galbrene, glabrone, shinptero-
carpin, licoisoflavones A and B, formononetin, glyzarin, kumatakenin have been
isolated and identified in 2003 by Williamson. In 2001, other researchers De
Simone et al. have reported hispaglabridin A, hispaglabridin B, 4′-
O-methylglabridin, and 3′-hydroxy-4′-O-methylglabridin from Glycyrrhiza species.
The licochalcone A has been isolated and identified from the ethyl acetate extract of
the roots of G. uralensis (Won et al. 2007). Kinoshita et al. (2005) have studied G.
glabra, and they identified several compounds from its roots such as glabridin,
galbrene, glabrone, shinpterocarpin, licoisoflavones A and B, formononetin, gly-
zarin, kumatakenin, hispaglabridin A, hispaglabridin B, glabroisoflavanone A, and
B glabroiso-flavanone B.
7.1 Phytochemistry of Components 49

7.1.2 Saponins

In the 1990s, Fenwick and his co-workers have described two aglycone forms of
glycyrrhizic acid, 18b-glycyrrhetinic acid and 18a-glycyrrhetinic acid. The
anti-inflammatory and antiarthritic activity in animal studies too have been followed
and attributed to the glycyrrhetic acid (Amirova 1993). A speedy healing of gastric
ulcers is attributed to the presence of glycyrrhizin and the aglycone of glycyrrhizin in
the liquorice (Amirova 1993; Blumenthal et al. 2000). Glycyrrhiza roots are reported
to contain triterpenoid saponins (glycyrrhizin, glycyrrhizic acid). These are the major
characteristic constituents of liquorice responsible for the sweet taste (Blumenthal
et al. 2000). The major triterpenoid saponin in the root of this plant is glycyrrhizic
acid. Latter is the main sweetener in this plant, nearly 50 times sweeter than sugar
(Nomura et al. 2002). Other triterpenes too have been reported namely liquiritic acid,
glycyrretol, glabrolide, isoglaborlide, and licorice acid (Isbrucker and Burdock
2006). The described several saponins have been reported by Zhang and Ye (2009)
from Glycyrrhiza species namely, licorice-saponin A3, 22b-actoxylglycyrhhizin,
uralsaponin B, apioglycyrrhizin, araboglycyrrhizin, and icorice-saponin E2. In 2013,
Vashist and Sharma have published data mentioning about the presence of ammo-
nium glycyrrhizinate (3.4%) and calcium glycyrrhizinate (4%) in the ethanolic
extract of G. glabra.

7.1.3 Phenolic Compounds

Nomura and Fukai (1998) have published several reports on the phenolic constituents
of Glycyrrhiza species. The main phenols include liquiritin, isoliquiritin, liquiritin
apioside, and isoprenoid-substituted flavonoids, chromenes, coumarins, dihydros-
tilbenes. For example, isobavachin has been reported from Glycyrrhiza pallidiflora,
sigmoidin B in G. uralensis, liquiritigenin in some Glycyrrhiza species by the same
workers. Nomura et al. (2002) have investigated several Glycyrrhiza species from the
point of view of phenolic compounds. They have found isoprenoid-substituted fla-
vonoid (pyranoisoflavan, glabridin) (G. glabra), isoflavans (G. uralensis), licochal-
cone A (G. inflata, Glycyrrhiza eurycarpa), licoricidin (6), and licorisoflavan A
(Glycyrrhiza aspera). Similar observations have been reported in 2003 by
Williamson. Latter identified liquiritin, liquiritigenin, rhamnoliquiritin, neoliquiritin,
chalcones isoliquiritin, isoliquiritigenin, neoisoliquiritin, licuraside, glabrolide, and
licoflavonol. In 2008, Zhu et al. worked on the biologically active compounds of G.
uralensis collected from Mongolia. They have reported 3 flavanone constituents
(liquiritin apioside, liquiritin, and liquiritigenin) and 3 chalcones (isoliquiritin apio-
side, isoliquiritin, and isoliquiritigenin). In 2009, Zhang and Ye described several
phenolic compounds derived from Glycyrrhiza species including glycycoumarin,
glabrocoumarin, glycyrin, inflacoumarin A, licopyranocoumarin, isoglycerol, neo-
glycerol, licobenzofuran, licocoumarone, glabrocoumarone, gancaonin, and
50 7 Pharmacological Activities and Phytochemical Constituents

kanzonol. Isolation and identification of isoliquiritigenin from Chinese liquorice have

been carried out by Chin et al. (2007) and liquiritin by Huang et al. (2010).
In a study by Ammar et al. (2012), the researchers have isolated phenolic
compounds namely liquiriteginin, liquiritin apioside, neoliquiritin apioside,
isoliquiritin, isoliquritin apioside, licuraside2-(5-P-coumaryl apiosyl), and
isoliquiritin from the total polar extract of G. glabra utilizing different chromato-
graphic techniques.
In an attempt to discover bioactive agents in G. glabra, 11 new phenolic com-
pounds, glycybridins A–K, along with 47 known phenolics have been isolated by Li
et al. (2017). They have conducted enzyme or cell-based bioactivity screenings of 1–
58 according to the clinical therapeutic effects of liquorice. A number of compounds
have been reported to significantly activate Nrf2, inhibit tyrosinase or PTP1B, inhibit
lipopolysaccharide-induced NO production and NF-jB transcription, and inhibit the
proliferation of human cancer cells (HepG2, SW480, A549, and MCF7).
Glycybridin D has shown moderate cytotoxic activities against the four cancer cell
lines, with IC50 values ranging from 4.6 to 6.6 lM (Li et al. 2017). Further studies
have indicated that Glycybridin D (10 mg/kg) decreases tumor mass by 39.7% on an
A549 human lung carcinoma xenograft mice model with little toxicity (Li et al. 2017).
These workers have carried out studies to discover bioactive natural products from
one botanical source of G. inflata. A total of 67 free phenolics have been isolated to
form a compound library. Based on the licorice bioactivity, these compounds have
been subjected to screening using cell- or enzyme-based bioassay methods. A total of
11 compounds have exhibited potent cytotoxic activities against 3 human cancer cell
lines (HepG2, SW480, and MCF7), but have shown little toxicity on human normal
cell lines LO2 and HEK293T. A number of chalcones have been observed to show
remarkable anti-inflammatory activities. Out of these, licochalcone B, IC50 8.78 µM,
licoagrochalcone C, IC50 9.35 µM, and licochalcone E, IC50 9.09 µM have
exhibited the most potent inhibitory activities on lipopolysaccharide-induced NO
production, whereas IC50 13.9, 7.27, 2.44, 6.67, and 3.83 µM have shown potent
inhibitory activities on NF-KB transcription. Nine prenylated phenolics have been
found to be PTP1B inhibitors. Particularly, licoagrochalcone A, kanzonol C, 2′-
hydroxyisolupalbigenin, gancaonin Q, glisoflavanone, and glabrol with IC50 values
of 0.31–0.97 µM. Compounds semilicoisoflavone B, IC50 0.25 µM, alloli-
coisoflavone B, IC50 0.80 µM, and glabridin, IC50 0.10 µM have shown noticeable
tyrosinase inhibitory activities (Lin et al. 2017). Most of the above bioactive com-
pounds have been reported for the first time by these workers.

7.1.4 Coumarins

The most important other constituents are coumarins including liqcoumarin,

glabrocoumarone A and B, herniarin, umbelliferone, glycyrin, glycocoumarin,
licofuranocoumarin, licopyranocoumarin, and glabrocoumarin. All are present in G.
glabra (De Simone et al. 2001; Haraguchi 2001; Williamson 2003; Kinoshita et al.
7.1 Phytochemistry of Components 51

2005). Also, four dihydrostilbenes-dihydro-3,5-dihydroxy-4′-acetoxy-5′-iso-

pentenylstilbene, dihydro-3,3′,4′-trihydroxy-5-O-isopentenyl-6-isopentenylstilbene,
dihydro-3,5,3′-trihydroxy-4′-thoxystilbene, and dihydro-3,3′-dihydroxy-5b-d-O-
glucopyranosyloxy-4′-methoxystilbene- have been isolated from the leaves of G.
glabra grown in Sicily (Biondi et al. 2005).
In 2014 Qiao and co-workers have identified glycerol, glycycoumarin, dehy-
droglyasperin in the root extract of G. uralensis. Two coumarins of G. glabra,
glycocoumarin and licopyranocoumarin, have also been described by De Simone
et al. (2001), these are able to inhibit giant cell formation in HIV-infected cell
cultures.

7.1.5 Essential Oils and Other Compounds

Nearly 3 decades ago, Frattini et al. (1977) reported 63 compounds never found
before in heated liquorice essential oil. They used GLC, GLC-MS coupling, and IR
spectrometry. In the same year, Frattini et al. (1977) found many heated liquorice
compounds, the furan derivatives. The reason given for this is pyrolysis and con-
densation reactions which occur during heating, when sugars in liquorice roots are
very rich. Acetol, propionic acid, 2-acetylpyrrole, Z-acetylfuran, and furfuryl
alcohol are the most abundant components. None of the identified compounds alone
are responsible for the flavor in liquorice. On the other hand, total extract shows a
typical liquorice aroma, possibly due to an integrated response to the proper mixture
of the proper volatiles, rather than to the odor of one or two components (Frattini
et al. 1977).
In 2006, Näf and Jaquier have studied the lactonic fraction of a commercial
liquorice root extract (G. glabra), exhibiting a pleasant sweet, woody, dried
fruit-like odor, containing mainly fatty acids (C2–C16) and phenols (phenol, gua-
iacol), together with common saturated linear c-lactones (C6–C14) and, in trace
amounts, a series of new 4-methyl-c-lactones and 4-ethyl-c-lactones. Other com-
pounds such as asparagines, glucose, sucrose, starch, polysaccharides (arabino-
galactants), and sterol (b-sitosterol, dihydrostigmasterol) have also been reported
(Hayashi et al. 1998; Blumenthal et al. 2000). Other secondary metabolites have
also been reported such as fatty acids, phenol, guaiacol, asparagines, glucose,
sucrose, starch, polysaccharides, and sterols (b-sitosterol, dihydrostigmasterol) (Näf
and Jaquier 2006).
In Turkey, the essential oil from aerial parts and roots of Glycyrrhiza taxa has been
analyzed by gas chromatography and mass spectroscopy (GC–MS) systems by
Çakmak (2011). The major components identified by him are listed as follows: hex-
anal, b-vii pinene, furan-2-pentyl, benzaldehyde, 4-terpineol, 1-pentylcyclobutene,
acetophenone, a-caryophyllen, naphtalene, 1-phenyl-1H-pyrazol-3-amine, m-cresol,
nerolidol, hexahydro farnesyl acetone, E-neryl linalool, 1-tetracosanol,
p-hexylacetophenone, phytol, 4-pyridinecarbonitrile, dimethylamine, and
n-hexadecanoic acid. Fatty acid profiles of these taxa have also been examined by
52 7 Pharmacological Activities and Phytochemical Constituents

GC-FID and 22 fatty acids are reported, palmitic, linoleic, and linolenic acid being the
main components (Çakmak 2011).
Farag and Wessjohann (2012) have undertaken investigations to provide insight
into Glycyrrhiza species aroma composition and for its use in food and pharma-
ceutical industry. They profiled volatile constituents from G. glabra, G. inflata, and
G. echinata roots using steam distillation and solid-phase microextraction. Two
phenols, thymol and carvacrol, have been found exclusively in essential oil and
headspace samples of G. glabra, and with highest amounts of samples that origi-
nated from Egypt. In G. echinata oil, (2E, 4E)-decadienal (21%) and
b-caryophyllene oxide (24%) have been reported as the main constituents, whereas
1a, 10a-epoxyamorpha-4-ene (13%), and b-dihydroionone (8%) have predomi-
nated G. inflata (Farag and Wessjohann 2012). Moreover, Farag and Wessjohann
(2012) have also reported that principal component and hierarchical cluster analyses
have clearly separated G. echinata and G. inflata from G. glabra, with phenolics
and aliphatic aldehydes contributing mostly for species segregation.
The essential oil composition of G. glabra has been investigated by Ali (2013).
He has reported compounds such as a-pinene, b-pinene, octanol, c-terpinene,
stragole, isofenchon, b-caryophyllene, citronellyl acetate, caryophyllene oxide, and
geranyl hexanolate. Out of these, geranyl hexanolate represents the higher per-
centage (34%) whereas b-pinene the lowest (1.7%). The phytoestrogens have been
investigated in the roots of G. glabra from Syria by Khalaf et al. (2010). They have
identified daidzein, daidzin, genistin, ononin, glycitein, genistein, and coumestrol,
whereas dihydrostilbenes from the root extract of G. glabra grown in Sicily has
been reported by Sultana et al. (2010).
Wagner et al. (2016) have studied the application of the molecular sensory
science concept including aroma extract dilution analysis (AEDA) on the basis of
gas chromatography-olfactometry combined with gas chromatography–mass
spectrometry. They elucidated the key odorants of raw liquorice (G. glabra) and
found 50 aroma-active compounds via AEDA; 16 of these have been identified in
raw liquorice for the first time. c-Nonalactone, 4-hydroxy-2,5-dimethylfuran-3(2H)-
one, and 4-hydroxy-3-methoxybenzaldehyde have shown the highest flavor dilution
(FD) factor of 1024. Nearly, 43 compounds have been quantified using stable
isotope dilution analysis (SIDA); 6 more compounds have been quantified using
labeled standards and odor activity values (OAVs), which is the ratio of concen-
tration to the respective odor threshold. OAVs have been calculated revealing
OAVs  1 for 39 compounds. The highest OAVs were shown by (E,Z)-
2,6-nonadienal, 5-isopropyl-2-methylphenol, hexanal, and linalool (Wagner et al.
2016). On the basis of the data obtained by these workers, an aqueous reconstitution
model has been prepared by mixing the 39 odorants in their naturally occurring
concentrations. The recombinate has elicited an aroma profile very similar to the
profile of raw liquorice, proving that all key aroma compounds have been correctly
identified and quantified (Wagner et al. 2016).
Ata et al. (2017) have studied the ion-pair extraction combined with liquid
chromatography–tandem mass spectrometry method. They have proposed the
determination of biogenic amines in liquorice samples (G. glabra). Their
7.1 Phytochemistry of Components 53

evaluations have revealed that limit of detection and limit of quantitation for the
biogenic amines are 1.4–2.7 and 4.7–9.1 ng mL−1, respectively. Relative standard
deviations based on 5 replicate extractions of 100 ng mL−1 of each biogenic amine
were <4.7% for intra-day and 7.4% for inter-day precision. The method described
by Ata et al. (2017) has been in accordance with the satisfactory accuracy and good
reproducibility for the quantitative determination of biogenic amines in liquorice
samples. Nine biogenic amines (putrescine, cadaverine, histamine, spermine,
spermidine, tyramine, tryptamine, agmatine, and phenylethylamine) have been
detected in liquorice samples and total biogenic amine concentrations have been
determined at 369 ng mL−1 in fresh and 3532 ng mL−1 in non-fresh samples.
Putrescine has been found at the highest concentrations—up to 704 ng mL−1 in all
the analyzed samples, followed by tyramine (675 ng mL−1) and tryptamine
(282 ng mL−1). Putrescine, tyramine, and spermine concentrations have dramati-
cally increased, whereas agmatine concentration has significantly decreased, in
non-fresh liquorice samples compared to fresh ones (Ata et al. 2017). Moreover,
they have reported that the consumption of freshly prepared liquorice is recom-
mended because of the relatively low concentration of total biogenic amines.
Ye et al. (2017) have examined the bioactive constituents of G. uralensis leaves.
Seven chemical components have been isolated by repeat column chromatography and
using spectroscopic methods. Their structures have been determined to be a novel
prenylated dihydrostilbene, a,a′-dihydro-3,5,3′,4′-tetrahydroxy-2,5′-diprenylstilbene,
a methylated flavonoid, quercetin-3-Me ether, and 5 prenylated flavonoids: 5′-pre-
nylquercetin, 8-[(E)-3-hydroxymethyl-2-butenyl]eriodictyol, 6-prenyleriodictyol, 5′-
prenyleriodictyol, and 6-prenylquercetin-3-Me ether. These compounds show strong
radical scavenging activity toward DPPH, and most of them have demonstrated greater
inhibitory activity against a-glucosidase than their unprenylated counterparts
(Ye et al. 2017).

7.2 Bioactive Components and Biological Functions

Liquorice is not used only in food, tobacco, and cosmetics, and it has great value in
medicine, because this herb is accepted as a herbal remedy for many disorders (Kao
et al. 2014). Some of its traditional uses like diabetes, cough, wound treatment, and
tuberculosis have been discussed by Asl and Hosseinzadeh (2008). It is also well
known as one of the most frequently used herbs in China, as it has been in use in
their traditional medicine for centuries. This herb is commonly used in herbal
formulas to harmonize other ingredients and applied under 12 regular meridians in
Chinese traditional medicine. As per the compendium of Materia Medica (Bencao
Gangmu) liquorice acts as an effective antidote, a detoxicant, a beneficial agent in
the development of bone and muscle, and a remedy for throat disorders and cough
(Li 2003). It is also included in many traditional Chinese medicine formulas for
treating liver disease. Similarly, in Japan sho-saiko-to (TJ-9) is used for liver dis-
orders (e.g., chronic active hepatitis), (Hirayama et al. 1989). This formula is said to
54 7 Pharmacological Activities and Phytochemical Constituents

have come from Xiao Chai Hu Tang (Minor Bupleurum Formula) in Shang Han
Lun of TCM (Chang 1981).
Recent investigations depict that in traditional Chinese medicine uses of licorice
vary much (Kao et al. 2014). A mixture of Ephedra, Cassia twig, bitter apricot
kernel, and liquorice, known as Ma Huang Tang––a classic Chinese Formula has
recently been confirmed to be effective in the treatment of pulmonary disorders like
bronchial asthma, acute bronchitis, colds, and influenza. Direct effects of the bitter
apricot kernel and liquorice are mentioned to be nonsignificant but, the two drugs
have a significant synergetic effect when administered with Ephedra or Cassia
twigs (He et al. 2012). This clearly shows that liquorice has ability to harmonize
with the other ingredients in the formula. Liquorice gargles are reported to be highly
effective in the incidence and severity of postoperative sore throat (Agarwal et al.
2009). This confirms the findings for its use in traditional Chinese medicine. Some
liquorice healing effects in the traditional Chinese medicine is fully confirmed by
modern medicine. However, we still need to enlighten the fact which compound(s)
in this herb mediate these effects (Kao et al. 2014).

7.2.1 Glycyrrhizic Acid and 18b-Glycyrrhetinic Acid

The sweetness of liquorice comes from glycyrrhizic acid or glycyrrhizin, a triter-

penoid saponin glycoside; 30–50 times sweeter than sucrose. It induces impulses
from sugar receptor-containing cells at a concentration (3.0 mM), much lower than
sucrose (Ahamed et al. 2001; Kao et al. 2014). Glycyrrhizin maintains its sweetness
after heating as against the sugar substitute aspartame. Although sugar and gly-
cyrrhizic acid taste sweet, but glycyrrhizic acid induces a lower onset sweet flavor
than sugar. Its sweetness remains in the mouth for a longer time (Kao et al. 2014).
Another triterpenoid in liquorice is glycyrrhetinic acid (18a-glycyrrhetinic acid and
18b-glycyrrhetinic acid) obtained from the hydrolysis of glycyrrhizic acid.
Presystemic metabolism by intestinal bacteria performing glycolysis can complete
this process (Ploeger et al. 2001). The glycyrrhizic acid is metabolized by human
intestinal bacteria through the action of the glucuronidases of Bacteroides J-37 and
Eubacterium sp. to yield 18b-glycyrrhetinic acid (18bGA) (Kim et al. 1999). In the
Chinese Materia Medica, dry-roasting or honey-roasting are the two processes used
to obtain liquorice preparation which accelerates the hydrolysis of the sugar chains
in the saponin and glycosidic flavonoid constituents (Sung and Li 2004; Kuwajima
et al. 1999). Both raw liquorice as well as liquorice preparata are important agents
in traditional Chinese medicine, each having different function. Anti-inflammatory
activities and neuroprotective effects of roasted form is said to be more potent than
raw one, which goes against the characteristics described by traditional Chinese
medicine (Hwang et al. 2006; Kim et al. 2010). As per “Bencao Gangmu” raw form
can be used to treat the syndrome known as inflammation in modern medicine (Xie
Huo in Chinese), and roasted form for reinforcement (Bu Zhong in Chinese) (Li
2003). The roasted form is used in Buzhong Yiqi Tang instead of raw, suggesting
7.2 Bioactive Components and Biological Functions 55

that glycyrrhizic acid and 18b-glycyrrhetinic acid may have distinct biological
characteristics (Kao et al. 2014).
This herb has also been used alone and as a component in many formulas to treat
liver diseases. Multiple mechanisms have been proposed for the hepatoprotective
effects of glycyrrhizic acid and 18b-glycyrrhetinic acid (Kao et al. 2014). The gly-
cyrrhizic acid and 18b-glycyrrhetinic acid are reported to have an ability to protect
hepatocytes from bile acid-induced cytotoxicity (Gumpricht et al. 2005). A beneficial
effect of glycyrrhizic acid on hepatitis has been demonstrated recently. The intra-
venous administration of glycyrrhizic acid is said to decrease serum alanine
transaminase (ALT) and necro-inflammation and fibrosis in the liver (Manns et al.
2012). The protective effects of glycyrrhizic acid and 18b-glycyrrhetinic acid are
controlled by several mechanisms, which likely are involved in the reduced AST
(aspartate transaminase, also called GOT) and ALT (also called GPT) activities. The
glycyrrhizic acid can also modulate the pregnane X receptor (PXR), as well as
cytochrome P450 family 3 subfamily A (CYP3A), to protect against lithocholic
acid-induced injury (Wang et al. 2012). The treatments with glycyrrhizic acid and
18b-glycyrrhetinic acid can inhibit liver fibrosis, which otherwise may lead to cancer
(Moro et al. 2008; Kao et al. 2014). Both may be effective in the protection of other
organs, as they have positive effects on brain damage induced by ischemia and
6-hydroxydopamine. A recent study has demonstrated that both of these can penetrate
the blood–brain barrier (BBB) indicating that they are potent agents for the treatment
of neural diseases, ischemic brain diseases, and Parkinson’s disease (Kao et al. 2009,
2014; Tabuchi et al. 2012). Glycyrrhizic acid also exhibits protective effects in the
kidney. It has been demonstrated that it protects against cisplatin-induced genotox-
icity and nephrotoxicity. The protective effects have also been observed with a renal
hypoxia-reoxygenation model, however 18b-glycyrrhetinic acid does not exhibit the
same potential (Yokozawa et al. 2000; Arjumand and Sultana 2011). Glycyrrhizic
acid seems to be effective against ischemic damage, including damage to the spinal
cord, myocardium, liver, and gut (Yokozawa et al. 2000; Di Paola et al. 2009;
Haleagrahara et al. 2011; Ogiku et al. 2011).
Glycyrrhizic acid and 18b-glycyrrhetinic acid are considered inhibitors of
inflammation induced by both bacterial and viral infection, as inflammation is
frequently triggered by bacteria or viral infection, and antibacterial and antiviral
activities are possible anti-inflammatory strategies. Former can inhibit the replica-
tion of and infection by various viruses (Fiore et al. 2008; Kao et al. 2014),
including severe acute respiratory syndrome (SARS)-associated coronavirus
(Cinatl et al. 2003), human immunodeficiency virus (HIV) (De Clercq 2000),
hepatitis A virus (HAV) (Crance et al. 1990), hepatitis B virus (HBV) (Takahara
et al. 1994), hepatitis C virus (HCV) (Orlent et al. 2006), herpesviridae (varicella
zoster virus, VZV) (Baba and Shigeta 1987), herpes simplex virus 1 (HSV-1)
(Lampi et al. 2001), Epstein–Barr virus (EBV) (Lin 2003), cytomegalovirus
(CMV) (Numazaki et al. 1994), and influenza viruses, including H1N1 (Pompei
et al. 1979) and H5N1 (Michaelis et al. 2011). The glycyrrhizic acid also inhibits
the growth of Helicobacter pylori, and thus can be used in the treatment of gastric
ulcers, 18bGA has also been shown to be effective against clarithromycin-resistant
56 7 Pharmacological Activities and Phytochemical Constituents

strains of H. pylori (Chung 1998; Krausse et al. 2004). Glycyrrhizic acid and
18b-glycyrrhetinic acid are also reported to modulate inflammation-related mech-
anisms. Traditional Chinese medicine often incorporates this herb to enhance the
effect of other formulas that act as anti-inflammatory agents. Anti-inflammatory
effect of liquorice extract is enhanced by glycyrrhizic acid without glycyrrhizic acid
(Uto et al. 2012). Glycyrrhizic acid is reported to possess an ability to inhibit
H5N1-induced proinflammatory gene expression without affecting the cytolytic
activity of natural killer cells (Michaelis et al. 2011). These findings depict that
glycyrrhizic acid probably modulates inflammation by two regulatory methods
namely, inhibition of proinflammatory cytokines and the promotion of immune
function. In this regulation PI3K probably plays a role. The inflammation is very
effectively modulated by glucocorticoids and the glucocorticoid receptor, latter is
extensively used in clinical treatments (e.g., dexamethasone). Several potential
mechanisms exist for the involvement of glycyrrhizic acid and 18b-glycyrrhetinic
acid in the induction of cortisone activity. The two can activate glucocorticoid
receptor (GR) signaling by binding to the GR and inhibit the activity of corticos-
teroid 11b-dehydrogenase isozyme 2 (11b-HSD2), which converts active cortisol
into inactive cortisone (Whorwood et al. 1993; Kao et al. 2010; Ma et al. 2011).
Both may also enhance GR signaling by eliminating intracellular oxidative stress
(Kao et al. 2013). No increase in the glucocorticoid-induced side effects is seen,
although glycyrrhizic acid enhances glucocorticoid activity. Excessive glucocorti-
coid levels are reported to exert diverse effects on bone microstructure, integrity,
and mineral metabolism (Iba et al. 1995). It has been demonstrated that glycyrrhizic
acid has the potential for use as an agent to protect the bones against
glucocorticoid-induced osteoporosis (Ramli et al. 2013). A nuclear component
(high-mobility group box 1 (HMGB1) that functions extracellularly as a signaling
molecule in acute and chronic inflammation has been reported to get inhibited by
binding to glycyrrhizic acid (Mollica et al. 2007). According to Kao et al. (2013),
glycyrrhizic acid and 18b-glycyrrhetinic acid can modulate PI3K signaling to
alleviate inflammation. All these results demostrate that glycyrrhizic acid and
18b-glycyrrhetinic acid possess considerable potential for development as novel
inflammation-modulating agents (Kao et al. 2014).
They can also affect the biological mechanism of cancer formation. Glycyrrhizic
acid may inhibit angiogenesis by targeting ERK signaling, and can be protective
against UV-B-induced carcinogenesis in the epidermis of SKH-1 hairless mice
(Cherng et al. 2011; Kim et al. 2013). GA also prevents hepatocarcinogenesis
associated with hepatitis because it is effective against HCV-induced liver disorders
(Ikeda et al. 2006; Ikeda 2007). AS compared to GA glycyrrhetinic acid has a more
potent anticarcinogenesis effect. According to Lee et al. (2008), 18b-glycyrrhetinic
acid not only induces apoptotic cell death but also exhibits a synergistic toxic effect
with antibiotics and anticancer drugs like camptothecin, mitomycin c, and dox-
orubicin. The report published by Farina et al. (1998) reports that glycyrrhetinic
acid, oleanolic acid, and ursolic acid have similar chemical structures and potent
antiulcer activities. A satisfactory anticarcinogenesis outcome is found in the
compounds whose chemical structures are similar to that of glycyrrhetinic acid
7.2 Bioactive Components and Biological Functions 57

(Csuk et al. 2011). The glycyrrhetinic acid and its derivatives are highly effective in
the treatment of many cancer cells as they are sensitive to treatment, including
human epithelial ovarian carcinoma cell lines OVCAR-3 and SK-OV-3 (Lee et al.
2010a; Yang et al. 2012), the human prostate cancer cell lines DU145 (Shetty et al.
2011; Szpak et al. 2011) and PC3, the human breast cancer cell line MCF7 (Sharma
et al. 2012; Zhao et al. 2012), the human bladder cancer cell line NTUB1 (Lin et al.
2011), the human leukemia cell line HL60 (Gao et al. 2010), the human ery-
thromyeloblastoid leukemia cell line K562 (Song et al. 2010), the human colon
cancer cell lines RKO and SW480 (Chintharlapalli et al. 2009), the pancreatic
cancer cell lines Panc1 and Panc28 (Jutooru et al. 2009), and many other cell lines.
18b-glycyrrhetinic acid is more toxic than glycyrrhizic acid, glycyrrhizic acid
displays no obvious cell toxicity, even at 200 lM (Kao et al. 2009, 2010, 2013).
DNA and RNA binding has been observed in both GA as well as glycyrrhetinic
acid (Nafisi et al. 2012a, b), which implies that both may directly interfere with the
pattern of transcription factors, the targeting of gene expression, and the interactions
of DNA and RNA. This is a promising research topic for understanding the bio-
logical functions of these two. Glycyrrhizic acid and 18b-glycyrrhetinic acid have
distinct biological functions, which may be due to the differences in their chemical
structures (Kao et al. 2014).

7.2.2 Liquiritin, Isoliquiritin, Liquiritigenin,

and Isoliquiritigenin

The first two are the chalconoids of liquorice, whereas other two are the glycone
forms of the former respectively (Kao et al. 2014). Studies on their antioxidant
abilities are limited. These compounds are reported to be the potent protective
agents against cancer and all four compounds may have a potent antispasmodic
effect (Lee et al. 2013). These four compounds are said to play an important role in
healing effects, their chemical structures are similar, a simultaneous study on these
compounds may facilitate the elucidation of the relationship between their bio-
logical effects and structure (Kamei et al. 2005; Kao et al. 2014).
The biological functions of liquiritin are similar to those of glycyrrhizic acid.
Liquiritin promotes neurite outgrowth in PC12 cells with nerve growth factor
treatment (Chen et al. 2009), suggesting its potential as a remedy for neurode-
generative diseases such as Alzheimer’s disease or Parkinson’s disease.
Furthermore, liquiritin may exhibit an antidepressant-like effect in chronic variable
stress-induced depression model rats by modulating oxidative stress (Zhao et al.
2008). It proves beneficial in patients with diabetes mellitus because it attenuates
the induction of the RAGE/NFjB pathway in human umbilical vein endothelial
cells (HUVECs) by advanced glycation end products (AGE), (Zhang et al. 2013).
According to Cheel et al. (2010), liquiritin and glycyrrhizic acid can stimulate
immune responses, enhance antioxidant enzymes like superoxide dismutases
(SOD), catalase, and glutathione peroxidase in mice focal cerebrum (Sun et al.
58 7 Pharmacological Activities and Phytochemical Constituents

2010). These may act as protective agents against epithelial injury in chronic
obstructive pulmonary disease (COPD) (Guan et al. 2012). Liquiritin may bind to
DNA like glycyrrhizic acid (Gao et al. 2009) and may directly affect gene
expression or other DNA-related mechanisms. Both are glycones or glycosides, the
functional groups important for DNA binding, but this characterization is yet to be
confirmed (Kao et al. 2014).
Not much work is done on isoliquiritin listed in the PubMed database, because
of its lack of commercial availability, most of the data published deals with its
isolation and identification (Kao et al. 2014). It is thought to prevent angiogenesis
and tube formation in granulomas and may also have a potent antitussive effect
(Kobayashi et al. 1995; Kamei et al. 2003). Its other possible application is skin
depigmentation due to tyrosinase inhibition (Fu et al. 2005).
Liquiritigenin is a well-known selective estrogen receptor b agonist implicated in
the weight-reducing effects of liquorice oil (Mersereau et al. 2008; Jungbauer and
Medjakovic 2014). It facilitates the recovery of learning and memory deficits
induced by amyloid beta Ab(25-35) and also helps to enhance osteoblast function
(Liu et al. 2010; Choi 2012). Liquiritigenin as well as isoliquiritigenin are able to
inhibit xanthine oxidase, a promoting factor in many disorders (Kong et al. 2000).
The IC50 values of these compounds are 49.3 and 55.8 lM for liquiritigenin and
isoliquiritigenin respectively. Both are effective anti-inflammatory agents displaying
potential PPARc activating activity, suggesting their potential for use in recovery
from metabolic syndrome (Zhou et al. 2009). Latter is also an inhibitor of aldose
reductase, suggesting it might be effective in treating diabetic complications (Aida
et al. 1990). Liquiritigenin inhibits iNOS and proinflammatory cytokines by
blocking NFjB (Kim et al. 2008), while isoliquiritigenin is involved in the inter-
cellular adhesion molecule-1 (ICAM-1) and the vascular cell adhesion molecule-1
(VCAM-1) to modulate inflammation (Tanaka et al. 2001). Liquiritigenin has a
protective role against a number of injuries in many cells and organs, including
acetaminophen-induced rat liver damage, cadmium-induced rat hepatoma Reuber
H35 cell (H4IIE) damage, D-galactosamine/ lipopolysaccharide- or CCl4-mediated
rat hepatitis, Ab(25-35)-induced injury of rat hippocampal neurons, and infection by
Candida albicans (Kim et al. 2004, 2006; Lee et al. 2009; Liu et al. 2009; Kang et al.
2010a). On the other hand isoliquiritigenin also protects cells and organs by
inhibiting cisplatin-induced rat anorexia, the diabetes-induced hyperaggregability of
platelets, the accumulation of cyclic AMP in rat ventricular heart muscle, and by
potently promoting neuronal health by inhibiting monoamine oxidase A and B
among other mechanisms (Tawata et al. 1992; Wegener and Nawrath 1997; Pan
et al. 2000; Takeda et al. 2008). Liquiritigenin can enhance bile secretion in the liver
through choleretic effect and can enhance the activity of transporters and phase II
enzymes in the liver, which is thought to be related to the antidote ability of liquorice
(Kim et al. 2009). In addition to an increase in the bile secretion, it might increase the
rate of hepatic blood flow, and may exhibit chemopreventive activity in liver and
lung cancers (Zhang et al. 2009; Jayaprakasam et al. 2009; Kang et al. 2010b; Zhou
et al. 2010). The mechanisms by which it modulates chemoprevention may involve
apoptotic molecular targets, like cytochrome c, caspases, matrix metalloproteinases
7.2 Bioactive Components and Biological Functions 59

(MMPs), PI3K, Akt, and vascularization (Liu et al. 2011, 2012; Xie et al. 2012).
C8-prenylation of a flavonoid such as liquiritigenin may enhance the induction of
H4IIE and C6 glioma cell apoptosis without affecting its antioxidative properties
(Watjen et al. 2007). This compound has been reported to inhibit lipoxygenase and
prostaglandin E2 (PEG2), induce cell cycle arrest in the human prostate cancer cell
lines DU145 and LNCaP cells, induce cell death in the human breast cancer cell line
MCF7 at high concentration, suppress pulmonary metastasis of mouse renal cell
carcinoma, inhibit human lung cancer cell growth, inhibit colon cancer in ddY mice,
induce apoptosis in human MGC803 gastric cancer cells, and activate the apoptosis
in hepatoma cells among other effects in cancer cell, and therefore liquiritigenin is a
potent protectant in cells and organs, whereas isoliquiritigenin exhibits greater
potential in cancer chemoprevention (Yamamoto et al. 1991; Ma et al. 2001; Baba
et al. 2002; Maggiolini et al. 2002; Yamazaki et al. 2002; Kanazawa et al. 2003;
Takahashi et al. 2004; Ii et al. 2004; Hsu et al. 2005a, b; Kao et al. 2014).
Both these compounds have also been applied in the treatment of cocaine
addiction, but the results are preliminary. Liquiritigenin improves the selective
molecular and behavioral disorders associated with cocaine use and isoliquiritigenin
inhibits the dopamine release induced by cocaine (Jang et al. 2008, 2011). This
research has high practical value and is worth further study (Kao et al. 2014).

7.2.3 Dehydroglyasperin C and D

Dehydroglyasperin is an isoflavonoid isolated from licorice that has two isoforms,

dehydroglyasperin C (DGC) and dehydroglyasperin D (DGD). These two are clas-
sified as phenylflavonoids and are strong antioxidants, although the potency of DGC
is greater. The isoangustone A, another phenylflavonoid has also been identified, with
lower antioxidant activity than that of DGD (Lee et al. 2010b, c; Kim et al. 2012a).
Both DGC as well as DGD are potent ligands of peroxisome proliferator-activated
receptor c (PPARc), which is thought to play a role in metabolic syndrome. The
liquorice ethanolic extract containing DGC and DGD when used for the treatment in
KK-Ay and obese C57BL mice has been observed to prevent and ameliorate meta-
bolic syndrome in diabetic forms (Mae et al. 2003). According to Seo et al. (2010),
DGC is not only a ligand of PPARc but also an activating factor of Nrf2 and
detoxifying enzymes. It also modulates PI3K/Akt and Nrf2-Keap1 to protect against
glutamate-induced neuronal cell damage (Kim et al. 2012b). Both DGC and DGD are
relatively newly isolated compounds from liquorice and exhibit various potent
activities, but further study of their biology and toxicity is needed (Kao et al. 2014).

7.2.4 Glabridin

Another isoflavonoid reported from liquorice is glabridin with a structure similar to

estradiol-17b, and showing antimicrobial and antioxidant features (Mitscher et al.
60 7 Pharmacological Activities and Phytochemical Constituents

1980; Okada et al. 1989). It is frequently used in oxidative stress studies, including
LDL oxidation due to its well-described antioxidant capabilities (Belinky et al.
1998). Glabridin might modulate bone disorders in postmenopausal women and
increase osteoblastic cell function (Somjen et al. 2004; Choi 2005). Although a
potent antioxidant, its brain penetration through the BBB is altered by
p-glycoprotein, which might limit its application in central nervous system
(CNS) diseases (Yu et al. 2007). The main application of glabridin seems to be in
cosmetics. The antioxidant ability can help to modulate anti-inflammatory mecha-
nisms in skin tissue (Kao et al. 2014). The clinical studies are lacking however, some
commercial formulations with liquorice extract claim that glabridin is useful for skin
depigmentation (Leyden et al. 2011). According to Jirawattanapong et al. (2009),
glabridin and its derivatives inhibit tyrosinase. There are reports of a reduction in
UV-B-induced pigmentation and erythema in brownish guinea pigs after glabridin
administration for 3 weeks following UV-B irradiation (Yokota et al. 1998). In
addition to this potent anti-inflammatory activity, it has been reported to inhibit
inducible nitric oxide synthase (iNOS) expression and upregulate manganese SOD,
catalase, and paraoxonase 2 expression (Kang et al. 2005; Yehuda et al. 2011).
Many evidence indicate that this compound may be beneficial in the treatment of
diabetes mellitus and related diseases. Glabridin is found in the liquorice flavonoid
oil (LFO, also called Kaneka glavonoid-rich oil) as a bioactive flavonoid. It is
reported to suppress abdominal fat accumulation and blood glucose levels in
KK-Ay mice (Nakagawa et al. 2004). Licorice flavonoid oil (LFO) can activate
AMP-activated protein kinase (AMPK) and ameliorate the increases in fatty liver
and in the triglyceride and cholesterol plasma levels induced by obesity (Lee et al.
2012). If administered daily up to 1200 mg/day it is accepted as safe in humans
(Aoki et al. 2007). LFO seems to be as safe as a functional food. Glabridin also is
involved in the cancer prevention, because it blocks FAK/Rho signaling in human
nonsmall cell lung cancer A549 cells and inhibits the migration, invasion, and
angiogenesis of A549 cells (Tsai et al. 2011). In view of this, uses of glabridin
beyond cosmetics need to be explored (Kao et al. 2014).

7.2.5 Carbenoxolone

Carbenoxolone or CBX known as sodium carbenoxolone is the 3-hemisuccinate of

glycyrrhetinic acid, with a chemical structure similar to that of glucocorticoids. It
may be the best-known derivative of glycyrrhetinic acid, because the disodium salt
of the 3-o-hydrogen succinate, carbenoxolone is freely soluble in water (Lennon and
Lennard 1964). According to the report published by Connors in 2012, CBX can be
used as an anti-inflammatory agent and an inhibitor of 11b-hydroxysteroid dehy-
drogenase type 1. Its most important characteristic is sterol regulation, which is
involved in its effectiveness in the prevention of fatty liver (Rhee et al. 2012). This
compound might have a nootropic effect due to the regulatory ability of glucocor-
ticoids, thus improving verbal fluency and verbal memory in humans (Sandeep et al.
7.2 Bioactive Components and Biological Functions 61

2004). The quotes from traditional Chinese medicine “Bencao Gangmu” state that
liquorice consumption may enhance memory. Its best-known modern application is
for the treatment for gastric ulcer, which is based on the spironolactone, and has a
good outcome in aphthous ulcers (Doll et al. 1968; Porter and Scully Cbe 2007).
It is also a well-known gap junction inhibitor, widely used in neuroscience
research (Davidson et al. 1986). Gap junctions are also important in
glutamate-induced neurotoxicity, and carbenoxolone can decrease the toxic effects
of glutamate (Ozog et al. 2002). This compound is said to show a protective role
against ischemic injury in skeletal muscle and the hippocampus resulting from gap
junction inhibition (Hosseinzadeh et al. 2005). The gap junctions are also related to
pain control. The reason being the spinal cord glia exhibits extensive gap junctional
connectivity, which is involved in the contralateral spread of excitation resulting in
mirror image pain (Spataro et al. 2004). Carbenoxolone is also an inhibitor of gap
junctions, its application in pain relief seems reasonable. Connexin gap junction
proteins (Cx43 and Cx26) initiate brain metastatic lesion formation in association
with the vasculature. It can prevent tumor cell extravasation and blood vessel
involvement (Stoletov et al. 2013) and is frequently used in cancer research to probe
the relationship between gap junctions and cancer formation. A typical study is the
relationship between gap function and breast cancer metastasis or melanoma brain
colonization (Stoletov et al. 2013). This compound looks like a useful agent for
many research fields and is widely applied in clinical treatments (Kao et al. 2014).

References

Afreen F, Zobayed SMA, Kozai T (2005) Spectural quality and UV-B stress stimulate glycyrrhizin
concentration of Glycyrrhiza uralensis in hydroponic and pot system. Plant Physiol Biochem
43:1074–1081
Agarwal A, Gupta D, Yadav G, Goyal P, Singh PK, Singh U (2009) An evaluation of the efficacy
of licorice gargle for attenuating postoperative söre throat: a prospective, randomized,
single-blind study. Anesth Analg 109:77–81
Ahamed A, Tsurumi S, Ozaki M, Amakawa T (2001) An artificial sweetener stimulates the sweet
taste in insect: dual effects of glycyrrhizin in Phormia regina. Chem Senses 26:507–515
Aida K, Tawata M, Shindo H, Onaya T, Sasaki H, Yamaguchi T, Chin M, Mitsuhashi H (1990)
Isoliquiritigenin: a new aldose reductase inhibitor from glycyrrhizae radix. Planta Med 56:
254–258
Akhtar N, Khan MS, Iqbal A, Khan BA, Bashir S (2011) Glycyrrhiza glabra extract cream: effect
on skin pigment melanin. In: Proceeding book of International Conference on Bioscience,
Biochemistry and Bioinformatics, IPCBEE, IACSIT Press, Singapore
Ali EM (2013) Phytochemical composition, antifungal, antiaflatoxigenic, antioxidant, and
anticancer activities of Glycyrrhiza glabra L. and Matricaria chamomilla L. essential oils.
J Med Plants Res 7(29):2197–2207
Altay V, Karahan F, Öztürk M, Hakeem KR, Ilhan E, Erayman M (2016) Molecular and
ecological investigations on the wild populations of Glycyrrhiza L. taxa distributed in the East
Mediterranean Area of Turkey. J Plant Res 129(6):1021–1032
Ambawade S, Kasture VS, Kasturi SB (2001) Anxiolytic activity of Glycyrrhiza glabra Linn.
J. Nat. Remedies 2:130–134
62 7 Pharmacological Activities and Phytochemical Constituents

Amirova GS (1993) Licorice in Azerbaijan (in Russian). Elm, Baku, 104 pp

Ammar NM, El-Hawary SSED, El-Anssary AA, Othman N, Galal M, El-Desoky AH (2012)
Phytochemical and clinical studies of the bioactive extract of Glycyrrhiza glabra L. Family
Leguminosae. Int J Phytomed 4(3):429
Aoki F, Nakagawa K, Kitano M, Ikematsu H, Nakamura K, Yokota S, Tominaga Y, Arai N,
Mae T (2007) Clinical safety of licorice flavonoid oil (LFO) and pharmacokinetics of glabridin
in healthy humans. J Am Coll Nutr 26:209–218
Arjumand W, Sultana S (2011) Glycyrrhizic acid: a phytochemical with a protective role against
cisplatin-induced genotoxicity and nephrotoxicity. Life Sci 89:422–429
Asl NM, Hosseinzadeh H (2008) Review of pharmacological effects of Glycyrrhiza sp. and its
bioactive compounds. Phytother Res 22(6):709–724
Asl MN, Hosseinzadeh H (2012) Licorice (Glycyrrhiza species). In: Singh R (ed) Genetic
resources, chromosome engineering and crop improvement: medicinal plants, vol 6. CRC
Press, LLC, Taylor & Francis, USA, pp 935–958
Ata Ş, Akyüz M, Çabuk H (2017) Determination of biogenic amines in licorice (Glycyrrhiza
glabra) by ion-pair extraction and liquid chromatography-tandem mass spectrometry. J Sci
Food Agric 97:1427–1432
Baba M, Shigeta S (1987) Antiviral activity of glycyrrhizin against varicella-zoster virus in vitro.
Antiviral Res 7:99–107
Baba M, Asano R, Takigami I, Takahashi T, Ohmura M, Okada Y, Sugimoto H, Arika T,
Nishino H, Okuyama T (2002) Studies on cancer chemoprevention by traditional folk
medicines XXV. Inhibitory effect of isoliquiritigenin on azoxymethane-induced murine colon
aberrant crypt focus formation and carcinogenesis. Biol Pharm Bull 25:247–250
Belinky PA, Aviram M, Mahmood S, Vaya J (1998) Structural aspects of the inhibitory effect of
glabridin on LDL oxidation. Free Radic Biol Med 24:1419–1429
Biondi DM, Rocco C, Ruberto G (2005) Dihydrostilbene derivatives from Glycyrrhiza glabra
leaves. J Nat Prod 68:1099–1102
Blumenthal M, Goldberg A, Brinckmann J (2000) Herbal medicine: expanded commission E
monographs. Integrative Medicine Communications, Newton
Cai Y, Luo Q, Sun M, Corke HA (2004) Antioxidant activity and phenolic compounds of 112
traditional Chinese medicinal plants associated with anticancer. Life Sci 74:2157–2184
Çakmak YS (2011) Determination of chemical composition by using chromatographic techniquies
and antioxidant capacities of Glycyrrhiza L. species in Turkey. Ph.D. Thesis, The Graduate
School of Natural and Applied Science of Selçuk University, Konya-Turkey
Chakravarthi KK, Vadhani RA, Narayan RS (2012) Effect of Glycyrrhiza glabra root extract on
learning and memory in wistar albino rats. Int J Biol Med Res 3(3):2059–2064
Chang C (1981) c.f. Shang Han Lun. Oriental Healing Arts Institute, Los Angeles
Cheel J, Onofre G, Vokurkova D, Tumova L, Neugebauerova J (2010) Licorice infusion: chemical
profile and effects on the activation and the cell cycle progression of human lymphocytes.
Pharmacogn Mag 6:26–33
Chen ZA, Wang JL, Liu RT, Ren JP, Wen LQ, Chen XJ, Bian GX (2009) Liquiritin potentiate
neurite outgrowth induced by nerve growth factor in PC12 cells. Cytotechnology 60:125–132
Cherng JM, Tsai KD, Yu YW, Lin JC (2011) Molecular mechanisms underlying chemopreventive
activities of glycyrrhizic acid against UV-B-radiation-induced carcinogenesis in SKH-1
hairless mouse epidermis. Radiat Res 176:177–186
Chin YW, Jung HA, Liu Y, Su BN, John A, Castoro WJ, Keller MA, Douglas K (2007) Anti
oxidant constituents of the roots and stolons of licorice (Glycyrrhiza glabra). J Agric Food
Chem 55(1):4691–4696
Chintharlapalli S, Papineni S, Abdelrahim M, Abudayyeh A, Jutooru I, Chadalapaka G, Wu F,
Mertens-Talcott S, Vanderlaag K, Cho SD, Smith R III, Safe S (2009) Oncogenic
microRNA-27a is a target for anticancer agent methyl 2-cyano-3,11-dioxo-18beta-olean-1,
12-dien-30-oate in colon cancer cells. Int J Cancer 125:1965–1974
Choi EM (2005) The licorice root derived isoflavan glabridin increases the function of osteoblastic
MC3T3-E1 cells. Biochem Pharmacol 70:363–368
References 63

Choi EM (2012) Liquiritigenin isolated from Glycyrrhiza uralensis stimulates osteoblast function
in osteoblastic MC3T3-E1 cells. Int Immunopharmacol 12:139–143
Chopra PKPG, Saraf BD, Inam F et al (2013) Antimicrobial and antioxidant activities of methanol
extract roots of Glycyrrhiza glabra and HPLC analysis. Int J Pharm Pharmacol Sci 5(2):
157–160
Christensen SB, Kharazmi A (2001) Antimalarial natural products. In: Tringali C (ed) Bioactive
compounds from natural sources: isolation, characterization and biological properties. Taylor
and Francis, New York, pp 379–432
Chung JG (1998) Inhibitory actions of glycyrrhizic acid on arylamine N-acetyltransferase activity
in strains of Helicobacter pylori from peptic ulcer patients. Drug Chem Toxicol 21:355–370
Cinatl J, Morgenstern B, Bauer G, Chandra P, Rabenau H, Doerr HW (2003) Glycyrrhizin, an
active component of liquorice roots, and replication of SARS-associated coronavirus. Lancet
361:2045–2046
Connors BW (2012) Tales of a dirty drug: carbenoxolone, gap junctions, and seizures. Epilepsy
Curr 12:66–68
Crance JM, Biziagos E, Passagot J, van Cuyck-Gandre H, Deloince R (1990) Inhibition of
hepatitis A virus replication in vitro by antiviral compounds. J Med Virol 31:155–160
Csuk R, Schwarz S, Siewert B, Kluge R, Strohl D (2011) Synthesis and antitumor activity of ring
A modified glycyrrhetinic acid derivatives. Eur J Med Chem 46:5356–5369
Da Nagao Y, Sata M, Suzuki H, Tanikawa K, Itoh K, Kameyama T (1996) Effectiveness of
glycyrrhizin for oral lichen planus in patients with chronic HCV infection. J Gastroenterol
31:691–695
Davidson JS, Baumgarten IM, Harley EH (1986) Reversible inhibition of intercellular junctional
communication by glycyrrhetinic acid. Biochem Biophys Res Commun 134:29–36
De Clercq E (2000) Current lead natural products for the chemotherapy of human immunode-
ficiency virus (HIV) infection. Med Res Rev 20:323–349
De Simone F, Aquino R, De Tommasi N, Mahmood N, Piacente S, Pizza C (2001) Anti-HHIV
aromatic compounds from higher plants. In: Tringali C (ed) Bioactive compounds from natural
sources: isolation, characterization and biological proporties. Taylor & Francis Inc., New York,
p 325
Di Paola R, Menegazzi M, Mazzon E, Genovese T, Crisafulli C, Dal Bosco M, Zou Z, Suzuki H,
Cuzzocrea S (2009) Protective effects of glycyrrhizin in a gut hypoxia (ischemia)-
reoxygenation (reperfusion) model. Intensive Care Med 35:687–697
Dobrea C (2016) Liquiritiae radix and possible substituents—comparative LC/MS analysis of
specific flavonoids. AMT 21(4):111–113
Doll R, Langman MJ, Shawdon HH (1968) Treatment of gastric ulcer with carbenoxolone:
antagonistic effect of spironolactone. Gut 9:42–45
Farag MA, Wessjohann LA (2012) Volatiles profiling in medicinal licorice roots using steam
distillation and solid-phase microextraction (SPME) coupled to chemometrics. J Food Sci 77
(11):179–184
Farina C, Pinza M, Pifferi G (1998) Synthesis and anti-ulcer activity of new derivatives of
glycyrrhetic, oleanolic and ursolic acids. Farmaco 53:22–32
Fenwick GR, Lutomski J, Nieman C (1990) Liquorice, Glycyrrhiza glabra L.—composition, uses
and analysis. Food Chem 38:119–143
Fiore C, Eisenhut M, Krausse R, Ragazzi E, Pellati D, Armanini D, Bielenberg J (2008) Antiviral
effects of Glycyrrhiza species. Phytother Res 22:141–148
Firn R (2010) Nature’s chemicals: the natural products that shaped our world. Oxford University
Press, Oxford, pp 74–75
Franceschelli S, Pesce M, Vinciguerra I, Ferrone A, Riccioni G, Antonia P et al (2011)
Licocalchone-C extracted from Glycyrrhiza glabra inhibits lipopolysaccharide-interferon-c
inflammation by improving antioxidant conditions and regulating inducible nitric oxide
synthase expression. Molecules 16(7):5720–5734
Frattini C, Bicchi C, Barettini C, Nano GM (1977) Volatile flavor components of licorice. J Agric
Food Chem 25(6):1238–1241
64 7 Pharmacological Activities and Phytochemical Constituents

Fu B, Li H, Wang X, Lee FS, Cui S (2005) Isolation and identification of flavonoids in licorice and
a study of their inhibitory effects on tyrosinase. J Agric Food Chem 53:7408–7414
Fujisawa Y, Sakamoto M, Matsushita M, Fujita T, Nishioka K (2000) Glycyrrhizin inhibits the
lytic pathway of complement-possible mechanism of its anti-inflammatory effect on liver cells
in viral hepatitis. Microbiol Immunol 44:799–804
Fukai T, Satoh K, Nomura T, Sakagami H (2003) Preliminary evaluation of antinephritis and
radical scavenging activities of glabridin from Glycyrrhiza glabra. Fitoterapia 74(7):624–629
Gao W, Li K, Yan S, Gao X, Hu L (2009) Effects of space flight on DNA mutation and secondary
metabolites of licorice (Glycyrrhiza uralensis Fisch.). Sci China, Ser C Life Sci 52:977–981
Gao Y, Guo X, Li X, Liu D, Song D, Xu Y, Sun M, Jing Y, Zhao L (2010) The synthesis of
glycyrrhetinic acid derivatives containing a nitrogen heterocycle and their antiproliferative
effects in human leukemia cells. Molecules 15:4439–4449
Guan Y, Li FF, Hong L, Yan XF, Tan GL, He JS, Dong XW, Bao MJ, Xie QM (2012) Protective
effects of liquiritin apioside on cigarette smoke-induced lung epithelial cell injury. Fundam
Clin Pharmacol 26:473–483
Gumpricht E, Dahl R, Devereaux MW, Sokol RJ (2005) Licorice compounds glycyrrhizin and 18
beta-glycyrrhetinic acid are potent modulators of bile acid-induced cytotoxicity in rat
hepatocytes. J Biol Chem 280:10556–10563
Gupta VK, Fatima A, Faridi U, Negi AS, Shanker K, Kumar JK, Rahuja N, Luqman S,
Sisodia BS, Saikia DS, Darokar MP, Khanuja SPS (2008) Antimicrobial potential of
Glycyrrhiza glabra roots. J Ethnopharm 116:377–380
Haleagrahara N, Varkkey J, Chakravarthi S (2011) Cardioprotective effects of glycyrrhizic acid
against isoproterenol-induced myocardial ischemia in rats. Int J Mol Sci 12:7100–7113
Haraguchi H (2001) Antioxidative plant constituents. In: Tringali C (ed) Bioactive compounds
from natural sources: isolation, characterization and biological proporties. Taylor & Francis
Inc., New York, pp 348–352
Hatano T, Takagi M, Ito H, Yoshida T (1998) Acylated flavonoid glycosides and accompanying
phenolics from licorice. Phytochemistry 47:287–293
Hayashi H, Hiraoka N, Ikeshiro Y, Yamamoto H, Yoshikawa T (1998) Seasonal variation of
glycyrrhizin and isoliquiritigenin glycosides in the root of Glycyrrhiza glabra L. Biol Pharm
Bull 21(9):987–989
He Y, Gai Y, Wu X, Wan H (2012) Quantitatively analyze composition principle of Ma Huang
Tang by structural equation modeling. J Ethnopharmacol 143:851–858
Herz W, Kirby GW, Moore RE, Steglich W, Tamm C (1998) Fortschritte der Chemie Organischer
Naturstoffe, vol 73. Springer, New York
Hirayama C, Okumura M, Tanikawa K, Yano M, Mizuta M, Ogawa N (1989) A multicenter
randomized controlled clinical trial of Shosaiko-to in chronic active hepatitis. Gastroenterol Jpn
24:715–719
Hoffmann D (1990) The new holistic herbal, 2nd edn. Element, Shaftesbury
Hossain MS, Hossain MA, Islam R, Alam AH, Zahan K, Sarkar S, Farooque MA (2004)
Antimicrobial and cytotoxic activities of 2-aminobenzoic acid and 2-aminophenol and their
coordination complexes with Magnesium (Mg-II). Pak J Biol Sci 7:25–27
Hosseinzadeh H, Nassiri Asl M, Parvardeh S (2005) The effects of carbenoxolone, a semisynthetic
derivative of glycyrrhizinic acid, on peripheral and central ischemia-reperfusion injuries in the
skeletal muscle and hippocampus of rats. Phytomedicine 12:632–637
Hsu YL, Kuo PL, Lin LT, Lin CC (2005a) Isoliquiritigenin inhibits cell proliferation and induces
apoptosis in human hepatoma cells. Planta Med 71:130–134
Hsu YL, Kuo PL, Lin CC (2005b) Isoliquiritigenin induces apoptosis and cell cycle arrest through
p53-dependent pathway in Hep G2 cells. Life Sci 77:279–292
Huang M, Wang W, Wei S (2010) Investigation on medicinal plant resources of Glycyrrhiza
uralensis in China and chemical assessment of its underground part. J Nat Med 63(2):137–146
Hwang IK, Lim SS, Choi KH, Yoo KY, Shin HK, Kim EJ, Yoon-Park JH, Kang TC, Kim YS,
Kwon DY, Kim DW, Moon WK, Won MH (2006) Neuroprotective effects of roasted licorice,
not raw form, on neuronal injury in gerbil hippocampus after transient forebrain ischemia. Acta
Pharmacol Sin 27:959–965
References 65

Iba K, Chiba H, Sawada N, Hirota S, Ishii S, Mori M (1995) Glucocorticoids induce

mineralization coupled with bone protein expression without influence on growth of a human
osteoblastic cell line. Cell Struct Funct 20:319–330
Ii T, Satomi Y, Katoh D, Shimada J, Baba M, Okuyama T, Nishino H, Kitamura N (2004)
Induction of cell cycle arrest and p21(CIP1/WAF1) expression in human lung cancer cells by
isoliquiritigenin. Cancer Lett 207:27–35
Ikeda K (2007) Glycyrrhizin injection therapy prevents hepatocellular carcinogenesis in patients
with interferon-resistant active chronic hepatitis C. Hepatol Res: Official J Jpn Soc Hepatol 37
(Suppl 2):S287–S293
Ikeda K, Arase Y, Kobayashi M, Saitoh S, Someya T, Hosaka T, Sezaki H, Akuta N, Suzuki Y,
Suzuki F, Kumada H (2006) A long-term glycyrrhizin injection therapy reduces hepatocellular
carcinogenesis rate in patients with interferon-resistant active chronic hepatitis C: a cohort
study of 1249 patients. Dig Dis Sci 51:603–609
Isbrucker RA, Burdock GA (2006) Risk and safety assessment on the consumption of Licorice
root (Glycyrrhiza sp.), its extract and powder as a food ingredient, with emphasis on the
pharmacology and toxicology of glycyrrhizin. Regul Toxicol Pharmacol 46(3):167–192
Jang EY, Choe ES, Hwang M, Kim SC, Lee JR, Kim SG, Jeon JP, Buono RJ, Yang CH (2008)
Isoliquiritigenin suppresses cocaine-induced extracellular dopamine release in rat brain through
GABA(B) receptor. Eur J Pharmacol 587:124–128
Jang EY, Hwang M, Yoon SS, Lee JR, Kim KJ, Kim HC, Yang CH (2011) Liquiritigenin
decreases selective molecular and behavioral effects of cocaine in rodents. Curr
Neuropharmacol 9:30–34
Jayaprakasam B, Doddaga S, Wang R, Holmes D, Goldfarb J, Li XM (2009) Licorice flavonoids
inhibit eotaxin-1 secretion by human fetal lung fibroblasts in vitro. J Agric Food Chem 57:
820–825
Jirawattanapong W, Saifah E, Patarapanich C (2009) Synthesis of glabridin derivatives as
tyrosinase inhibitors. Arch Pharm Res 32:647–654
Jungbauer A, Medjakovic S (2014) Phytoestrogens and the metabolic syndrome. J Steroid
Biochem Mol Biol 139:277–289
Jutooru I, Chadalapaka G, Chintharlapalli S, Papineni S, Safe S (2009) Induction of apoptosis and
nonsteroidal anti-inflammatory drugactivated gene 1 in pancreatic cancer cells by a
glycyrrhetinic acid derivative. Mol Carcinog 48:692–702
Kajiyama K, Demizu S, Hiraga Y, Kinoshita K, Koyama K, Takahashi K, Tamura Y, Okada K,
Kinoshita T (1992) New prenylflavones and dibenzoylmethane from Glycyrrhiza inflata. J Nat
Prod 55(9):1197–1203
Kakegawa H, Matsumoto H, Satoh T (1992) Inhibitory effects of some natural products on the
activation of hyaluronidase and their anti-allergic actions. Chem Pharm Bull 40:1439–1442
Kamei J, Nakamura R, Ichiki H, Kubo M (2003) Antitussive principles of Glycyrrhizae radix, a
main component of the Kampo preparations Bakumondo-to (Mai-men-dong-tang). Eur J
Pharmacol 469:159–163
Kamei J, Saitoh A, Asano T, Nakamura R, Ichiki H, Iiduka A, Kubo M (2005) Pharmacokinetic
and pharmacodynamic profiles of the antitussive principles of Glycyrrhizae radix (licorice), a
main component of the Kampo preparation Bakumondo-to (Mai-men-dong-tang). Eur J
Pharmacol 507:163–168
Kanazawa M, Satomi Y, Mizutani Y, Ukimura O, Kawauchi A, Sakai T, Baba M, Okuyama T,
Nishino H, Miki T (2003) Isoliquiritigenin inhibits the growth of prostate cancer. Eur Urol
43:580–586
Kang JS, Yoon YD, Cho IJ, Han MH, Lee CW, Park SK, Kim HM (2005) Glabridin, an isoflavan
from licorice root, inhibits inducible nitric-oxide synthase expression and improves survival of
mice in experimental model of septic shock. J Pharmacol Exp Ther 312:1187–1194
Kang HE, Kim YW, Sohn SI, Baek SR, Lee JW, Kim SG, Lee I, Lee MG (2010a)
Pharmacokinetics of liquiritigenin and its two glucuronides, M1 and M2, in rats with acute
hepatitis induced by dgalactosamine/lipopolysaccharide or CCl(4). Xenobiotica 40:424–436
Kang HE, Chung HJ, Kim HS, Lee JW, Lee MG (2010b) Pharmacokinetic interaction between
liquiritigenin (LQ) and DDB: increased glucuronidation of LQ in the liver possibly due to
increased hepatic blood flow rate by DDB. Eur J Pharm Sci 39:181–189
66 7 Pharmacological Activities and Phytochemical Constituents

Kao TC, Shyu MH, Yen GC (2009) Neuroprotective effects of glycyrrhizic acid and
18beta-glycyrrhetinic acid in PC12 cells via modulation of the PI3K/Akt pathway. J Agric
Food Chem 57:754–761
Kao TC, Shyu MH, Yen GC (2010) Glycyrrhizic acid and 18betaglycyrrhetinic acid inhibit
inflammation via PI3K/Akt/GSK3beta signaling and glucocorticoid receptor activation. J Agric
Food Chem 58:8623–8629
Kao TC, Wu CH, Yen GC (2013) Glycyrrhizic acid and 18betaglycyrrhetinic acid recover
glucocorticoid resistance via PI3K-induced AP1, CRE and NFAT activation. Phytomedicine
20:295–302
Kao T-C, Wu C-H, Yen G-C (2014) Bioactivity and potential health benefits of licorice. J Agric
Food Chem 62:542–553
Kar A (2007) Pharmaocgnosy and pharmacobiotechnology. New Age International Ltd.
Publishers, New Delhi, pp 332–600
Khalaf I, Vlase L, Lazăr D, Corciovă A, Ivãnescu B, Lazăr MI (2010) Hplc-Ms study of
phytoestrogens from Glycyrrhiza glabra. Farmacia 58(1):89–94
Kim DH, Lee SW, Han MJ (1999) Biotransformation of glycyrrhizin to 18beta-glycyrrhetinic
acid-3-O-beta-D-glucuronide by Streptococcus LJ-22, a human intestinal bacterium. Biol
Pharm Bull 22:320–322
Kim SC, Byun SH, Yang CH, Kim CY, Kim JW, Kim SG (2004) Cytoprotective effects of
Glycyrrhizae radix extract and its active component liquiritigenin against cadmium-induced
toxicity (effects on bad translocation and cytochrome c-mediated PARP cleavage). Toxicology
197:239–251
Kim YW, Ki SH, Lee JR, Lee SJ, Kim CW, Kim SC, Kim SG (2006) Liquiritigenin, an aglycone
of liquiritin in Glycyrrhizae radix, prevents acute liver injuries in rats induced by
acetaminophen with or without buthionine sulfoximine. Chem Biol Interact 161:125–138
Kim YW, Zhao RJ, Park SJ, Lee JR, Cho IJ, Yang CH, Kim SG, Kim SC (2008) Anti-inflammatory
effects of liquiritigenin as a consequence of the inhibition of NF-kappaB-dependent iNOS and
proinflammatory cytokines production. Br J Pharmacol 154:165–173
Kim YW, Kang HE, Lee MG, Hwang SJ, Kim SC, Lee CH, Kim SG (2009) Liquiritigenin, a
flavonoid aglycone from licorice, has a choleretic effect and the ability to induce hepatic
transporters and phase-II enzymes. Am J Physiol Gastrointest Liver Physiol 296:G372–G381
Kim KR, Jeong CK, Park KK, Choi JH, Park JH, Lim SS, Chung WY (2010) Anti-inflammatory
effects of licorice and roasted licorice extracts on TPA-induced acute inflammation and
collageninduced arthritis in mice. J Biomed Biotechnol 709378
Kim HJ, Seo JY, Suh HJ, Lim SS, Kim JS (2012a) Antioxidant activities of licorice-derived
prenylflavonoids. Nutr Res Pract 6:491–498
Kim HJ, Lim SS, Park IS, Lim JS, Seo JY, Kim JS (2012b) Neuroprotective effects of
dehydroglyasperin C through activation of heme oxygenase-1 in mouse hippocampal cells.
J Agric Food Chem 60:5583–5589
Kim ME, Kim HK, Kim DH, Yoon JH, Lee JS (2013) 18beta-Glycyrrhetinic acid from licorice
root impairs dendritic cells maturation and Th1 immune responses. Immunopharmacol
Immunotoxicol 35:329–335
Kinoshita T, Tamura Y, Mizutani K (2005) The isolation and structure elucidation of minor
isoflavonoids from licorice of Glycyrrhiza glabra origin. Chem Pharm Bull 53:847–849
Kobayashi S, Miyamoto T, Kimura I, Kimura M (1995) Inhibitory effect of isoliquiritin, a
compound in licorice root, on angiogenesis in vivo and tube formation in vitro. Biol Pharm
Bull 18:1382–1386
Kong LD, Zhang Y, Pan X, Tan RX, Cheng CH (2000) Inhibition of xanthine oxidase by
liquiritigenin and isoliquiritigenin isolated from Sinofranchetia chinensis. Cell Mol Life Sci
57:500–505
Krausse R, Bielenberg J, Blaschek W, Ullmann U (2004) In vitro anti-Helicobacter pylori activity
of extractum liquiritiae, glycyrrhizin and its metabolites. J Antimicrob Chemother 54:243–246
Kroes BH, Beukelman CJ, van den Berg AJ, Wolbink GJ, van Dijk H, Labadie RP (1997)
Inhibition of human complement by beta-glycyrrhetinic acid. Immunology 90(1):115–120
Kumagai A, Nishino K, Shimomura A, Kin T, Yamamura Y (1967) Effect of glycyrrhizin on
estrogen action. Endocrinol Japon 14:34–38
References 67

Kuwajima H, Taneda Y, Chen WZ, Kawanishi T, Hori K, Taniyama T, Kobayashi M, Ren J,

Kitagawa I (1999) Variation of chemical constituents in processed licorice roots: quantitative
determination of saponin and flavonoid constituents in bark removed and roasted licorice roots.
Yakugaku Zasshi 119:945–955
Lampi G, Deidda D, Pinza M, Pompei R (2001) Enhancement of anti-herpetic activity of
glycyrrhizic acid by physiological proteins. Antiviral Chem Chemother 12:125–131
Lee CS, Kim YJ, Lee MS, Han ES, Lee SJ (2008) 8beta-Glycyrrhetinic acid induces apoptotic cell
death in SiHa cells and exhibits a synergistic effect against antibiotic anti-cancer drug toxicity.
Life Sci 83:481–489
Lee JY, Lee JH, Park JH, Kim SY, Choi JY, Lee SH, Kim YS, Kang SS, Jang EC, Han Y (2009)
Liquiritigenin, a licorice flavonoid, helpsmice resist disseminated candidiasis due to Candida
albicans by Th1 immune response, whereas liquiritin, its glycoside form, does not. Int
Immunopharmacol 9:632–638
Lee CS, Yang JC, Kim YJ, Jang ER, Kim W, Myung SC (2010a) 18beta-Glycyrrhetinic acid
potentiates apoptotic effect of trichostatin A on human epithelial ovarian carcinoma cell lines.
Eur J Pharmacol 649:354–361
Lee YS, Kim SH, Kim JK, Shin HK, Kang YH, Park JH, Lim SS (2010b) Rapid identification and
preparative isolation of antioxidant components in licorice. J Sep Sci 33:664–671
Lee YS, Kim SH, Jung SH, Kim JK, Pan CH, Lim SS (2010c) Aldose reductase inhibitory
compounds from Glycyrrhiza uralensis. Biol Pharm Bull 33:917–921
Lee JW, Choe SS, Jang H, Kim J, Jeong HW, Jo H, Jeong KH, Tadi S, Park MG, Kwak TH, Man
Kim J, Hyun DH, Kim JB (2012) AMPK activation with glabridin ameliorates adiposity and
lipid dysregulation in obesity. J Lipid Res 53:1277–1286
Lee KK, Omiya Y, Yuzurihara M, Kase Y, Kobayashi H (2013) Antispasmodic effect of
shakuyakukanzoto extract on experimental muscle cramps in vivo: role of the active
constituents of Glycyrrhizae radix. J Ethnopharmacol 145:286–293
Lennon GG, Lennard M (1964) Today’s drugs. Carbenoxolone sodium. Br Med J 1:1690–1691
Leyden JJ, Shergill B, Micali G, Downie J, Wallo W (2011) Natural options for the management
of hyperpigmentation. J Eur Acad Dermatol Venereol 25:1140–1145
Li S (2003) Compendium of materia medica. Foreign Languages Press, Beijing
Li W, Asada Y, Yoshikawa T (2000) Flavonoid constituents from Glycyrrhiza glabra hairy root
cultures. Phytochemistry 55:447–456
Li JR, Wang YQ, Deng ZZ (2005) Two new compounds from Glycyrrhiza glabra. J Asian Nat
Prod Res 7:677–680
Li K, Ji S, Song W, Kuang Y, Lin Y, Tang S, Cui Z, Qiao X, Yu S, Ye M (2017) Glycybridins A–
K, bioactive phenolic compounds from Glycyrrhiza glabra. J Nat Prod 80(2):334–346
Lin JC (2003) Mechanism of action of glycyrrhizic acid in inhibition of Epstein-Barr virus
replication in vitro. Antiviral Res 59:41–47
Lin KW, Huang AM, Hour TC, Yang SC, Pu YS, Lin CN (2011) 18beta-Glycyrrhetinic acid
derivatives induced mitochondrialmediated apoptosis through reactive oxygen
species-mediated p53 activation in NTUB1 cells. Bioorg Med Chem 19:4274–4285
Lin Y, Kuang Y, Li K, Wang S, Song W, Qiao X, Sabir G, Ye M (2017) Screening for bioactive
natural products from a 67-compound library of Glycyrrhiza inflata. Bioorg Med Chem 25
(14):3706–3713
Liu RT, Zou LB, Lu QJ (2009) Liquiritigenin inhibits Abeta(25–35)-induced neurotoxicity and
secretion of Abeta(1–40) in rat hippocampal neurons. Acta Pharmacol Sin 30:899–906
Liu RT, Zou LB, Fu JY, Lu QJ (2010) Effects of liquiritigenin treatment on the learning and
memory deficits induced by amyloid betapeptide (25–35) in rats. Behav Brain Res 210:24–31
Liu C, Wang Y, Xie S, Zhou Y, Ren X, Li X, Cai Y (2011) Liquiritigenin induces
mitochondria-mediated apoptosis via cytochrome c release and caspases activation in HeLa
cells. Phytother Res 25:277–283
Liu Y, Xie S, Wang Y, Luo K, Wang Y, Cai Y (2012) Liquiritigenin inhibits tumor growth and
vascularization in a Mouse model of HeLa cells. Molecules 17:7206–7216
Lou ZC, Qin B (1995) Species systematization and quality evaluation of commonly used Chinese
traditional drugs, North-Edition vol 1–3. Beijing Medical University Press and Peking Union
Medical College Press, Beijing, p 19
68 7 Pharmacological Activities and Phytochemical Constituents

Ma J, Fu NY, Pang DB, Wu WY, Xu AL (2001) Apoptosis induced by isoliquiritigenin in human

gastric cancer MGC-803 cells. Planta Med 67:754–757
Ma CJ, Li GS, Zhang DL, Liu K, Fan X (2005) One step isolation and purification of liquiritigenin
and isoliquiritigenin from Glycyrrhiza uralensis Risch. using high-speed counter-current
chromatography. J Chromatogr 1078:188–192
Ma X, Lian QQ, Dong Q, Ge RS (2011) Environmental inhibitors of 11beta-hydroxysteroid
dehydrogenase type 2. Toxicology 285:83–89
Madziga HA, Sanni S, Sandabe UK (2010) Phytochemical and elemental analysis of Acalypha
wilkesiana leaf. J Am Sci 6(11):510–514
Mae T, Kishida H, Nishiyama T, Tsukagawa M, Konishi E, Kuroda M, Mimaki Y, Sashida Y,
Takahashi K, Kawada T, Nakagawa K, Kitahara M (2003) A licorice ethanolic extract with
peroxisome proliferator-activated receptor-gamma ligand-binding activity affects diabetes in
KK-Ay mice, abdominal obesity in diet-induced obese C57BL mice and hypertension in
spontaneously hypertensive rats. J Nutr 133:3369–3377
Maggiolini M, Statti G, Vivacqua A, Gabriele S, Rago V, Loizzo M, Menichini F, Amdo S (2002)
Estrogenic and antiproliferative activities of isoliquiritigenin in MCF7 breast cancer cells.
J Steroid Biochem Mol Biol 82:315–322
Manfredi KP, Vallurupalli V, Demidova M, Kindscher K, Pannell LK (2001) Isolation of an
anti-HIV diprenylated bibenzyl from Glycyrrhiza lepidota. Phytochemistry 58:153–157
Manns MP, Wedemeyer H, Singer A, Khomutjanskaja N, Dienes HP, Roskams T, Goldin R,
Hehnke U, Inoue H, European SSG (2012) Glycyrrhizin in patients who failed previous
interferon alpha-based therapies: biochemical and histological effects after 52 weeks. J Viral
Hepatitis 19:537–546
Martinez MJA, Lazaro RM, del Olmo LMB, Benito PB (2008) Anti-infectious activity in the
Anthemideae tribe. Stud Nat Prod Chem 35:445–516
Maurya R, Singh G, Yadav PP (2008) Antiosteoporotic agents from natural sources. Stud Nat Prod
Chem 35:517–545
Mersereau JE, Levy N, Staub RE, Baggett S, Zogovic T, Chow S, Ricke WA, Tagliaferri M,
Cohen I, Bjeldanes LF, Leitman DC (2008) Liquiritigenin is a plant-derived highly selective
estrogen receptor beta agonist. Mol Cell Endocrinol 283:49–57
Messier C, Epifano F, Genovese S, Grenier D (2012) Licorice and its potential beneficial effects in
common oro-dental diseases. Oral Dis 18:32–39
Michaelis M, Geiler J, Naczk P, Sithisarn P, Leutz A, Doerr HW, Cinatl J Jr (2011) Glycyrrhizin
exerts antioxidative effects in H5N1 influenza A virus-infected cells and inhibits virus
replication and proinflammatory gene expression. PLoS ONE 6:e19705
Mitscher LA, Park YH, Clark D, Beal JL (1980) Antimicrobial agents from higher plants.
Antimicrobial isoflavanoids and related substances from Glycyrrhiza glabra L. var. typica.
J Nat Prod 43:259–269
Mollica L, De Marchis F, Spitaleri A, Dallacosta C, Pennacchini D, Zamai M, Agresti A,
Trisciuoglio L, Musco G, Bianchi ME (2007) Glycyrrhizin binds to high-mobility group box 1
protein and inhibits its cytokine activities. Chem Biol 14:431–441
Moro T, Shimoyama Y, Kushida M, Hong YY, Nakao S, Higashiyama R, Sugioka Y, Inoue H,
Okazaki I, Inagaki Y (2008) Glycyrrhizin and its metabolite inhibit Smad3-mediated type I
collagen gene transcription and suppress experimental murine liver fibrosis. Life Sci 83:531–
539
Näf R, Jaquier A (2006) New lactones in licorice (Glycyrhiza glabra L.). Flavor Fragrance J
21:193–197
Nafisi S, Bonsaii M, Manouchehri F, Abdi K (2012a) Interaction of glycyrrhizin and glycyrrhetinic
acid with DNA. DNA Cell Biol 31:114–121
Nafisi S, Manouchehri F, Bonsaii M (2012b) Study on the interaction of glycyrrhizin and
glycyrrhetinic acid with RNA. J Photochem Photobiol, B 111:27–34
Nakagawa K, Kishida H, Arai N, Nishiyama T, Mae T (2004) Licorice flavonoids suppress
abdominal fat accumulation and increase in blood glucose level in obese diabetic KK-A(y)
mice. Biol Pharm Bull 27:1775–1778
Nomura T, Fukai T (1998) Phenolic constituents of licorice (Glycyrrhiza species). In: Herz W et al
(eds) Progress in the chemistry of organic natural products, vol 73. Springer Wien-New York,
pp 1–140
References 69

Nomura T, Fukai T, Akiyama T (2002) Chemistry of phenolic compounds of licorice (Glycyrrhiza

species) and their estrogenic and cytotoxic activities. Pure Appl Chem 74:1199–1206
Numazaki K, Nagata N, Sato T, Chiba S (1994) Effect of glycyrrhizin, cyclosporin A, and tumor
necrosis factor alpha on infection of U-937 and MRC-5 cells by human cytomegalovirus.
J Leukoc Biol 55:24–28
Ogiku M, Kono H, Hara M, Tsuchiya M, Fuji H (2011) Glycyrrhizin prevents liver injury by
inhibition of high-mobility group box 1 production by Kupffer cells after ischemia-reperfusion
in rats. J Pharmacol Exp Ther 339:93–98
Okada K, Tamura Y, Yamamoto M, Inoue Y, Takagaki R, Takahashi K, Demizu S, Kajiyama K,
Hiraga Y, Kinoshita T (1989) Identification of antimicrobial and antioxidant constituents from
licorice of Russian and Xinjiang origin. Chem Pharm Bull (Tokyo) 37:2528–2530
Orlent H, Hansen BE, Willems M, Brouwer JT, Huber R, Kullak-Ublick GA, Gerken G,
Zeuzem S, Nevens F, Tielemans WC, Zondervan PE, Lagging M, Westin J, Schalm SW (2006)
Biochemical and histological effects of 26 weeks of glycyrrhizin treatment in chronic hepatitis
C: a randomized phase II trial. J Hepatol 45:539–546
Ozog MA, Siushansian R, Naus CC (2002) Blocked gap junctional coupling increases
glutamate-induced neurotoxicity in neuron-astrocyte co-cultures. J Neuropathol Exp Neurol
61:132–141
Pan X, Kong LD, Zhang Y, Cheng CH, Tan RX (2000) In vitro inhibition of rat monoamine
oxidase by liquiritigenin and isoliquiritigenin isolated from Sinofranchetia chinensis. Acta
Pharmacol Sin 21:949–953
Paolini M, Barillari J et al (1999) Effect of liquorice and glycyrrhizin on rat liver carcinogen
metabolizing enzymes. Cancer Lett 145:35–42
Parvaiz M, Hussain K, Khalid S, Hussnain N, Iram N, Hussain Z, Ali MA (2014) A review:
medicinal importance of Glycyrrhiza glabra L. (Fabaceae Family). Global J Pharmocol 8(1):
8–13
Patil SM, Patil MB, Sapkale GN (2009) Antimicrobial activity of Glycyrrhiza glabra Linn. roots.
Int J Chem Sci 7(1):585–591
Ploeger B, Mensinga T, Sips A, Seinen W, Meulenbelt J, DeJongh J (2001) The pharmacokinetics
of glycyrrhizic acid evaluated by physiologically based pharmacokinetic modeling. Drug
Metab Rev 33:125–147
Pompei R, Flore O, Marccialis MA, Pani A, Loddo B (1979) Glycyrrhizic acid inhibits virus
growth and inactivates virus particles. Nature 281:689–690
Porter SR, Scully Cbe C (2007) Aphthous ulcers (recurrent). Clin Evid (Online) 1303
Qiao X, Liu CF, Ji S, Lin XH, Guo DA, Ye M (2014) Simultaneous determination of five minor
coumarins and flavonoids in Glycyrrhiza uralensis by solid-phase extraction and
high-performance liquid chromatography/electrospray ionization tandem mass spectrometry.
Planta Med 80(2–3):237–242
Ram A, Mabalirajan U, Das M, Bhattacharya I, Dinda AK, Gangal SV, Ghosh B (2006)
Glycyrrhizin alleviates experimental allergic asthma in mice. Int Immunopharm 6(9):1468–1477
Ramli ES, Suhaimi F, Asri SF, Ahmad F, Soelaiman IN (2013) Glycyrrhizic acid (GCA) as
11beta-hydroxysteroid dehydrogenase inhibitor exerts protective effect against
glucocorticoid-induced osteoporosis. J Bone Miner Metab 31:262–273
Rhee SD, Kim CH, Park JS, Jung WH, Park SB, Kim HY, Bae GH, Kim TJ, Kim KY (2012)
Carbenoxolone prevents the development of fatty liver in C57BL/6-Lep ob/ob mice via the
inhibition of sterol regulatory element binding protein-1c activity and apoptosis. Eur J
Pharmacol 691:9–18
Rizzato G, Scalabrin E, Radaelli M, Capodaglio G, Piccolo O (2017) A new exploration of licorice
metabolome. Food Chem 221:959–968
Sandeep TC, Yau JL, MacLullich AM, Noble J, Deary IJ, Walker BR, Seckl JR (2004)
11Beta-hydroxysteroid dehydrogenase inhibition improves cognitive function in healthy
elderly men and type 2 diabetics. Proc Natl Acad Sci USA 101:6734–6739
Sarker SD, Nahar L (2007) Chemistry for pharmacy students: general, organic and natural product
chemistry. Wiley, London
70 7 Pharmacological Activities and Phytochemical Constituents

Satomi Y, Nishino H, Shibata S (2005) Glycyrrhetinic acid and related compounds induce G1 arrest
and apoptosis in human hepatocellular carcinoma HepG2. Anticancer Res 25(6):4043–4047
Seo JY, Lee YS, Kim HJ, Lim SS, Lim JS, Lee IA, Lee CH, Yoon Park JH, Kim JS (2010)
Dehydroglyasperin C isolated from licorice caused Nrf2-mediated induction of detoxifying
enzymes. J Agric Food Chem 58:1603–1608
Sharma V, Agrawal RC (2013) Glycyrrhiza glabra—a plant for the future. Mintage J Pharm Med
Sci 2(3):15–20
Sharma G, Kar S, Palit S, Das PK (2012) 18beta-glycyrrhetinic acid induces apoptosis through
modulation of Akt/FOXO3a/Bim pathway in human breast cancer MCF-7 cells. J Cell Physiol
227:1923–1931
Shetty AV, Thirugnanam S, Dakshinamoorthy G, Samykutty A, Zheng G, Chen A, Bosland MC,
Kajdacsy-Balla A, Gnanasekar M (2011) 18alpha-glycyrrhetinic acid targets prostate cancer
cells by down-regulating inflammation-related genes. Int J Oncol 39:635–640
Simmler C, Pauli GF, Chen SN (2013) Phytochemistry and biological properties of glabridin.
Fitoterapia 90:160–184
Sitohy MZ, El-Massry RA, El-Saadany SS, Labib SM (1991) Metabolic effect of licorice roots
(Glycyrrhiza glabra) on lipid distribution pattern, liver and renal functions of albino rats.
Nahrung 35:799–806
Sofia H, Walter TM (2009) Review of Glycyrrhiza glabra Linn. Siddha Pap, Med J 2(1):1–7
Somjen D, Katzburg S, Vaya J, Kaye AM, Hendel D, Posner GH, Tamir S (2004) Estrogenic
activity of glabridin and glabrene from licorice roots on human osteoblasts and prepubertal rat
skeletal tissues. J Steroid Biochem Mol Biol 91:241–246
Song D, Gao Y, Wang R, Liu D, Zhao L, Jing Y (2010) Downregulation of c-FLIP, XIAP and
Mcl-1 protein as well as depletion of reduced glutathione contribute to the apoptosis induction
of glycyrrhetinic acid derivatives in leukemia cells. Cancer Biol Ther 9:96–108
Spataro LE, Sloane EM, Milligan ED, Wieseler-Frank J, Schoeniger D, Jekich BM,
Barrientos RM, Maier SF, Watkins LR (2004) Spinal gap junctions: potential involvement
in pain facilitation. J Pain 5:392–405
Stoletov K, Strnadel J, Zardouzian E, Momiyama M, Park FD, Kelber JA, Pizzo DP, Hoffman R,
VandenBerg SR, Klemke RL (2013) Role of connexins in metastatic breast cancer and
melanoma brain colonization. J Cell Sci 126:904–913
Sultana S, Haque A, Hamid K et al (2010) Antimicrobial, cytotoxic and antioxidant activity of
methanolic extract of Glycyrrhiza glabra. Agr Bio J N Am 1(5):957–960
Sun YX, Tang Y, Wu AL, Liu T, Dai XL, Zheng QS, Wang ZB (2010) Neuroprotective effect of
liquiritin against focal cerebral ischemia/reperfusion in mice via its antioxidant and
antiapoptosis properties. J Asian Nat Prod Res 12:1051–1060
Sung MW, Li PC (2004) Chemical analysis of raw, dry-roasted, and honey-roasted licorice by
capillary electrophoresis. Electrophoresis 25:3434–3440
Szpak K, Wybieralska E, Niedzialkowska E, Rak M, Bechyne I, Michalik M, Madeja Z, Czyz J
(2011) DU-145 prostate carcinoma cells that selectively transmigrate narrow obstacles express
elevated levels of Cx43. Cell Mol Biol Lett 16:625–637
Tabuchi M, Imamura S, Kawakami Z, Ikarashi Y, Kase Y (2012) The blood-brain barrier
permeability of 18beta-glycyrrhetinic acid, a major metabolite of glycyrrhizin in Glycyrrhiza
root, a constituent of the traditional Japanese medicine yokukansan. Cell Mol Neurobiol
32:1139–1146
Takahara T, Watanabe A, Shiraki K (1994) Effects of glycyrrhizin on hepatitis B surface antigen: a
biochemical and morphological study. J Hepatol 21:601–609
Takahashi T, Takasuka N, Iigo M, Baba M, Nishino H, Tsuda H, Okuyama T (2004)
Isoliquiritigenin, a flavonoid from licorice, reduces prostaglandin E2 and nitric oxide, causes
apoptosis, and suppresses aberrant crypt foci development. Cancer Sci 95:448–453
Takeda H, Sadakane C, Hattori T, Katsurada T, Ohkawara T, Nagai K, Asaka M (2008)
Rikkunshito, an herbal medicine, suppresses cisplatin-induced anorexia in rats via 5-HT2
receptor antagonism. Gastroenterology 134:2004–2013
References 71

Tanaka S, Sakata Y, Morimoto K, Tambe Y, Watanabe Y, Honda G, Tabata M, Oshima T,

Masuda T, Umezawa T, Shimada M, Nagakura N, Kamisako W, Kashiwada Y, Ikeshiro Y
(2001) Influence of natural and synthetic compounds on cell surface expression of cell
adhesion molecules, ICAM-1 and VCAM-1. Planta Med 67:108–113
Tang W, Eisenbrand G (1992) Chinese drugs of plant origin. Springer, Berlin, pp 567–588
Tawata M, Aida K, Noguchi T, Ozaki Y, Kume S, Sasaki H, Chin M, Onaya T (1992)
Anti-platelet action of isoliquiritigenin, an aldose reductase inhibitor in licorice. Eur J
Pharmacol 212:87–92
Toshio F, Kazue S, Taro N (2003) Preliminary evaluation of anti nephritis and radical scavenging
activities of glabridin from Glycyrrhiza glabra Linn. Fitotherapia 74:624–629
Tsai YM, Yang CJ, Hsu YL, Wu LY, Tsai YC, Hung JY, Lien CT, Huang MS, Kuo PL (2011)
Glabridin inhibits migration, invasion, and angiogenesis of human non-small cell lung cancer
A549 cells by inhibiting the FAK/rho signaling pathway. Integr Cancer Ther 10:341–349
Uto T, Morinaga O, Tanaka H, Shoyama Y (2012) Analysis of the synergistic effect of
glycyrrhizin and other constituents in licorice extract on lipopolysaccharide-induced nitric
oxide production using knock-out extract. Biochem Biophys Res Commun 417:473–478
Varsha S, Agrawal RC, Sonam P (2013) Phytochemical screening and determination of
anti-bacterial and anti-oxidant potential of Glycyrrhiza glabra root extracts. J Environ Res Dev
7(4):1552–1558
Vashist H, Sharma D (2013) Pharmacognostical aspects of Glycyrrhiza glabra. Asian J Pharm
Clin Res 6(4):55–59
Vaya J, Belinky PA, Aviram M (1998) Structural aspects of the inhibitory effect of glabridin on
LDL oxidation. Free Rad Biol Med 24:1419–1429
Vivekanand JHA (2010) Herbal medicines and chronic kidney disease. Nephro 15(2):10–17
Wagner J, Granvogl M, Schieberle P (2016) Characterization of the key aroma compounds in raw
licorice (Glycyrrhiza glabra L.) by means of molecular sensory science. J Agric Food Chem
64:8388–8396
Wang X, Sun H, Zhang A, Sun W, Wang P, Wang Z (2011) Potential role of metabolomics
apporoaches in the area of traditional Chinese medicine: as pillars of the bridge between
Chinese and Western medicine. J Pharm Biomed Anal 55(5):859–868
Wang YG, Zhou JM, Ma ZC, Li H, Liang QD, Tan HL, Xiao CR, Zhang BL, Gao Y (2012)
Pregnane X receptor mediated-transcription regulation of CYP3A by glycyrrhizin: a possible
mechanism for its hepatoprotective property against lithocholic acid-induced injury. Chem Biol
Interact 200:11–20
Watjen W, Weber N, Lou YJ, Wang ZQ, Chovolou Y, Kampkotter A, Kahl R, Proksch P (2007)
Prenylation enhances cytotoxicity of apigenin and liquiritigenin in rat H4IIE hepatoma and C6
glioma cells. Food Chem Toxicol 45:119–124
Wegener JW, Nawrath H (1997) Cardiac effects of isoliquiritigenin. Eur J Pharmacol 326:37–44
Whorwood CB, Sheppard MC, Stewart PM (1993) Licorice inhibits 11 beta-hydroxysteroid
dehydrogenase messenger ribonucleic acid levels and potentiates glucocorticoid hormone
action. Endocrinology 132:2287–2292
Williamson EM (2003) Licorice. In: Potter’s cyclopedia of herbal medicines. C.W. Daniels,
Saffron Walden, pp 269–271
Won SR, Kim SK, Kim YM, Lee PH, Ryu JH, Kim JW, Rhee HI (2007) Licochalcone A: a lipase
inhibitor from the roots of Glycyrrhiza uralensis. Food Res Int 40:1046–1050
Wu YT, Shen C, Yin J, Yu JP, Meng Q (2006) Azathioprine hepatotoxicity and the protective
effect of liquorice and glycyrrhizic acid. Phytother Res 20(8):640–645
Xie SR, Wang Y, Liu CW, Luo K, Cai YQ (2012) Liquiritigenin inhibits serum-induced
HIF-1alpha and VEGF expression via the AKT/mTOR-p70S6K signalling pathway in HeLa
cells. Phytother Res 26:1133–1141
Xing GX, Li N, Wang T, Yang MY (2003) Advances in studies on flavonoids of licorice. China J
Chin Mater Med 28(7):593–597
Yamamoto S, Aizu E, Jiang H, Nakadate T, Kiyoto I, Wang JC, Kato R (1991) The potent
anti-tumor-promoting agent isoliquiritigenin. Carcinogenesis 12:317–323
72 7 Pharmacological Activities and Phytochemical Constituents

Yamamura Y, Kawakami J, Santa T et al (1992) Pharmacokinetic profile of glycerrhizin in healthy

volunteers by a new high-performance liquid chromatographic method. J Pharm Sci 81:
1042–1046
Yamazaki S, Morita T, Endo H, Hamamoto T, Baba M, Joichi Y, Kaneko S, Okada Y,
Okuyama T, Nishino H, Tokue A (2002) Isoliquiritigenin suppresses pulmonary metastasis of
mouse renal cell carcinoma. Cancer Lett 183:23–30
Yang JC, Myung SC, Kim W, Lee CS (2012) 18betaglycyrrhetinic acid potentiates Hsp90
inhibition-induced apoptosis in human epithelial ovarian carcinoma cells via activation of death
receptor and mitochondrial pathway. Mol Cell Biochem 370:209–219
Yang R, Wang LQ, Yuan BC, Liu Y (2015) The pharmacological activities of licorice. Planta Med
81(18):1654–1669
Ye R, Fan Y-H, Ma C-M (2017) Identification and enrichment of a-glucosidase-inhibiting
dihydrostilbene and flavonoids from Glycyrrhiza uralensis leaves. J Agric Food Chem 65:
510–515
Yehuda I, Madar Z, Szuchman-Sapir A, Tamir S (2011) Glabridin, a phytoestrogen from licorice
root, up-regulates manganese superoxide dismutase, catalase and paraoxonase 2 under glucose
stress. Phytother Res 25:659–667
Yokota T, Nishio H, Kubota Y, Mizoguchi M (1998) The inhibitory effect of glabridin from
licorice extracts on melanogenesis and inflammation. Pigment Cell Res 11:355–361
Yokozawa T, Liu ZW, Chen CP (2000) Protective effects of Glycyrrhizae radix extract and its
compounds in a renal hypoxia (ischemia)-reoxygenation (reperfusion) model. Phytomedicine
6:439–445
Yu XY, Lin SG, Zhou ZW, Chen X, Liang J, Yu XQ, Chowbay B, Wen JY, Duan W, Chan E,
Li XT, Cao J, Li CG, Xue CC, Zhou SF (2007) Role of P-glycoprotein in limiting the brain
penetration of glabridin, an active isoflavan from the root of Glycyrrhiza glabra. Pharm Res
24:1668–1690
Zamansoltani F, Nassiri-Asl M, Sarookhani MR, Jahani-Hashemi H, Zangivand AA (2009)
Antiandrogenic activities of Glycyrrhiza glabra in male rats. Int J Androl 32:417–422
Zani F, Cuzzoni MT, Daglia M, Benvenuti S, Vampa G, Mazza P (1993) Inhibition of
mutagenicity in Salmonella typhimurium by Glycyrrhiza glabra extract, glycyrrhizinic acid,
18a- and 18b-glycyrrhetinic acids. Planta Med 59:502–507
Zhang Q, Ye M (2009) Chemical analysis of the Chinese herbal medicine Gan-Cao (licorice).
J Chromatogr 1216(11):1954–1969
Zhang SP, Zhou YJ, Liu Y, Cai YQ (2009) Effect of liquiritigenin, a flavanone existed from Radix
glycyrrhizae on pro-apoptotic in SMMC-7721 cells. Food Chem Toxicol 47:693–701
Zhang X, Song Y, Han X, Feng L, Wang R, Zhang M, Zhu M, Jia X, Hu S (2013) Liquiritin
attenuates advanced glycation end products-induced endothelial dysfunction via RAGE/
NF-kappaB pathway in human umbilical vein endothelial cells. Mol Cell Biochem 374:
191–201
Zhao Z, Wang W, Guo H, Zhou D (2008) Antidepressant-like effect of liquiritin from Glycyrrhiza
uralensis in chronic variable stress induced depression model rats. Behav Brain Res 194:
108–113
Zhao K, Wang W, Guan C, Cai J, Wang P (2012) Inhibition of gap junction channel attenuates the
migration of breast cancer cells. Mol Biol Rep 39:2607–2613
Zhou L, Tang YP, Gao L, Fan XS, Liu CM, Wu DK (2009) Separation, characterization and
dose-effect relationship of the PPARgamma-activating bio-active constituents in the Chinese
herb formulation ‘San-Ao decoction’. Molecules 14:3942–3951
Zhou M, Higo H, Cai Y (2010) Inhibition of hepatoma 22 tumor by liquiritigenin. Phytother Res
24:827–833
Zhu S, Sugiyama R, Batkhuu J, Sanchir C, Zou K, Komatsu K (2008) Survey of Glycyrrhizae
Radix resources in Mongolia: chemical assessment of the underground part of Glycyrrhiza
uralensis and comparison with Chinese Glycyrrhizea Radix. Phytother Res 22(2):141–148
Chapter 8
Economic Importance

8.1 Traditional Uses

The beneficial effects of liquorice in treating chills, colds, and coughs have been
fully discussed in Ayurveda, as well as in the texts of ancient Egyptians, Greeks,
and Romans. The plant has been prescribed for dropsy during the period of famous
Hippocrates. The reason being that it was quite helpful as thirst-quenching drugs
(Biondi et al. 2005; Mamedov and Egamberdieva 2017). Although the clinical use
of liquorice in modern medicine started around 1930, its effectiveness in the
treatment of stomach and intestinal ulcers has been mentioned in the first century
AD by Pedanios Dioscorides of Anazarba from Adana in present day Turkey, who
is also regarded as the “Father of Pharmacists”. In Ayurveda, people in ancient
Hindu culture have used it for improving sexual vigor. Chinese have been using it
as a tea for strength and endurance (Davis and Morris 1991). The liquorice roots
have been used in the traditional medicine against treating chest and lung diseases,
pneumonia, bronchitis, arthritis, bronchial asthma, kidney diseases, heart diseases,
gastric ulcer, mouth ulcers, coughs, swellings, excessive salivation, fluid retention,
low blood pressure, allergies, catarrhs of the upper respiratory tract, liver toxicity,
hyperglycemia, Addison’s disease, and pancreatic disorders, flatulence, sexual
debility, skin diseases, leucorrhoea, hoarseness, and certain viral infections
(Blumenthal et al. 2000; Anonymous 2005; Armanini et al. 2002; Sharma et al.
2013; Mamedov and Egamberdieva 2017). In Europe, particularly Britain, France,
and Germany, present-day pharmacopeias are in general agreement on the medic-
inal application of this plant. It is used for the treatment of influenza, eye diseases,
uterine complaints, biliousness, liver disease, and arthritis as per the reports pub-
lished on Indian medicine (Saxena 2005; Mamedov and Egamberdieva 2017). The
plant is in use in China since very early times and has been applied to treat acne and
pimples, nervous disorders such as hysteria, irritability, epilepsy, as well as reduce
the toxic or drastic action of other herbs, and to harmonize herbal formulas (Zhu
1998). The studies undertaken by Kong et al. (1984) reveal that liquorice root
extract is used to treat diarrhea in mice, whereas Hong et al. (1988) have demon-
strated its strong diuretic activity in rats. G. glabra extract has also been used to
treat emotional irritability in adults and stress (Tsuda et al. 1986; Shirinyan et al.
1988). The extract has also been used to treat allergic dermatitis and eczema
(Sokolov and Zamotayev 1985; Sheehan and Atherton 1992). According to Yang
et al. (2015), liquorice has been used for the treatment of gastro and respiratory
diseases in traditional treatments as well as for the alleviation of toxicity to other

© The Author(s) 2017 73

M. Öztürk et al., Liquorice, SpringerBriefs in Plant Science,
https://doi.org/10.1007/978-3-319-74240-3_8
74 8 Economic Importance

drugs. In traditional Chinese medicine, it is also honored as the “excellent coor-

dinator” as it harmonizes the activities of other ingredients by promoting their rapid
absorption into the bloodstream, organs, and target cells (Yang et al. 2015).

8.2 Industrial Uses

Liquorice is among the highly significant medicinal plant species in the trade and
business circles of many countries, largely through imports to many countries (Ved
and Goraya 2007; Altay et al. 2016). It continues to be used as a pharmacological
agent as well as an ingredient in tobacco and confectionery throughout the East and
West countries. Studies over the past 50 years have yielded information which has
prompted new interest in the pharmacological and physiological effects of this plant
(Roshan et al. 2012). In 2007, the value of liquorice trade was around 42 million US
$, and evaluation of glycyrrhizin as a natural sweetener has added to its use, and
this is further extended because of its application as a pharmaceutical agent in view
of its anti-inflammatory and hepatoprotective features (Shibata 2000; Parker 2007).
Very extensive studied have been carried out on the chemical constituents of this
plant with regard to isolation of glycyrrhizin as well as many triterpene saponins
and flavonoids (Nomura and Fukai 1998). The cosmetics industry too is using the
flavonoids isolated from liquorice on a large scale. Therefore, liquorice has been
used as a pharmaceutical agent, in cosmetics, as a sweetener, food additive, flavor
additive for tobacco, and in confectionery food (Fig. 8.1).
During 2001–2005, the imports of liquorice roots at the global level have
increased by 3% in value on an average basis. The amount has reached a level of
31.7 million dollars in 2005. On the other hand, the imports of its extracts have
gone up by 5% on yearly basis during 2000–2004, and the amount reported for
2005 is said to lie around 92.3 million dollars. The global import value of its
extracts is three times more than for roots. The reason being former is a processed
value-added product (Stanikzai 2007). Italy and Spain are the main competitors of
this plant in Europe. The manufacturing of its extract is conducted on a wide scale
in Spain, southern France, Sicily, Calabria, Austria, southern Russia, Greece, and
Asia. In Asia, Pakistan, India, China, Iran, and Turkmenistan are the main pro-
ducers of liquorice extracts (Stanikzai 2007). The main producers and exporters of
this plant as underground parts are as follows: Iran, Russia, and China, while the
major exporters of the extract are as follows: USA, France, Italy, Iran, Iraq, Israel,
Japan, and Turkey (Fig. 8.2a–d) as well as China. The main importer of the roots is
America, which is also the main exporter of the extract. Japan is the second largest
importer with about 10,000 tons of roots and 200–250 tons dry extracts per year.
France and Italy are European pioneers in importing liquorice, main sources being
China and Russia. It is worth mentioning here that a small part is used in medicine,
while the major part is used for flavoring (Batanouny et al. 1999). Turkey also
exports liquorice, both as roots and extract. The exported countries are America,
Europe, Africa, Middle East, and some Asian countries (Akan and Balos 2008).
8.2 Industrial Uses 75

1 2 3

4 5 6

7 8 9

10 11 12

13 14 15

16 17 18
 76 8 Economic Importance

JFig. 8.1 Some worldwide industrial uses of liquorice (1 dried root; 2–5 liquorice sherbet; 6–9
liquorice honey; 10, 11 liquorice tea; 12, 13 liquorice candy; 14 Marvis toothpaste; 15, 16
liquorice shampoo; 17, 18 cigarette). Note In this figure, Photo 1–5 www.meyankoku.gen.tr; www.
dunyabulteni.net; www.tr.zuhoo.net; www.haberciniz.biz; www.urfa.com; www.sifamarketim.
com; Photo 6–9 www.sifamarketim.com; Photo 10, 11 www.healthylifestyleshopper.com; Photo
12, 13 www.azimagess.com; Photo 14 www.gottheknack.blogspot.ru; Photo 15, 16 www.lelong.
com.my, www.kozmetikas.blogspot.ru; and Photo 17, 18 www.au.northerner.com; www.katsa-
fados.com

(a) Tonnes
16000 14938
14000
12000 10713 10893
9650
10000
7715 8277 8100
8000 7071 7016
6400 5970 6226
5717 5600
6000 4942 5128
4000
2000
0
1877 1878 1879 1880 1881 1882 1883 1884 1885 1886 1888 1891 1892 1898 1899 1900

Fig. 8.2 Between 1877 and 2004 years, the amount of liquorice roots exported from Turkey
(tons) [İlisulu 1974; İlisulu and Kolsarıcı 1986; Güneş 2004; Akan and Balos 2008; Özgün 2014].
a Liquorice production between 1877 and 1900. b Liquorice production between 1901 and 1927.
c Liquorice production between 1963 and 1978. d Liquorice production between 1980 and 2004

(b)
Tonnes
25000
19795
20000 18467 17692
16788
15507 15314
14047 14333
15000 13034 12071 12035 12937

10000 7747 8387

5000 3525

0
1901 1902 1903 1904 1907 1908 1910 1911 1912 1913 1923 1924 1925 1926 1927

Fig. 8.2 (continued)

This trade has been going on since first days of the establishment of Turkish
Republic, and main exporting area has been Izmir. In 2010 alone, the Turkey has
exported around 300,000 tons liquorice roots with an export value totalling 525
million dollars (Yoğunlu 2011).
8.2 Industrial Uses 77

(c)
Tonnes
6000 5589

5000
4268
4008
4000 3784
3040
3000 2736
2054 1912 1976
2000 1571 1576 1507 1368
1058
1000 565

0
1963 1964 1965 1966 1967 1968 1969 1970 1971 1972 1973 1975 1976 1977 1978

Fig. 8.2 (continued)

(d)
Tonnes
8000 7379
7000
6000 5598
5000 4170
4000 35323274
2856
3000 2148 2125
17451685
2000 1285 1148 10661130
654 514 522
1000 298 549 266 357
0

Fig. 8.2 (continued)

The cultivation areas of this plant in nature extend between Turkey and China
together with Southern European countries (Rauchensteiner et al. 2005; Khalesi
2015). One of the major producers is Chinese who use it as plant medicine with
yearly trading of US 60 billion dollars (Dubey et al. 2008). Although ginseng is the
first herbal medicine in China, liquorice distributed mostly in the northwest of
country holds the second place. The species evaluated are as follows: G. uralensis,
G. inflata, and G. glabra (Chen et al. 2013). China is expected to become a net
importer. Second largest producer on global scale is Iran, where Shiraz, the region
located in the southwest of Iran, is the main manufacturer of Iranian liquorice with
the variety of G. violacca (Ghahraman 1999; Khalesi 2015). Iran has lately faced
severe difficulties in the supply of liquorice to the new customers because of the
economic sanctions by Europe and America (Khalesi 2015). In Europe, the main
producers are listed as follows: the Netherlands, Spain, and Italy, with a total
production of about few hundred tons (Khalesi 2015). The manufacturers of
78 8 Economic Importance

extracts are however, only in China and Iran. The average price for liquorice extract
is estimated to lie around 6 Euro per kg, whereas Chinese liquorice is the most
expensive due to its high Glycyrrhizic acid content (always above 4.0%) (Cirillo
et al. 2011). Main importers of its products on global scale are Japan, Korea,
Germany, the Netherlands, and America (Khalesi 2015).
Commercially, liquorice is added to chewing gum, chocolate candy, cigarettes,
smoking mixtures, chewing tobacco, and snuff as sweetening agents (Tyler et al.
1988; De Klerk et al. 1997). It gives sparkle and aroma to confectionary products
and beer, respectively, and serves as a preservative in food industry. Liquorice is
also frequently employed to mask the taste of bitter drugs such as aloe, quinine, and
others. The surfactant properties of the saponins facilitate the absorption of poorly
absorbed drugs, such as anthraquinone glycosides (Tyler et al. 1988). Some of the
products which have glycyrrhizinic acid are presented in Table 8.1 (De Klerk et al.
1997). In addition to industrial uses of glycyrrhizin, it is included as an adhesive
agent in insecticides as well wetting agent (surfactant). The liquorice extract resi-
dues have been successfully used to extinguish fires in a fire-foam suspension right
from 1906 (Houseman 1944). Similarly, it has been used as an emulsifier in UK, to
create foam in drinks and alcoholic beverages (Lucas 1976; Houseman 1944).
These applications have continued from late 1940s up to 1950s (Roshan et al.
2012). It is also used to insulate fiberboard and serves as a compost for growing
mushrooms and as feed for cattle, horses, and chickens (Armanini et al. 2005;
Isbrucker and Burdock 2006; Timofeyer 1984; Yumatni et al. 1980).
Liquorice is a common and useful ingredient in cosmetic sector. It is used for
depigmentation, as an emollient and soothing agent (Nomura et al. 2002). Modern-day
herbalist Jeanne Rose recommends making a steam facial with liquorice, comfrey,
together with chamomile or lavender. The topical treatment with a gel containing 2%
liquorice extract has successfully lead to significant improvement in erythema, edema,
and pruritus in a clinical study (Saeedi et al. 2003). Its extracts are also used as skin
depigmenting agents and are effective in the treatment of postinflammatory hyper-
pigmentation, in particular the one caused by chemical peeling and laser therapy
(Callender et al. 2011). It helps to open the pores and allows the other cleansing and
healing herbs to penetrate the skin. The use of liquorice root as a shampoo ingredient
has been reported to suppress the secretion of scalp sebum for a week after sham-
pooing, thereby postponing the oily sheen (Fig. 8.1). It is also used in mouthwash and
toothpastes as a sweetening and flavoring agent, sometimes mixed with anise and used
in liqueurs as well as in herbal teas.

Table 8.1 Products containing considerable amounts of glycyrrhizinic acid (De Klerk et al. 1997)
Confectionery Liquorice sticks, bricks, cakes, toffee, pipes, bars, balls, tubes, Catherine
wheels, pastilles and allsorts, Sorbits chewing gum, and Stimorol
chewing gum
Health products Liquorice-flavored diet gum, Throat pearls, Liquorice-flavored cough
mixtures, Herbal cough mixtures, and Liquorice tea
All types of Russian, Iranian, Chinese, Turkish, Afghan and unknown origin
liquorice root chewing tobacco, and alcoholic drinks
8.2 Industrial Uses 79

The liquorice adds flavor, color, and a foamy head when added to the beer and stout
preparations. It can at the same time intensify other flavors. The plant has been
commercially in use for the preparation of pastries, ice creams, puddings, soy sauce,
and soy-based meat substitutes (Rogers 2014). It has been and is used in a number of
foods, mainly condiments and confectionery due to its sweet flavor. The soy sauce and
sweet chili sauce both contain liquorice powder as a condiment which gives unique
sweet flavor, referred to as mellow in English (Kao et al. 2014). In the confectionery
products, flavoring with liquorice plant root extract is a common practice; similarly,
candies like red vines and London drops are also flavored with it. Tobacco manu-
facturers use it in considerable amounts in their products. The block, powder, and
extract of this plant are used in tobacco for multiple purposes (Kao et al. 2014).
According to Carmines et al. (2005), it is added to tobacco to enhance and harmonize
the flavor of smoke, reduce mouth and throat dryness, improve the moisture-holding
feature of tobacco to increase its stability and shelf life, act as a surface-active agent
during the spraying process of the casing ingredients, improve uniformity of the flavor
absorption, and minimize the rough smoke character by balancing the overall flavor
profile of the tobacco smoke. Although excessive consumption is reported to produce
harmful consequences (Rao 1993), it is generally recognized as safe, indicating that it
does not represent a hazard to the public when used properly. Liquorice is reported to
be the common and useful ingredient in cosmetics (Kao et al. 2014). The extract is also
reported to inhibit the rate-limiting first step of the oxidation of tyrosinase (Kim and
Uyama 2005). This brings it to the forefront as an effective treatment for melasma
(Sheth and Pandya 2011). Moreover, the extract is highly useful in the treatment of
aphthous ulcers (Burgess et al. 2008); even its deglycyrrhizinated form (DLG) produces
a positive effect (Das et al. 1989).

8.2.1 Liquorice as an Industrial Resource: A Case Study

from Japan

According to Hayashi and Sudo (2009) for the production of glycyrrhizin, cos-
metics, and food additives, very large quantities of liquorice derived from G. glabra
and G. inflata (Xinjiang-Gancao) are imported by Japan as raw materials.
Dongbei-Gancao (Tohoku-Kanzo in Japanese) and Xibei-Gancao (Seihoku-Kanzo
in Japanese) are also imported from China but are mainly used in the preparation of
Japanese Kampo medicines, mainly derived from G. uralensis.
The trade statistics related to liquorice import in Japan reveal that since it is not
produced locally in Japan, they import it from China, Afghanistan, Turkmenistan,
Uzbekistan, and Pakistan (Hayashi and Sudo 2009). The total amount imported has
been 10,723,342 kg in 1987, but in 2007, it has decreased to 1,377,213 kg. At
present, the major proportion of glycyrrhizin is extracted. Its purification is done in
China and few other countries. In view of this, import for glycyrrhizin production
has decreased in Japan (Hayashi and Sudo 2009). A part of it imported from China
80 8 Economic Importance

is the medicinal liquorice, which is more expensive than the one used for gly-
cyrrhizin production as well as few other products. Some are also imported from
Australia; 144,710 kg of liquorice has been imported from Australia in 2007, which
is quite remarkable. Currently, it is cultivated on a farm owned by a Japanese
glycyrrhizin-manufacturing company, namely, Maruzen Pharmaceuticals Co. Ltd.,
which is used for glycyrrhizin production together with other products (Hayashi and
Sudo 2009).

8.2.1.1 Applications of Liquorice and Its Derivatives in Japan

(Hayashi and Sudo 2009)

Use in the preparation of Kampo medicines

The indispensable ingredient of the traditional Kampo medicines in Japan is
Glycyrrhiza radix (root of liquorice). Out of 210 Kampo prescriptions approved by
the Ministry of Health, Labour and Welfare of Japan, 71% (150 preparations)
contain liquorice. In the Japanese Pharmacopeia, both G. uralensis and G. glabra
are listed, but G. inflata is not in the list. G. uralensis, imported from China, is the
major source of the medicinal liquorice used in Kampo medicines. The standards of
the Japanese Pharmacopeia XV clearly make a mention the amount for use in the
medicinal application of licorice in Kampo medicines; the minimum glycyrrhizin
content in these is mentioned to be only 2.5% (Hayashi and Sudo 2009).
Pharmaceutical preparations
According to Hayashi and Sudo (2009), glycyrrhizin is a prescription drug used in the
treatment of liver and allergic diseases in Japan. It is manufactured as an injectable
preparation (Stronger Neo-Minophagen® C) and in a tablet form (Glycyron®) by a
Japanese company, namely, Minophagen Pharmaceutical Co. Ltd. Stronger
Neo-Minophagen® C has been available in the Japanese market for over 60 years. In
addition, it is available in China, Korea, Taiwan, Indonesia, India, and Mongolia, where
the prevalence of viral hepatitis B and C is relatively high. Glycyrrhizin, glycyrrhetinic
acid, and licorice extracts are used in various over-the-counter drugs, including
anti-allergic and anti-inflammatory drugs. In addition, in England, the glycyrrhetinic
acid derivative glycyrrhetinic acid 3-b-O-hemisuccinate (carbenoxolone) is a pre-
scription drug used in the treatment of peptic ulcers (Hayashi and Sudo 2009).
Cosmetics
Liquorice extracts and many glycyrrhizin derivatives are widely used in the preparation
of cosmetics in Japan. Glycyrrhizin as well as powdered Glycyrrhiza roots, Glycyrrhiza
extracts, glycyrrhetinic acid, stearyl glycyrrhetinate, pyridoxine glycyrrhetinate, and
glycyrrhetinic acid 3-b-O-hemisuccinate (carbenoxolone) are used in cosmetics for
their anti-inflammatory action. Furthermore, glabridin-containing glycyrrhiza flavo-
noids isolated from G. glabra are used in cosmetic preparations owing to their skin
8.2 Industrial Uses 81

whitening, anti-sensitizing, and anti-inflammatory properties (Yokota et al. 1998;

Hayashi and Sudo 2009).

Food additives
Glycyrrhizin imparts a sweet taste to foods; moreover, it has salt-softening and
flavor-enhancing properties and is also heat stable (Hayashi and Sudo 2009). Most
Japanese people do not like the long-lasting sweet taste of glycyrrhizin; however, a
more acceptable sweetness can be created by using a combination of glycyrrhizin
and natural sugars or other sweeteners. Therefore, glycyrrhizin and licorice extracts
are used as food additives in a variety of foods; such as snacks, instant noodles, and
sauces contain licorice extracts. Glycyrrhizin is used in sweet foods such as sweet
snacks, ice creams, and sherbets to enhance their sweetness. It is also used to reduce
the saltiness of salty foods such as soy sauce, other sauces, savory snacks,
Kamaboko (boiled fish paste), Tsukudani (fish boiled in soy sauce), tsukemono
(Japanese pickles), and sausages in Japan (Hayashi and Sudo 2009).
In Japan, enzymatically modified licorice extract (a-glycosyl-glycyrrhizin) and
enzymatically hydrolyzed licorice extract (glycyrrhetinic acid 3-O-glucuronide) are
also used as sweeteners (Hayashi and Sudo 2009). The former is produced by
treating the extract with cyclodextrin glycosyltransferase, and it is used as a
sweetener because of it has higher solubility and better taste than the untreated
licorice extract (Liu et al. 2000). The latter is obtained by enzymatic hydrolyzation
of the licorice extract. The sweetness of this licorice is attributable to glycyrrhetinic
acid 3-O-glucuronide (Kuramoto et al. 1994), which imparts a strong sweetness that
is approximately 941 times that of sucrose (Mizutani et al. 1994).
Flavor additives for tobacco
Large quantities of licorice extracts are used in the tobacco industry (Hayashi and
Sudo 2009). Licorice not only imparts a sweet taste but also an aroma to tobacco,
which makes it mild (Nieman 1957). It also prevents the desiccation of tobacco
(Hayashi and Sudo 2009). The licorice extracts used in the tobacco industry are
supplied by an American company, namely, MAFCO (Hayashi and Sudo 2009).
The liquorice used for this purpose in Japan is imported from countries such as
China and USA in 1987; USA, Israel, China, and India in 2007 (Hayashi and Sudo
2009). The trade statistics related to licorice extracts in Japan in 1987 and 2007.
Japan imported large quantities (848,704 kg in 1987 and 458,179 kg in 2007) of
licorice extracts for tobacco production from the USA, and the value for the same in
2007 was more than 500 million Yen (Hayashi and Sudo 2009).
Confectionery
Liquorice extracts were first used for flavoring confectionery products in England
during the eighteenth century; it was blended with sugar, flour, and other ingredients to
make Pontefract cakes (Nieman 1957). Nowadays, liquorice confectionery is widely
available in Western countries, and large quantities of licorice are used in the con-
fectionery industry. However, since the Japanese do not like the long-lasting sweet taste
of glycyrrhizin, licorice confectionery is not popular in Japan (Hayashi and Sudo 2009).
82 8 Economic Importance

8.3 Other Uses

8.3.1 Liquorice Drinks

In Turkey, Southeastern Anatolia, especially in Adana, Hatay, Sanliurfa,

Diyarbakir, Batman, Mardin, Adıyaman, Siirt, and Gaziantep, an extract obtained
for consuming the liquorice drink is prepared by mixing roots with water. It is used
in abundance in these regions. The fresh roots are carefully washed with water to
remove any adherents and sun-dried. Dried roots are crushed to get fiber-like
product. These fibers are mingled with some carbonate and cinnamon powder
added to give good smell. It is placed in a big wooden bowl with a tap at the bottom
and water added. Water is withdrawn by tap from the wooden bowl taken and
poured again and again over the fiber, till the extract gives desired taste and color.
The extract is taken from the tap and sent for sale (Fig. 8.3) (Akan and Balos 2008).
The two general forms of liquorice are offered in the markets, these are either
roots or the extract. The long brown roots are usually harvested from the field from
3 to 4 years old plants and sun-dried (Cheel et al. 2013). The residual stems and
fibrous roots are separated (Ariño et al. 2007b). The extract is prepared by chopping
roots followed by their steam extraction (Ariño et al. 2007a), and liquor is filtered
and concentrated. The final product may be a solid block or spray-dried powder
(Khalesi 2015).

8.3.2 Meyan Balı (the Succus Liquiritiae)

The sun-dried shrinked liquorice roots are treated with boiling water to get a sweet
and delicious dark colored extract, with slightly bitter taste in some cases. This is
called “liquorice syrup” or “succus liquiritiae”. If this extract is not consumed in
short time, it is degraded and to prevent this from happening the extract is con-
centrated to get a solidified extract, also named as block extract. In succus
liquiritiae, glycyrrhizin content varies between 15 and 25%, and it is sold in the
market as 5–10 kg blocks (Baytop 1952; İlisulu 1974).
The fresh liquorice roots brought to the factory for the production of succus
liquiritiae contain 20–25% water-soluble substance, but the values go up to 30–40%
after drying. The former are sugars, glycyrrhizin, resins (small amount), starch
(small amount), colorant (small amount), and a small amount of other chemical
substances. The remaining pulp is mainly cellulose (Baytop 1952).
The composition of the succus liquiritiae prepared from liquorice roots in the
Aegean region of Turkey is as follows: 14–15.9% water, 5–6.9% ash, 4–6% water
insoluble portion, 3.5–5.2% glucose, 5.8–6.2% sucrose, 10.9–33% gum and starch,
and 23.2–25.4% glycyrrhizin (Baytop 1952; İlisulu 1974; İlisulu and Kolsarıcı
1986).
8.3 Other Uses 83

Fig. 8.3 Liquorice root and drinks seller

Its preparation passes through the following stages:

• Cleaning and washing of roots.
• Extraction with “reverse current” operation in extraction batteries.
• Brewing and reposing.
• Separation of the sweet drink in three-stage evaporators.
• Repose and filter.
• Cake production in moulds.
• Transportation to the packaging hall.
84 8 Economic Importance

8.3.3 Use as Animal Feed

Ozhan and Gol (1975) showed that the leaves of G. glabra can be used to meet the
forage requirements of ruminant animals when quality and quantity of forage is
limited. Although G. glabra is one of the naturally grown plants used to meet
requirements of small ruminants in some semiarid regions of Turkey during the
critical periods of the year there are very few studies available to validate the
nutritional quality of G. glabra leaves (Kamalak 2006).
Kamalak (2006) has studied the nutritive values of G. glabra leaves, hand harvested
at prebud, mid, and late flower stages from three plots. He has evaluated this in terms of
chemical composition, in vitro gas production, and in situ dry matter (DM) and crude
protein (CP) degradation. As per his observations, the chemical composition is sig-
nificantly effected together with gas production, metabolizable energy (ME), DM, and
CP degradability of the leaves of G. glabra by the maturity stage. Neutral detergent
fiber (NDF), acid detergent fiber (ADF), and condensed tannin (CT) contents increase
with increase in the maturity stage whereas crude protein decreases. Gas production,
DM, CP disappearance, and estimated parameters also decrease with increase in
maturity. CP, ADF, and CT contents range between 16.19 and 26.93%, from 20.74 to
29.07% and from 1.57 to 10.83%, respectively (Kamalak 2006). The potential gas
production and ME have been recorded to range from 65.34 to 72.12 ml/0.200 g of
DM and from 10.14 to 12.12 MJ/kg DM, respectively. The effective DM degradability
(EDMD) and effective CP degradability (ECPD) have given the values ranging
between 58.70 and 70.59% and from 57.32 to 73.72%. Gas production, DM and CP
disappearance, and estimated parameters of G. glabra leaves harvested at prebud stage
are significantly higher than those harvested at mid and late flower stages. Gas pro-
duction, DM and CP disappearance, and estimated parameters are negatively correlated
with NDF, ADF, and CT, but show a positive correlation with CP. G. glabra harvested
at the proper stage of maturity offers considerable potential as a high-quality forage for
ruminants during critical periods in the semiarid and arid regions (Kamalak 2006).

8.3.4 Use as Dye Plant

Different colors have been obtained from liquorice root without using mordant, with
the mordant alone, and with potassium bichromate mordant kept constant and the
two mordants mixed. These colors include open straw yellow, open henna green,
honey color, milky coffee, chick yellow, green yellow, dirty yellow, dry oak leaf,
open dirty yellow, open earth, hay yellow, open quince feather, dark quince feather,
open dry oak leaf, and dark dry oak leaf colors. These colors are the most used ones
in hand weaved carpets and rugs. These are strongly recommended for use in
environmentally friendly herbal dyeing of rugs and carpets (Arlı et al. 2002).
8.3 Other Uses 85

Arlı et al. (2002) have conducted a study on the colors obtained from G. glabra
root and their fastness values. They recommend that mordants should be used
singly; moreover, the colors obtained from the liquorice root in terms of light-
fastness are usually medium. For this reason, it is therefore suitable to use these in
the dyeing of carpets and rugs (Arlı et al. 2002).

8.3.5 Evaluation of Liquorice Wastes

G. glabra root extracts are commonly used for medicinal purposes as well as a
flavoring agent in the food and tobacco industries (Medina et al. 2011). Almost
10,000 tones of liquorice root residues annually accumulate in some countries and
must be properly treated, because the untreated residues produce unwanted envi-
ronmental effects as these are phytotoxic (Medina et al. 2011). Their direct appli-
cation to the soil is not suitable. No alternative use has been proposed for this waste
in recent evaluations. The burning of this waste is strictly forbidden. Landfilling is
costly; currently, nearly 40 dollars per ton are required to solve this problem which
includes the transportation cost as well. This type of application is regarded as
ecologically unfriendly solution, due to extensive production of greenhouse gases,
especially methane, under the anaerobic conditions prevailing in landfills (Lou and
Nair 2009; Medina et al. 2011).
Medina et al. (2011) have tried to develop a reliable protocol for management of
liquorice root wastes and their composting. They suggest that it is possible to use
these wastes as a peat substitute in growing media. They have also looked on their
suppressiveness against Fusarium oxysporum f. sp. melonis (FOM)—the causal
agent of Fusarium wilt of melon. According to Medina et al. (2011), these wastes
can be cocomposted. For this purpose, temperature-controlled forced aeration
system with the coarse fraction of separated cow manure can be used for an
enrichment both its nutrient content as well as microbial population. Thermophilic
conditions prevailing in the pile for approximately 3 months allow the compost to
get stabilized and reach an ambient temperature 110 days from the beginning. The
resulting compost shows physical characteristics which are well comparable to the
peat, with a high nutrient content and relatively low salinity, and no phytotoxicity is
seen in the extract from compost, according to the cress germination test. They have
grown tomato plants as well in compost which have shown enhancement in
development when compared to the peat. The number of surviving FOM spores
incubated in the compost has declined faster than in peat. Fusarium infected melon
plants have survived much better if planted in liquorice compost, as compared to
peat. It can be said that liquorice compost can serve as a peat substitute with
preferable qualities as proposed by Medina et al. (2011). Latter workers have
suggested that the waste can be successfully composted during a reasonable time
period, provided enough inoculum and sufficient nutrients are supplied, for
example, cattle manure. The composting duration of the chosen mix until full
compost maturity (110 days) is reported to be much shorter than that of liquorice
86 8 Economic Importance

waste alone (Hadar and Mandelbaum 1986) and comparable to that of most types of
organic matter, in spite of the recalcitrant nature of the waste from these roots
(Gagnon et al. 1999; Shi et al. 1999). Medina et al. (2011) have also proposed that
resulting compost has adequate chemical and physical characteristics for its use as a
component of growth media, and its performance has been clearly demonstrated.
The resulted compost has a potential nutritional effect, especially in terms of N and
K. The compost negatively affects the survival rate of FOM spores and shows
marked suppression against Fusarium wilt of melon. It therefore has a clear
potential as an ingredient of growth media (Medina et al. 2011).

8.3.6 Antimicrobial and Antifungal Activity

Lately, several clinical and pharmacological investigations have been undertaken,

which demonstrate the antimicrobial activities of liquorice aqueous, ethanol, and
supercritical fluid extract (Bodet et al. 2008; Park et al. 2008; Al-Turki et al. 2008;
Jain et al. 2013). Such an activity in plant oils and extracts has been recognized
since years. It has been indicated that it can be attributed to alkaloids, saponins,
flavonoides, tannin, glycosides, and phenols (Shinwari et al. 2009). Antimicrobial
activity of ethanolic extract of G. glabra has been tested against Bacillus subtilis
MTCC (121), Staphylococcus aureus MTCC (96), Pseudomonas aeruginosa
MTCC (429), Escherichia coli MTCC (443), and one fungal strain Candida albi-
cans. Candida albicans and Trichophyton rubrum growth have been reported (Patil
et al. 2009). The inhibition by ethanolic extracts of G. glabra and their fractions has
been shown by Meghashri (2009) as well. However, G. glabra methanolic extracts
seem to show more fungicidal effect against Arthrinium sacchari and Chaetomium
funicola (Hojo and Sato 2002). Tharkar et al. (2010) too have recorded the anti-
fungal activity of G. glabra extracts. Similarly, Gupta et al. (2008) have published
data related to the antimicrobial activity of G. glabra against Mycobacterium
tuberculosis. The liquorice extracts with ethanol, chloroform, and acetone show
antibacterial activity against Bacillus subtilis, Stapphylococcus aureus, Escherichia
coli, and Pseudomonas aeruginosa (Nitalikar et al. 2010). A high antibacterial
activity against Staphylococcus epidermidis, Staphylococcus aureus, and
Propionibacterium acnes has been recorded with G. glabra extracts (Nand et al.
2012). The antibacterial effect of G. glabra extract against Pseudomonas aerugi-
nosa, Shigella flexneri, Escherichia coli, Staphylococcus epidermidis, S. aureus,
and Baillus subtilis has been enlightened by Varsha et al. (2013). According to the
results published by Statti et al. (2004), G. glabra methanolic extract also shows
antimicrobial activity against various strains of Staphylococcus aureus ATCC
29213, Enterococcus faecalis ATCC 29212, Micrococcus luteus ATCC 9622,
Proteus mirabilis ATCC 29852, Proteus vulgaris ATCC 6361, and Escherichia
coli ATCC 4350. An antibacterial activity of G. glabra extracts against
Pseudomonas aeruginosa and B. subtilis has also been reported (Shinwari et al.
2009). The upper respiratory tract bacteria such as Streptococcus pyogenes,
8.3 Other Uses 87

Haemophilus influenza, and Moraxella catarrhalis studied by Tanaka et al. (2001)

reveal that secondary metabolites obtained from Glycyrrhiza species show
antibacterial activity against these. Licoricidin and coumarin derivatives like gly-
cyrol, glycyrin, and glycycoumarin too exhibit high activity against all tested
microorganisms. Glabridin derived from root of G. glabra has been found to be
active against both yeast and filamentous fungi (Fatima et al. 2009). It has shown
various biological activities like antimicrobial activity against Helicobacter pylori,
Staphylococcus aureus, and inflammation (Hatano et al. 2000; Fukai et al. 2002;
Nerya et al. 2003). G. glabra essential oils also show an inhibitory effect against
Aspergillus flavus (Ali 2013).
Two new pterocarpenes—glycyrrhizol A (1) and glycyrrhizol B (2)—with struc-
tures elucidated by spectroscopic data interpretation along with four known iso-
flavonoids—5-O-methylglycryol (3), isoglycyrol (4); both identified by comparison of
their spectroscopic data with reported values in the literature; 6,8-diisoprenyl-5,7,4′-
trihydroxyisoflavone (5), and gancaonin G (6)—have been isolated from the roots of G.
uralensis using a bioassay-guided fractionation method. Out of these, compounds 1 and
5 have shown potent antibacterial activity against Streptococcus mutans with minimum
inhibitory concentrations of 1 and 2 µg/mL, respectively, while glycyrrhizol B (2) and
gancaonin G (6) have shown more moderate activity (He et al. 2006). In all, 12
phenolic compounds have been isolated from the fractions of a supercritical fluid
extract of G. uralensis roots (Villinski et al. 2014). Seven of the metabolites from this
extract have been reported earlier. Moreover, four known components have been
characterized from this material for the first time, namely, 1-methoxyerythrabyssin II
(4), 6,8-diprenylgenistein, gancaonin G (5), and isoglycyrol (6), and one new isoflavan,
licorisoflavan C (7). When licoricidin (1) was treated by these workers with palladium
chloride larger amounts of licorisoflavan C (7) been produced together with two new
isoflavans, licorisoflavan D (8); subsequently detected in the liquorice extract; and
licorisoflavan E (9). A study on the antibacterial activity of compounds 1–9 against the
cariogenic Streptococcus mutans and the periodontopathogenic Porphyromonas gin-
givalis has revealed that licoricidin (1), licorisoflavan A (2), and 7–9 show antibacterial
activity against P. gingivalis (MICs of 1.56–12.5 lg/mL). Most potent activity against
S. mutans has been recorded with 7 (MIC of 6.25 lg/mL), followed by 1 and 9 (MIC
of 12.5 lg/mL). All these findings support the evidence for the therapeutic potential of
liquorice extracts for the treatment and prevention of oral infections (Villinski et al.
2014).
The compounds like 18b-glycyrrhetinic acid, liquiritigenin, glabridin, licochalcone
A, licochalcone E, licorisoflavan A, licoricidin, and glycyrrhizol A isolated from
liquorice possess antimicrobial effects against S. aureus, C. albicans, Mycobacterium
bovis, yeast, and several cariogenic bacteria like S. mutans and Streptococcus sobrinus
(Long et al. 2013; Fatima et al. 2009; Messier and Greiner 2011; Zhou et al. 2012a, b;
Dai et al. 2013; Kim et al. 2013b; Gafner et al. 2011; Hu et al. 2011).
According to Yang et al. (2015) liquorice has great application prospects as an
alternative therapy in treating dental caries, periodontal disease, digestive anabrosis,
and tuberculosis. It also has a potential alternative to synthetic fungicides, or as a
lead compound for new classes of synthetic fungicides (Yang et al. 2015).
88 8 Economic Importance

A new prenylated isoflavan, iconisoflavan (1), and a new prenylated

isoflav-3-ene, iconisoflaven (2) have been isolated from the roots of G. iconica
together with four known earlier (3S)-licoricidin (3), licorisoflavan A (4), topazolin
(5), and glycycoumarin (6) (Kırmızıbekmez et al. 2015). Their structures have been
elucidated on the basis of extensive spectroscopic analysis including 1D and
2DNMR as well as HR-MS. Kırmızıbekmez et al. (2015) have also established the
configurations of compounds 1, 3, and 4 by electronic circular dichroism (ECD).
An in vitro evaluation of all the isolated compounds (1–6) has revealed that they
show antimicrobial activities against five pathogenic bacteria and one yeast
(Candida albicans) using an in vitro microdilution method. Compounds 1 and 3–5
have displayed significant activity against Salmonella typhimurium ATCC 13311
with MIC values ranging from 2 to 8 lg/mL. All compounds have been screened
for their in vitro free radical scavenging activities using an in vitro microdilution
DPPH assay spectrophotometrically. The tested compounds have exhibited IC50
values in the range of 0.18–0.56 mg/mL. This suggests that they show an activity
comparable with that of ascorbic acid (IC50: 0.07 mg/mL). The investigations
undertaken by Kırmızıbekmez et al. (2015) are the first phytochemical and bioac-
tivity investigation on G. iconica.
Very important differences have been reported by Karahan et al. (2016) in the
antimicrobial and antioxidant activities of root extracts of G. glabra var. glan-
dulifera from different habitats in Hatay (Turkey). The extracts with most potent
antioxidant characteristics were those from populations originating from the regions
with similar climatic features (rainy Mediterranean climate and low-rain
Mediterranean climate). On the other hand, the extracts showing strongest
antimicrobial effect have come from the specimens originating from habitats under
anthropogenic pressure. This implies that the differences in the biological activities
can be attributed partly to the influence of environmental factors (Karahan et al.
2016).
An experimental work has been carried out by Gaur et al. (2016) to explore
in vitro as well as in vivo combination effects of liquiritigenin and isoliquiritigenin
isolated from G. glabra with b-lactam antibiotics (penicillin, ampicillin, and oxa-
cillin) against mec A-containing strains of methicillin-resistant Staphylococcus
aureus. Minimum inhibitory concentration (MIC) of the both components has
exhibited significant anti-methicillin-resistant Staphylococcus aureus activity (50–
100 lg/mL) against clinical isolates of methicillin-resistant Staphylococcus aureus.
In vitro combination study has shown that isoliquiritigenin significantly reduces
MIC of b-lactam antibiotics up to 16-folds, while liquiritigenin reduces up to
8-folds. Time-kill kinetics at graded MIC combinations (isoliquiritigenin/
liquiritigenin + b-lactam) have indicated 3.27–9.79-fold and 2.59–3.48-fold
reduction in the growth of clinical isolates of S. aureus, respectively. In S. aur-
eus-infected Swiss albino mice model, the combination of isoliquiritigenin with
oxacillin has significantly lowered the systemic microbial burden in blood, liver,
kidney, lung, and spleen tissues in comparison with isoliquiritigenin, oxacillin
alone as well as untreated control (Gaur et al. 2016). According to Gaur et al.
(2016), considering its synergistic antibacterial effect both isoliquiritigenin and
8.3 Other Uses 89

liquiritigenin prove to be the promising compounds for the development of novel

antistaphylococcal combinations.
Pandian and Chidambaram (2017) have succeeded in synthesizing “silver
nanoparticles” from aqueous extract of G. glabra. The biological reduction of these
particles has been carried out in appropriate condition and characterization of
synthesized nanoparticles followed by UV-Vis spectroscopy, FT IR, and SEM. The
phytochemicals present in the extract of G. glabra have reduced the silver ions into
metallic nanoparticles. The synthesized silver nanoparticle has exhibited a strong
antibacterial activity against P. aeruginosa and S. aureus. The synthesized SNPs
have exhibited potential anticancer activity and are reported to be nontoxic on
mammalian Vero cell line. Hence, the SNPs from plant extracts may be used to
develop nanomedicine against pathogens (Pandian and Chidambaram 2017).
Several reports clearly depict that liquorice has potent effects in inhibiting the
activities of gram-positive and gram-negative bacteria such as Staphylococcus
aureus (Long et al. 2013; Snowden et al. 2014; Lau and Plotkin 2013),
Porphyromonas gingivalis (Wittschier et al. 2009), Streptococcus mutans (Ahn
et al. 2012; Peters et al. 2010), Candida albicans (Irani et al. 2010; Fatima et al.
2009), Escherichia coli (Awandkar et al. 2012), Enterococcus faecalis (Badr et al.
2011), Pseudomonas aeruginosa (Yoshida et al. 2010), Helicobacter pylori (Asha
et al. 2013), and Bacillus subtilis (Irani et al. 2010). It also has effects in inhibiting
the activities of pathogenic fungi such as Alternaria solani, Botrytis cinerea, and
Phytophthora (Treutwein et al. 2010). The liquorice extracts with 80% methanol
(oil-based extract of liquorice) have shown great fungicidal effects against
Arthrinium sacchari M001 and Chaetomium funicola M002 (Hojo and Sato 2002).
An inhibitory effect of the G. glabra extract on Candida albicans and some
gram-positive bacteria has also been reported (Irani et al. 2010).
Attempts have been made to evaluate the antifungal activity as well as antitoxin
activity of G. glabra extract (Mohseni et al. 2014). Strain American Type Culture
Collection 15517 of Aspergillus parasiticus has been used to perform antifungal
susceptibility test. The tests have been followed according to clinical and laboratory
standards institute document M27-A3, and the rate of aflatoxin production was
determined using high-performance liquid chromatography technique after expo-
sure to different concentrations of liquorice extract. Mohseni et al. (2014) have
followed the quantitative changes in the expression of the aflR gene, analyzed by
measuring the cognate aflR mRNA level with quantitative real-time reverse tran-
scription polymerase chain reaction assay. Their results demonstrate the inhibitory
effect of liquorice extract on Aspergillus parasiticus growth at 500 mg/mL.
A significant decrease in aflatoxin production has been recorded at the same con-
centration. The production of aflatoxin B1 has been entirely inhibited in 10 g/mL of
the extract. A significant decrease has been observed in the level of aflR gene
expression has after exposure of fungal cells to 500 g/mL of extract. The antifungal
and antitoxin activities of the extract on Aspergillus parasiticus have revealed its
antifungal features together with its effective ability to decrease aflatoxin production
(Mohseni et al. 2014).
90 8 Economic Importance

8.3.7 Antiviral Activity

Several virus diseases including chronic hepatitis B and C, together with human
acquired immunodeficiency syndrome (AIDS), have been treated with licorice and
glycyrrhizate compounds obtained from the liquorice extract as a potential thera-
peutic agent (Wang et al. 2000; Chen et al. 2004; Orlent et al. 2006; Tandon et al.
2002). Many reports have indicated antiviral activity of glycyrrhizin and gly-
cyrrhizic acid with the ability to inhibit growth and cytopathology of hepatitis A
and C (Crance et al. 1990; Van Rossum et al. 1999), and immunodeficiency virus
(HIV) (Hattori et al. 1989; Plyasunova et al. 1992). The glycyrrhizin and its
derivatives from G. glabra do reduce the hepatocellular damage in chronic hepatitis
B and C, and show antiviral activity against HIV-1, SARS-related coronavirus,
respiratory syncytial virus, arboviruses, vaccinia virus, and vesicular stomatitis
virus (Fiore et al. 2008). Glycyrrhizin also shows antiviral effect, through an
inhibition of viral particle to cell membrane binding, or through cellular signal
transduction mechanisms (Crance et al. 2003). 18b-glycyrrhetinic acid is reported
as the promising biological alternative for the topical treatment of persistent vul-
vovaginal candidiasis (Pellatti et al. 2009). In vitro antiviral effects for viruses
causing respiratory tract infections like influenza virus and the severe acute respi-
ratory syndrome (SARS) coronavirus, human immunodeficiency virus (HIV) too
have been reported (Cinatl et al. 2003)
The potential use G. uralensis for treatment of human infection by enterovirus
type 71 (EV71) which can cause life-threatening meningoencephalitis has also been
investigated (Kuo et al. 2009). The treatment of viral hepatitis since the late 1970s
with liquorice preparations is a well-known fact. Recently, many papers published
depict that liquorice extract has significant antiviral activity against HIV, severe
acute respiratory syndrome-coronavirus (SARS), HSV, influenza virus (H3N2),
rotavirus, respiratory syncytial virus, varicella zoster virus, coxsackievirus, and
enterovirus (Booth et al. 2003; Wang et al. 2013a; Kwon et al. 2010; Shebl et al.
2012). As against this, as far as a single compound is concerned, many compounds
have been isolated from liquorice but only two triterpenoids, glycyrrhizin and
18b-glycyrrhetinic acid, have been reported to possess antiviral activity, with a
significant positive impact on HIV, H3N2, HSV, DHV, HCV, PrV, and IAV (Yang
et al. 2015). In addition, other virus types have been worked include the following:
H5N1, herpes virus, influenza virus, and rotavirus (Wolkerstorfer et al. 2009;
Matsumoto et al. 2013; Huang et al. 2012; Soufy et al. 2012; Michaelis et al. 2010;
Sasaki et al. 2002; Kang and Lieberman 2011; Smirnov et al. 2012; Moisy et al.
2012; Sui et al. 2010; Hardy et al. 2012a; Baltina et al. 2012; Yang et al. 2015). The
in vitro experiments with glycyrrhizin have shown that it inhibits HCV by sup-
pressing the release of infectious particles (Matsumoto et al. 2013), HSV by
depressing the cellular adhesion (Huang et al. 2012), influenza virus by reducing
HMGB1 binding to DNA and suppressing interactions between viral macro-
molecules and host proteins (Moisy et al. 2012), HIV by preventing the virus from
replication (Sasaki et al. 2002), and H5N1 not by interfering with H5N1 replication,
8.3 Other Uses 91

but by controlling H5N1-induced proinflammatory gene expression (Michaelis

et al. 2010). However, does glycyrrhizin inhibit virus replication still needs more
research work. It also interacts with the cell membrane and reduces endocytic
activity (Wolkerstorfer et al. 2009), and causes deregulation of generating the
mature forms of viral mRNA encoding, which is a process important for viral
stability (Kang and Lieberman 2011). The glycyrrhetinic acid is reported to show a
significant antiviral activity against rotavirus replication by reducing the amounts of
viral proteins VP2, VP6, and NSP2 at a step or steps subsequent to virus entry,
together with an effective inhibition of HIV-1 by reducing the accumulation of virus
antigen p24 and protecting cells from the cytopathogenic action of the virus (Hardy
et al. 2012a; Baltina et al. 2012).
In all, 13 new oleanane-type triterpenoid saponins, uralsaponins M-Y (1–13),
and 15 known analogues (14–28) have been isolated from the roots of G. uralensis
(Song et al. 2014). The structures of 1–13 have been identified on the basis of
extensive NMR and MS data analysis. The sugar residues have been identified by
gas chromatography and ion chromatography coupled with pulsed amperometric
detection after hydrolysis. For the first time, saponins containing a galacturonic acid
(1–3) or xylose (5) residue have been reported from Glycyrrhiza species.
Compounds 1, 7, 8, and 24 are reported to exhibit good inhibitory activities against
the influenza virus A/WSN/33 (H1N1) in MDCK cells with IC50 values of 48.0,
42.7, 39.6, and 49.1 lM, respectively, versus 45.6 lM of the positive control
oseltamivir phosphate. Moreover, compounds 24 and 28 have shown anti-HIV
activities with IC50 values of 29.5 and 41.7 lM, respectively (Song et al. 2014).
Adianti et al. (2014) have reported that glycycoumarin, glycyrin, glycyrol, and
liquiritigenin isolated from G. uralensis, as well as isoliquiritigenin, licochalcone A.
and glabridin, can be good candidates for seed compounds to develop antivirals
against HCV. Glycyrrhizin demonstrates a pronounced lymphocytic proliferation
response on white Pekin ducklings and reveals a good immune stimulant and
antiviral effect against DHV following in vivo studies (Soufy et al. 2012).
A protective effect is exerted by a combination of glutamyl-tryptophan and gly-
cyrrhizin in reducing the death of H3N2 virus-infected mice (Smirnov et al. 2012).
We can conclude that both glycyrrhizin and glycyrrhetinic acid exert antiviral
activity mainly by inhibiting the replication and release of the virus. They suppress
the interactions between the virus and host cells, activate immune responses in host
cells, and attenuate a virus-induced anti-inflammatory response (Yang et al. 2015).

8.3.8 Anti-inflammatory

The report published by Matsui et al. (2004) clearly shows that many allergies and
other inflammatory diseases have been treated with liquorice species. The
anti-inflammatory effects of glycyrol (benzofuran coumarin) isolated from G.
uralensis have been investigated at length (Shin et al. 2008). They found that
glycerols have potential anti-inflammatory effect. According to Vibha et al. (2009),
92 8 Economic Importance

the steroid-like anti-inflammatory activity of liquorice root constituents is similar to

the action of hydrocortisone. The explanation given by them in connection with this
finding is that it occurs due to inhibition of phospholipase A2 activity, an enzyme
critical to numerous inflammatory processes. The glycyrrhetinic acid (ED 50,
200 mg kg−1) is reported to show an inhibitory effect on carrageenan-induced rat
paw edema and anti-allergic activity (Matsui et al. 2004). G. glabra secondary
metabolites such as glycyrrhizic acid, glabridin, and licochalcone A also show an
anti-inflammatory effect (Furuhashi et al. 2005; Kang et al. 2005).
The liquorice looks like an excellent alternative choice for the treatment of
inflammation in the epidemic diseases among populations especially children
(Yang et al. 2015). A large number of reports stress the fact that two triterpenoids,
glycyrrhizin and 18b-glycyrrhetinic acid, and several flavonoids isolated from
liquorice such as glabridin, isoliquiritigenin, licochalcone A, licochalcone B, lic-
ochalcone C, licochalcone D, licochalcone E, isoangustone A, dehydroglyasperin
C, licoricidin, licorisoflavan A, echinatin, and glyurallin B, possess
anti-inflammatory activity (Yang et al. 2015). The effects of these compounds
(dehydroglyasperin C, echinatin, glycyrrhizin, 18b-glycyrrhetinic acid, licochal-
cone A, licochalcone B, licochalcone C, licochalcone D, licochalcone E, licoricidin,
licorisoflavan A, isoliquiritigenin, and glabridin) on different inflammatory types
have been investigated by different workers (Yang et al. 2015).
The types of inflammations studied are as follows: postischemic brain with
middle cerebral artery occlusion (Luo et al. 2013); chronic liver diseases (Imai et al.
2013); mastitis (Fu et al. 2014); acute lung injury (Ni et al. 2011); LPS-induced
inflammatory response (Wang et al. 2011; Furusawa et al. 2009); leishmania
donovani-infected macrophages (Bhattacharjee et al. 2012); indomethacin-induced
small intestinal damage (Ishida et al. 2013); ischemia/reperfusion (Oztanir et al.
2014); LPS-induced J774A.1 murine macrophages (Thiyagarajan et al. 2011);
periodontitis (La et al. 2011); lipid peroxidation in rat liver microsomes (Fu et al.
2013); LPS-induced BV-2 microglia (Kim et al. 2013c); glutamate-induced hip-
pocampal HT22 cells (Kim et al. 2012); childhood atopic dermatitis (Wananukul
et al. 2013); allergic airway inflammation (Chu et al. 2013); LPS-induced
RAW264.7 cell (Fu et al. 2013; Cho et al. 2010); LPS-induced macrophage cells
(Fu et al. 2013); in rat liver microsomes (Fu et al. 2013); LPS-induced macrophage
cells (Fu et al. 2013); LPS and interferon-gamma-induced inflammatory response
(Wang et al. 2013b); allergic inflammation (Tanifuji et al. 2010); and TPA-induced
mouse ear edema (Lee et al. 2013a), respectively.
In addition the about studies, Fuhr et al. (2015) have reported that in
TNF-a-stimulated colon cells, amorfrutin A (1) (isoprenoid-substituted benzoic
acid derivatives, which were found in G. foetida) significantly reduces the
expression and secretion of several inflammation mediators, in part due to inter-
action with PPARc. Fuhr et al.’s (2015) results support the hypothesis that amor-
frutins may have the potential to treat inflammation disorders such as chronic
inflammatory bowel diseases.
The glycyrrhizin has also been used in leishmania donovani-infected macro-
phages as per the in vitro studies published (Bhattacharjee et al. 2012). In
8.3 Other Uses 93

lipopolysaccharide-stimulated macrophage models, glycyrrhetinic acid, glabridin,

and isoliquiritigenin have been used and in actinobacillus actinomycetemcomitans
lipopolysaccharide-treated macrophages, licoricidin and licorisoflavan A have been
used (La et al. 2011). Licochalcone A, licochalcone B, and licochalcone E have
been used in lipopolysaccharide-induced RAW 264.7 macrophage cells (Fu et al.
2013; Cho et al. 2010), and DGC has been used in lipopolysaccharide-induced
BV-2 microglia and mice hippocampal cells (Wang et al. 2011; Thiyagarajan et al.
2011; Kim et al. 2012, 2013c).
Glycyrrhizin has also been used in the postischemic brain with a middle cerebral
artery occlusion mouse model both in vivo and clinical studies as well as in a
lipopolysaccharide-induced acute lung injury mouse model plus a mastitis mouse
model (Ni et al. 2011; Luo et al. 2013; Fu et al. 2014). For the treatment of
oxidative and neuronal damage in brain tissue caused by global cerebral ischemia/
reperfusion in a C57BL/J6 mouse model also glycyrrhetinic acid has been used
(Oztanir et al. 2014). In the childhood atopic dermatitis and in a murine model of
asthma licochalcone A has been used, whereas in TPA-induced mice ear edema
licochalcone E has been used (Wananukul et al. 2013; Chu et al. 2013; Yang et al.
2013; Lee et al. 2013a). Several studies show that liquorice extracts have benefits in
the treatment of acute and chronic inflammatory conditions, indicating that studies
on the anti-inflammatory activity of liquorice are very important and meaningful
(Nirmala and Selvaraj 2011; Wu et al. 2011; Yang et al. 2015).

8.3.9 Anti-ulcer

The anti-ulcer activity of deglycyrrhizinated liquorice formulations has been

demonstrated in Bennett et al. 1980 by Bennett and coworkers. They used a rat
model of aspirin-induced gastric mucosal damage. The results have shown that
these formulations promote healing by increasing mucous production and blood
supply to the damaged stomach mucosa, thus enhancing mucosal healing (Van
Marle et al. 1981; Da Nagao et al. 1996). An anti-ulcerogenic effect of carbenox-
olone derived from the root of liquorice too has been reported (Masoomeh and
Kiarash 2007). This is explained through an inhibition of the secretion of gastrin.
The reason is that liquorice compound raises the concentration of prostaglandins in
the digestive system and in this way promotes mucus secretion from the stomach.
Anti-pepsin effect of liquorice secondary metabolites too has been reported, which
prolongs the life span of surface cells in the stomach (Adel et al. 2005).

8.3.10 Anti Tumor

Almost all in vivo and in vitro studies on the liquorice phytochemical constitutes
have revealed that it has anticancer effects (Salvi et al. 2003). An inhibition of
94 8 Economic Importance

tumor formation and growth in breast, liver, and skin cancer has been reported (Liu
et al. 1998; Shiota et al. 1999; Tamir et al. 2000). In 1998, Fukai and his coworkers
reported the inhibitory activity of phenolic compounds such as isoliquiritigenin,
semilicoisoflavone B, gancaonin C licoisoflavone B, and licoisoflavanone for the
growth of both B. subtilis H17 (wild type) and M45 (recombinationless mutant
cells). In in vivo assay, Sheela et al. (2006) have observed that the extract of G.
glabra inhibits proliferation of tumor cells and angiogenesis. Antiproliferative
effects are displayed by the ethanolic extract and glycyrrhizin against the MCF-7 in
dose-dependent manner (Dong et al. 2007). Similar results have been reported by Jo
et al. (2005) who used ethanol extract of G. uralensis root which induced apoptosis
and G1 cell cycle arrest in MCF-7 human breast cancer cells. The licochalcone E
from the roots of G. inflata also exhibits most potent cytotoxic effect compared with
the known antitumor agents, licochalcone A, and isoliquiritigenin (Yoon et al.
2005). Many compounds have been derived from G. glabra, namely, glyasperin A,
gancaonin P, licochalcone B, topazolin, and gancaonin O by Nomura et al. (2002),
which have shown relatively higher cytotoxic activity against human oral squamous
cell carcinoma cell line HSC-2. A new retrochalcone derived from the G. inflata by
Yoon et al. (2005), during their studies on licochalcone E, has exhibited the potent
cytotoxic effect. Isoliquiritigenin has also been reported to inhibit the proliferation
of the human non-small cell lung cancer A549 cell line, inducing apoptosis and
locking cell cycle progression in the G1 phase (Hsu et al. 2004). Kanazawa et al.
(2003) too have reported similar findings, where isoliquiritigenin has inhibited the
growth of prostate cancer. It has been suggested as a chemopreventive compound
for cancer in humans. In short, the biologically active compound from the liquorice
root can be very useful as antiproliferative and antitumor agents (Rahman and
Rashid 2008; Hossain et al. 2004).
High mortality due to cancer is one of the leading causes of humans deaths; as
such, the use of natural compounds without side effects is currently attracting much
attention of researchers. Many studies have proven that various natural compounds
in liquorice possess effective antitumor activity, including three triterpenoids,
glycyrrhizin, glycyrrhetinic acid, and 11-deoxyglycyrrhetinic acid, and six flavo-
noids, isoangustone A, glabridin isoliquiritigenin, licochalcone A, licochalcone B,
and licochalcone E (Kim et al. 2010, 2013d; Hsu et al. 2011; Li et al. 2012; Kwon
et al. 2013; Khan et al. 2013; Lin et al. 2014; Yuan et al. 2014; Huang et al. 2014a;
Yang et al. 2015; Park et al. 2016).
The effects of these compounds (glycyrrhizin, 18b-glycyrrhetinic acid, 11-
deoxyglycyrrhetinic acid, isoangustone A, licochalcone A, licochalcone B, licochal-
cone E, isoliquiritigenin, and glabridin) on different cancer types such as colon car-
cinogenesis, leukemia, prostate cancer, gastric cancer, colorectal cancer, human
melanoma, liver cancer, bladder cancer, oral cancer, and breast cancer have been
investigated by different investigators (Shetty et al. 2011; Hsu et al. 2011; Xiao et al.
2011; Chueh et al. 2012; Khan et al. 2013; Lee et al. 2013b; Song et al. 2013; Kwon
et al. 2013; Wang et al. 2013c; Lin et al. 2014; Huang et al. 2014a; Tsai et al. 2014;
Choi et al. 2014; Yuan et al. 2014; Jiang et al. 2014; Kim et al. 2014). Several single
compounds isolated from liquorice as well as ethanol extracts and hexane/ethanol
8.3 Other Uses 95

extracts of roasted liquorice are reported to show antitumor activity (Seon et al. 2012;
Lee et al. 2013c). According to Yang et al. (2015), the liquorice compounds interfere
with antitumor activities mainly by attenuating the level of cytokines, blocking cell
cycle progression, and inducing cancer cell apoptosis. Isoangustone A has been applied
to SW480 human colorectal adenocarcinoma cells during in vitro studies, DU145 to
human prostate cancer cells as well as 4T1 murine breast cancer cells; isoliquiritigenin
to HeLa human cervical cancer cells and MDA-MB-231 to human breast cancer cells;
glycyrrhizin has been applied to WEHI-3 mouse leukemia cells, glycyrrhetinic acid to
DU-145 prostate cancer cells, and licochalcone to MKN-28, AGS, MKN-45 gastric
cancer cells, HA22T/VGH, SK-Hep-1, HepG2 to human hepatocellular cancer cells,
KB human oral cancer cells, and T24 to the bladder cancer cells (Wolkerstorfer et al.
2009; Shetty et al. 2011; Xiao et al. 2011; Chueh et al. 2012; Seon et al. 2012; Wang
et al. 2013c; Huang et al. 2014a; Tsai et al. 2014; Jiang et al. 2014; Choi et al. 2014;
Kim et al. 2014). Glycyrrhizin has also been applied under in vivo studies and has
shown to inhibit 1,2-dimethylhydrazine-induced colon precancerous lesions of Wistar
rats (Khan et al. 2013), while glycyrrhetinic acid applied to gastric cancer has inhibited
tumor growth in a nude mouse model (Lin et al. 2014). Glabridin has inhibited
MDA-MB-231 breast cancer angiogenesis in a nude mouse model; licochalcone B has
inhibited MB49 bladder tumor growth in a C57BL/6 mouse model; licochalcone E has
suppressed 4T1 mammary tumor growth and lung metastasis in the mammary fat pads
in a syngeneic BALB/c mouse model; isoangustone A has significantly suppressed
PTEN-deleted human prostate tumor growth and SK-MEL-28 human melanoma tumor
growth in xenograft mice models (Hsu et al. 2011; Kwon et al. 2013; Lee et al. 2013b;
Song et al. 2013; Yuan et al. 2014). In summary, liquorice embodies interesting and
important hits for antitumor drug discovery and development (Yang et al. 2015).

8.3.11 Antioxidant

The data published by Siracusa et al. in 2011 clearly depicts the fact that extract of
G. glabra leaves shows antioxidant, anti-genotoxic, and anti-inflammatory activi-
ties. Many phytochemical constitutes have been found in the roots of Glycyrrhiza.
These are considered as a potential source of antioxidants (Singh 2010; Lateef et al.
2012). According to Vaya et al. (1997), isoflavones glabridin and hispaglabridins A
and B show significant antioxidant activity. The luteolin, rutin, and apigenin fla-
vonoids found in the G. glabra roots show significant antioxidant characteristics
(Hesham and Shgeru 2002). The main compound linked to antioxidant activity is
mentioned as phenolic compounds (Škrovánková et al. 2012). The ethanol extract
of G. glabra has been reported to possess a cerebroprotective effect in hypoxic rats,
which may be mediated by its antioxidant effects (Muralidharan et al. 2009). G.
glabra essential oil also exhibits DPPH radical scavenging activity (85.2%) at dose
400 µg/ml (Ali 2013), whereas methanolic extract shows 91.3% scavenging
activity at dose of 62.5 µg (Lateef et al. 2012). Licochalcone C is reported to
possess antioxidant because it reduces the production of superoxide radicals and
96 8 Economic Importance

consequently reduces the activity of inducible nitric oxide synthase (iNOS)

(Franceschelli et al. 2011).

8.3.12 Hepatoprotective Activity

G. glabra is used in the traditional medicine to treat various liver diseases as well
(Subramoniam and Pushpangadan 1999). Secondary metabolites derived from
liquorice have been observed to lower serum liver enzyme levels and improve
tissue pathology in hepatitis patients (Van Rossum et al. 2001).
Isoflavan derivatives, glabridin, hispaglabridin A, hispaglabridin B, 4′-O-methyl-
glabridin, and 3′-hydroxy-4′-O-methylglabridin, isolated from G. glabra have been
investigated by Haraguchi et al. (2000) for their ability to protect liver mitochondria
against oxidative stresses. These workers have reported that mitochondrial lipid per-
oxidation linked to respiratory electron transport is induced nonenzymatically and an
inhibition of these isoflavans takes place. Hispaglabridin A strongly inhibits both
peroxidations and 3′-hydroxy-4′-O-methylglabridin, the most effective at preventing
NADH-dependent peroxidation. 3′-Hydroxy-4′-O-methylglabridin protects the mito-
chondrial respiratory enzyme activity against NADPH-dependent peroxidation injury
(Haraguchi et al. 2000). Moreover, dihydroxyfumarate—induced mitochondrial per-
oxidation is also prevented by this isoflavan. G. glabra isoflavans are highly effective in
protecting mitochondrial function against oxidative stresses (Haraguchi et al. 2000). G.
glabra root extract also shows radioprotective effect via lipid peroxidation in rat liver
microsomes and plasmid pBR322 (Shetty et al. 2002). The extract protects microsomal
membranes, which is evident from the reduction in lipid peroxidation, and could also
protect plasmid DNA from radiation-induced strand breaks (Shetty et al. 2002).
A significant reduction in serum aminotransferases is induced by glycyrrhizic
acid which then improves the liver histology (Curreli et al. 2007). Al-Razzuqi et al.
(2012) have demonstrated that G. glabra aqueous extract shows a significant effect
in ameliorating liver functions in acute liver diseases if given in a single dose per
day of 2 mg/kg body weight. The protective effects of glycyrrhetinic acid against
the carbon tetrachloride-induced hepatotoxicity and retrorsine-induced liver damage
has also been published by Jeong et al. (2002).
Only three compounds, glycyrrhetinic acid, glycyrrhizin, and dehydroglyasperin
C, have been reported until now to possess hepatoprotective activity, especially
glycyrrhizin, which according to Yang et al. (2015) is effective in almost the whole
process of liver diseases. During the clinical treatment of liver disease, glycyrrhizin
preparation has been widely used. After this date, it has been used on a large scale
in the treatment of a variety of liver diseases, such as hepatitis B, hepatitis C, liver
fibrosis, and cirrhosis of the liver (Yang et al. 2015). Glycyrrhizin has an obvious
protective effect in liver injury induced by CCl4 as revealed by different in vivo
animal models (Huo et al. 2011; Yin et al. 2011), together with hepatotoxicity
induced by xanthium, a-naphthyl isothiocyanates, and liver fibrosis (Zhai et al.
2007; Abe et al. 2008; Sharifzadeh et al. 2008). Moreover, glycyrrhizin,
8.3 Other Uses 97

glycyrrhetinic acid, and dehydroglyasperin C have also shown hepatoprotective

activity (Abe et al. 2008; Wang et al. 2012; Rasool et al. 2014; Tripathi et al. 2009;
Guo et al. 2013; Fujisawa et al. 2000; Chen et al. 2014b; Wu et al. 2008; Hasan
et al. 2014; Seo et al. 2014).
Some of the mechanisms that can lead to liver dysfunction are oxidative stress,
lipid peroxidation, and transaminase reactions. The downregulation of these factors
found recently enlightens the hepatoprotective effect of liquorice. It also exerts its
hepatoprotective effect by regulating the expression of CYP enzymes, attenuating
oxidative stress, improving the stability of the cell structure as well as biological
membrane systems, and inhibiting the cytolytic activity of the complement and
apoptosis systems (Yang et al. 2015). Latter also mentions that this extract sig-
nificantly inhibits the aspartate aminotransferase, alanine aminotransferase, and
alkaline phosphatase activities, and decreases total protein, albumin, and globulin
levels. The liver superoxide dismutase, catalase, glutathione peroxidase, glutathione
reductase, and glutathione S-transferase activities are also enhanced by this extract
together with glutathione level (Huo et al. 2011; Yin et al. 2011; Rasool et al. 2014;
Al-Razzuqi et al. 2012). Liquorice therefore appears to be a highly potent thera-
peutic agent for the treatment of liver diseases (Yang et al. 2015). The findings of
Park et al. (2016) are considered as scientific evidence that isoLQ in liquorice has
the function of being a hepatic protectant against oxidative damages through
ERK-mediated Nrf2 activation.

8.3.13 Dermatological Effect

As early as 1997 Lee and coworkers have observed many activities like skin
whitening, depigmenting, antiaging, anti-acne, and anti-erythemic affiliated to the
use of Glycyrrhiza root originating bioactive compounds. Recently, a significant
decrease in skin melanin by formulation of G. glabra extracts has been reported by
Akhtar et al. (2011). According to Lee et al. (2005), glycyrrhizin derived from the
root of G. glabra induces melanin formation; this is probably mediated through an
activation of a tyrosinase gene expression.

8.3.14 Antidepressant and Memory-Enhancing Activity

According to Dhingra and Sharma (2005, 2006), the mouse immobility tests have
clearly demonstrated that liquorice is highly effective as an antidepressant as well as
in the memory-enhancing activity. The studies undertaken by Zhao et al. (2006)
have revealed that liquiritin and many other secondary metabolites from G.
uralensis show an antidepressant effect on chronic stress following the experiments
carried out on the depressed rats. Wang et al. (2008) too have published data related
to the antidepressant-like activity of liquiritin and isoliquiritin in the forced
98 8 Economic Importance

swimming test (FST) as well as tail suspension test (TST) in mice. Latter have
depicted that an increase in the 5-Hydroxytryptamine and norepinephrine in the
mouse hippocampus, hypothalamus, and cortex could be the mechanism of action
of these compounds. The sedative and muscle relaxant activities in mice due to
another compound in liquorice the carbenoxolone in genetically epilepsy-prone rats
(GEPRs) have also been reported by Gareri et al. (2004). The studies on the root
extract of G. glabra on learning and memory in another experiment has revealed
that 150 and 225 mg/kg doses show an effective enhancement in learning and
memory as compared to the control. The reason may be antioxidant and
anti-inflammatory action of plant extract. Under these circumstances, the suscep-
tible brain cells get exposed to less oxidative stress resulting in reduced brain
damage and improved neuronal function (Chakravarthi et al. 2012).
A large number of workers have investigated the effects of liquorice aqueous
extract on learning and memory. One of these is Chakravarthi and Avadhani
(2014), who investigated the function of such extract in the dendritic morphology of
hippocampal cornu ammonis area three (CA3) neurons. According to these
workers, 150 and 225 mg/kg doses show obvious enhancement of dendritic
arborization and dendritic intersections in hippocampal pyramidal neurons. This has
demonstrated its neuronal dendritic growth stimulating features. These researchers
have also found that all doses of such an extract significantly enhances the memory.
An application of 150 and 225 mg/kg doses significantly enhance learning as well
as memory (Chakravarthi and Avadhani 2013). The nootropic and antiamnestic
effects of these extracts are mediated through augmenting monoaminergic trans-
mission in the cortex, hippocampus, and striatum (Michel et al. 2013).
Out of a large number of compounds isolated from liquorice glabridin and
2,2,4-trihydroxychalcone is reported to improve learning and memory. These are
commonly used in the treatment of cardiovascular and central nervous system
diseases (Yang et al. 2015). The higher doses of former compound effectively
antagonize amnesia induced by scopolamine (Cui et al. 2008). According to
Hasanein (2011), this compound also prevents the deleterious effects of diabetes on
memory and learning as per the experiments carried out on rats. Inhibition of
beta-site amyloid precursor protein cleaving enzyme 1 is regarded as an effective
strategy for anti-Alzheimerʼs disease drug discovery. As a new beta-site amyloid
precursor protein 2,2,4-trihydroxychalcone cleaving enzyme 1 inhibitor has been
tested to ameliorate impairment in mice (Zhu et al. 2010). All these findings
enlighten the fact that liquorice seems to be a promising drug for improving
memory, impaired learning, Alzheimerʼs disease, dementia, and other neurode-
generative disorders (Yu et al. 2007; Cui et al. 2008; Yang et al. 2015).

8.3.15 Immunoregulatory Activity

Most of the research work undertaken during the last decade reveals an
immunoregulatory activity of liquorice. Out of the liquorice compounds,
8.3 Other Uses 99

glycyrrhiza polysaccharides are believed to play an important role in stimulating the

bodyʼs immune ability, by affecting the bodyʼs nonspecific and specific immune
functions and through activating immune cells (Hong et al. 2009; Li et al. 2012). In
addition, glycyrrhizin, 18b-glycyrrhetinic acid, licochalcone A, liquiritigenin, gly-
cyrol, and glycyrrhiza polysaccharides also showed immunoregulatory activity
(Abe et al. 2003; Lee et al. 2009; Li et al. 2010a, 2012; Hendricks et al. 2012; Soufy
et al. 2012; Kim et al. 2013a; Ma et al. 2013; Fontes et al. 2014). The compounds
isolated from liquorice exert immunoregulatory activity by regulating the produc-
tion of cytokines and interleukin together with the expression of cell surface
molecules and immune responses (Yang et al. 2015). Many in vivo and clinical
studies have proved that these compounds produce a protective effect against dis-
seminated candidiasis (Lee et al. 2009). It reduces the severity of experimental
autoimmune encephalomyelitis as well (Fontes et al. 2014). It also increases the end
point serum antibody titers (Hendricks et al. 2012). The production of IL-10 also
increases with Con A-induced hepatitis (Abe et al. 2003). It acts as an immune
stimulant against DHV (Soufy et al. 2012). All these reports affirm the
immunoregulatory activity of liquorice and indicate that it can be developed as a
novel immunomodulatory drug (Yang et al. 2015).

8.3.16 Inhibitory Effect on Diabetes

Liquorice inhibits series of pathological and physiological changes induced by D-

galactose, such as insulin resistance and oxidative stress/free radical damage, so as
to delay the development of diabetes (Yang et al. 2015). Several compounds iso-
lated from licorice, such as glycyrrhizin, glycyrrhetinic acid, liquiritigenin,
isoliquiritigenin, glabridin, licochalcone A, licochalcone E, and some other flavo-
noids, have been reported to possess an inhibitory effect in diabetes (Choi et al.
2010; Lee et al. 2010; Sen et al. 2011; Yehuda et al. 2011; Park et al. 2012;
Alqahtani et al. 2013; Feng et al. 2013; Li et al. 2013; Wu et al. 2013; Gaur et al.
2014; Yao et al. 2014). The liquorice extract can be a highly potent therapeutic
agent for the prevention and treatment of diabetes nephropathy led by mesangial
fibrosis and glomerulosclerosis through blocking Akt activation and transforming
growth factor-b signaling (Li et al. 2010b). It alleviates blood glucose levels,
restores renal function, attenuates body weight loss, and modulates the adverse
effect of diabetes on renal glutathione and malondialdehyde as well as the activity
of catalase and superoxide dismutase. It also restores the total antioxidant capacity
of diabetic kidneys, and at the same time has a potential therapeutic effect in
diabetes due to its antioxidant and antihyperglycemic features (Kataya et al. 2011;
Saleem et al. 2011). All these reports indicate that liquorice is a highly potent
therapeutic agent for diabetes treatment (Yang et al. 2015).
The data published by Zhang et al. (2016) indicates that liquiritin has a pro-
tective effect against high fructose-induced myocardial fibrosis via suppression of
NF-kB and MAPKs signaling pathways. It may be a promising candidate for
100 8 Economic Importance

diabetes-related myocardial fibrosis treatment. Moreover, Xie’s (2017) results

indicate that liquiritigenin has a protective role in high fructose feeding-triggered
cardiac injury through fibrosis and inflammation response suppression by inacti-
vating NF-kB signaling pathway. Thus, liquiritigenin may be a potential candidate
for diabetes-associated cardiac injury (Xie 2017).

8.3.17 Adrenal Cortical Hormone-like Function

Some reports demonstrate that liquorice extracts and compounds show adrenal
cortical hormone-like function, increased adrenocorticotropic hormone formation,
and stimulated steroidogenesis in adrenal glands. It will also stimulate the secretion
of glucocorticoids, mineralocorticoids, and anterior pituitary corticotroph-releasing
hormone and vasopressin from the adrenal cortex (Lee et al. 2007; Kratschmar et al.
2011). Out of the compounds isolated from liquorice, 18b-glycyrrhetinic acid,
glycyrrhizin, and isoliquiritigenin produce an adrenal cortical hormone-like func-
tion (Yang et al. 2015). Isoliquiritigenin has significant estrogenic activities due to
its estrogen responsive b selectivity, partial estrogen agonist activity, and the
nonenzymatic transformation between isoliquiritigenin and liquiritigenin
(Hajirahimkhan et al. 2013). 18b-glycyrrhetinic acid and glycyrrhizin play a very
important role in the treatment of glucocorticoid-dependent diseases as a
well-known inhibitor of 11b-hydroxysteroid dehydrogenases (Kratschmar et al.
2011; Raikkonen et al. 2010; Sasaki et al. 2010). Glycyrrhetinic acid shows its
mineralocorticoid actions by inhibiting the conjugation of deoxycorticosterone and
dehydroepiandrosterone at a source within the adrenal cortex (Al-Dujaili et al.
2011). All the abovementioned findings lend support to the reasonable use of
liquorice as a promising strategy for the treatment of hormone-dependent diseases
(Yang et al. 2015).

8.3.18 Other Effects

A vast number of reports have been published on the pharmacological activities of

liquorice extracts and biologically active compounds. The secondary metabolites
liquiritigenin and isoliquiritigenin derived from the root of G. glabra have shown
dose-related anti-allergic activities (Kakegawa et al. 1992). Moreover, glabridin and
glabrene have an estrogen-like effect stimulating the synthesis of epithelial cell
DNA. It prevents postmenopausal women from vascular injury and atherosclerosis
(Kwon et al. 2008). According to Akasaka et al. (2011), glycyrrhetinic acid is
effective in suppressing pain-related behaviors caused by sciatic nerve injury.
Isoliquiritigenin has a spasmolytic effect on uterine contraction, an effective func-
tion in reducing pain, and an antiangiogenic property (Jhanji et al. 2011; Shi et al.
2012). The traditional compound prescription “gancao wheat jujube soup” has
8.3 Other Uses 101

demonstrated a potential antidepressant-like effect by liquiritin treatment in chronic,

variable, stress-induced depression; this can be related to the defense of liquiritin
against oxidative stress (Zhao et al. 2008). Liquorice is also used to relieve
menopausal symptoms in postmenopausal women (Menati et al. 2014;
Hajirahimkhan et al. 2015). Nagai et al. (2007) have indicated that licochalcone A
may be responsible for the relaxant activity of G. inflata root, which acts through
the inhibition of cAMP PDE.
Chen et al.’s (2009) results indicate that isoliquiritigenin plays a dual role in
regulating gastrointestinal motility, both spasmogenic and spasmolytic. The spas-
mogenic effect may involve the activating of muscarinic receptors, while the
spasmolytic effect is predominantly due to blockade of the calcium channels.
According to Mishra et al. (2011), anti-arthritic activity of G. glabra is due to its
significant reduction of paw edema volume and its ability to stabilize lysosomal
enzyme activity such as ACP. The results justify the benefit of G. glabra in the
treatment of inflammation associated diseases like arthritis. The investigations
carried out by Asgary et al. (2007) have revealed that G. glabra extract has an effect
of on the blood lipids and atherosclerosis. These workers have found that G. glabra
extract significantly decreases total cholesterol (TC), low-density lipoprotein
cholesterol (LDL-C), and triglyceride (TG) levels and increases high-density
lipoprotein cholesterol (HDL-C) and lessens atherosclerotic lesion in aorta. Won
et al. (2007) have reported the use of liquorice as a food ingredient for obesity,
because licochalcone A derived from G. uralensis reduces the lipase activity as a
new inhibitor of pancreatic lipase.

8.3.18.1 Clinical Therapeutics

Many reports about the clinical applications of liquorice ingredients and prepara-
tions have been published as the modern pharmacology developed (Yang et al.
2015). The development of glycyrrhizin preparations, mostly used to treat liver
diseases, has a long history in Asia among all active compounds isolated from this
plant (Li et al. 2014). This preparation has developed four generations so far, from
glycyrrhizin tablets to ammonium glycyrrhizinate, diammonium glycyrrhizinate,
and magnesium isoglycyrrhizinate. A comparison with its first three preparations,
magnesium isoglycyrrhizinate has a better lipotropy, higher targeting, and fewer
adverse reactions, because of its use in protecting hepatic L02 cells from ischemia/
reperfusion-induced injury (Huang et al. 2014b). It has been successfully used to
slow down the process of pulmonary fibrosis (Xiao et al. 2014), inhibiting
ethanol-induced testicular injury (He et al. 2010), and restoring hepatic impairments
caused by paclitaxel in other cancer treatments (Chen et al. 2014a).
The addition of liquorice and its active compounds to the oral cortisone acetate
increases the amount of cortisol available to tissues in Addisonʼs disease (Methlie
et al. 2011). A double-blind clinical trial study conducted on patients with allergic
rhinitis has shown that the rate of its symptoms including severe rhinorrhea, sneeze,
pruritus, and congestion are lowered significantly after using glycyrrhizin nasal
102 8 Economic Importance

drops (Akhavan et al. 2012). According to Agarwal et al. (2009), the liquorice
gargle is effective in attenuating the incidence and severity of postoperative sore
throat. Jain et al. (2013) have reported that both aqueous and ethanolic extracts of
this plant exert cariostatic activities through a clinical trial carried out among 60
pediatric patients aged 7–14. With the discovery of more and more pharmacology
activities, liquorice has shown a great potential for acting as a novel drug or
complement agent to treat different diseases (Yang et al. 2015).

8.3.19 Side Effects and Toxicity

The toxic effects of liquorice are well documented, but potentially toxic compounds
in it have not been confirmed fully. According to Asl and Hosseinzadeh (2008),
although deglycyrrhizinated liquorice (DGL) is reported to be free of adverse
effects, the large amounts of this plant may result in severe hypertension, hypo-
kalemia, and other signs of mineralocorticoid excess. The doses exceeding 10 times
the standard dose when consumed over a long period can lead to a number of
dangerous conditions (McGuffin et al. 1997). The use of this plant is contradicted in
persons with high blood pressure due to hypertension caused by its overuse, which
may be due to its effect on the aldosterone system; however, a treatment with its
extract results in dose-dependent increase in plasma renin and sodium with con-
comitant decrease in plasma cortisol, adrenocorticotropic hormone (ACTH),
aldosterone, and potassium levels (Olukoga and Donaldson 2000; Al Qarawi et al.
2002; Sharma and Agrawal 2013). Its prolonged use leads to hypertension, hypo-
kalemia, and edema, since insulin-dependent diabetics appear to be predisposed to
hypokalemia and sodium retention, and use of this plant is contradicted by diabetes
(McGuffin et al. 1997; De Smet et al. 1997; Asl and Hosseinzadeh 2008; Isbrucker
and Burdock, 2006). This plant should not be used with stimulant laxatives or
hypotensive diuretics (such as thiazides) because of the potassium loss associated
with the laxatives and diuretics (De Smet et al. 1997; Asl and Hosseinzadeh 2008).
Glycyrrhizin has been shown to interfere with 5b-reductase breakdown of corti-
costeroids, thus prolonging the biological half-life of these steroids. The gly-
cyrrhizin or the aglycone, or glycyrrhetinic acid are reported to increase the effect of
corticoid treatment (Brinker 1997).
Some studies on liquorice report (ethanol extracts of G. glabra), containing
glycyrrhizin and glycyrrhetic acid, negative results in the TA98 and TA100 strains
(Mitscher et al. 1986; Zani et al. 1993). Genotoxic potential of G. glabra has been
investigated using the Ames IITM, chromosomal aberration, and micronucleus test
systems. The results indicate that this plant possesses no mutagenic activities, either
with or without metabolic activation (Nakagawa et al. 2008; Chandrasekaran et al.
2011). TA98 has been reported to be more sensitive to the mutagens present in the
liquorice water extract (Martinez et al. 1999). The cytotoxic activity of liquorice
extract is 63% at 0.24 mg/mL, with greater percentages apparent as its concen-
trations increase up to 4.8 mg/mL. IC50 values of chloroform, methanol, and water
8.3 Other Uses 103

extracts of G. glabra in the breast MCF7 cell line have been reported as 0.45, 0.99,
and 1.29 lM, respectively (Rathi et al. 2009). Abudayyak et al. (2015) have
reported that G. glabra water extract displays mutagenic activity against the TA100
strain in the presence of metabolic activation, but only at the highest extract con-
centration. It has been reported that large doses or long-term injections of this plant
extract sometimes produce an acquired form of apparent mineralocorticoid excess
syndrome, expressed as sodium retention, hypokalemia, and high blood pressure
(Wang and Nixon 2001; Shen et al. 2007).
The medical records of patients treated with liquorice herbal complexes from
January 1 to December 31, 2010 have revealed changes in the levels of creatinine,
potassium, and blood urea nitrogen before and after herbal complex intake and the
prevalence of hypokalemia among these patients. A total of 360 patients have not
shown significant changes in the levels of potassium and creatinine (p = 0.815 and
0.289, respectively). Hypokalemia has been observed in six patients; however, in five
patients, the hypokalemia did not appear to be related to liquorice. The results show that
herbal complexes containing liquorice have not significantly influenced the potassium
levels in routine clinical herbal therapies (Jung et al. 2014). 4T1 mammary carcinoma
cells injected into the mammary fat pads of syngeneic BALB/c mice have revealed that
7 days after the injection, the mice received licochalcone E (7 or 14 mg/kg body
weight/day) via oral gavage for 25 days. Licochalcone E suppresses solid tumor
growth and lung metastasis, without exhibiting kidney or liver toxicity (Kwon et al.
2013). Russo et al. (2000) have proposed that some people could be susceptible to low
doses of glycyrrhizin because of a 11b-hydroxysteroid dehydrogenase deficiency.
Harahap et al. (2011) believe that liquorice ingestion and mutations in the HSD11B2
gene, inhibit 11b-hydroxysteroid dehydrogenase type 2 enzyme activity and cause the
syndrome of apparent mineral corticoid excess. This supposed that liquorice ingestion
is an environmental risk factor for hypertension or an apparent mineral corticoid excess
state in patients with a mutation in HSD11B2.
The liquorice is generally recorded as a nontoxic herb in TCM but some health
concerns have been reported with its use (Kao et al. 2014). It causes edema and
apparent mineralocorticoid excess syndrome as per the clinical studies, because gly-
cyrrhizic acid and glycyrrhetinic acid inhibit the activity of 11b-hydroxysteroid
dehydrogenase type 2 (11b-HSD2) which converts biologically active cortisol into the
inactive compound cortisone, thereby preventing the overstimulation of the mineralo-
corticoid receptor by cortisol (Whorwood et al. 1993; Ma et al. 2011; Hardy et al.
2012b). An overdose of the latter can lead to excessive sodium ion levels and the
excretion of potassium ions, which end up with water retention and lead to hyper-
tension. Its excessive daily supplementation may cause low potassium levels due to
liquorice-induced hyperaldosteronism and finally hypertension and heart disease. The
hypertension induced by its use can be reversed by stopping its intake as well as intake
of its products (Ruiz-Granados et al. 2012). 11b-Hydroxysteroid dehydrogenase type 2
is inhibited by liquorice and its constituents; this causes hypertonia and hypokalemia
because of the associated change in blood potassium levels. Similar concerns are
associated with the intake of carbenoxolone because it is a more potent inhibitor of
11bHSD2 (IC50: 20–50 nM) than 11bHSD1 (IC50: 1.8 lM) (Ma et al. 2011).
104 8 Economic Importance

Potassium levels are also affected by digoxin (Bielecka-Dabrowa et al. 2012), which
might act synergically with liquorice herbal intake. Some products use deglycyrrhiz-
inated liquorice (DGL) instead of raw extract; this reduces glycyrrhizic acid and gly-
cyrrhetinic acid-induced side effects (Kao et al. 2014).
An overuse of liquorice also influences the effects of other medicines. Glabridin
may inhibit human cytochrome P450 (Kent et al. 2002) which metabolizes warfarin
(coumadin), an anticoagulant agent, into its inactive form (Cavallari and Limdi
2009), and is an important enzyme in drug metabolism and bioactivation
(Guengerich 2008). The liquorice increases warfarin clearance and in case treatment
with warfarin is required, consulting a physician is strongly advised before con-
suming foods containing liquorice (Mu et al. 2006; Kao et al. 2014).
Pregnant females should limit intake of extract from this plant (Kao et al. 2014).
Very few investigations have been conducted on the teratogenicity of its extract, but
a single study has indicated that it may aggravate cyclophosphamide-induced body
weight loss and malformations of fetuses by upregulating cytochrome P450 type 2B
(Park et al. 2011). However, Korean researchers have reported that women taking
liquorice for the treatment of cough and cold did not have an increased risk of
stillbirths (Choi et al. 2013). Its extract also increases estrogen levels in humans
(Armanini et al. 2002) and may increase the risk of estrogen-mediated cancer
(Boucher et al. 2012). The extract of this herb can potentially cause an antian-
drogenic effect, which may lead to erectile dysfunction, therefore to avoid such side
effects, careful intake of this herb-related food is highly advised (Armanini et al.
2003; Zamansoltani et al. 2009; Kao et al. 2014).

8.3.19.1 Mycotoxin Contamination in Liquorice Products

The microbial growth on liquorice roots is highly expected because of the effects of
the environmental conditions (Khalesi et al. 2013). An exposure to the fungal
contamination is seen due to old-style harvesting, processing, and storage condi-
tions. Such a contamination has three main effects: deterioration of the chemical
composition, reduction of the medicinal effectiveness, and the risk of mycotoxin
production (Khalesi 2015). The presence of aflatoxin B1 (AFB1) has been reported
to be much lesser extent than ochratoxin A (OTA) on its roots but the reasons are
unknown (Pietri et al. 2010; Wang et al. 2013d). According to a recent report
published by Pietri et al. (2010), only 16% of the products from this herb contained
AFB1, but majority contained OTA, sometimes up to 990.1 ng/g. In view of this, a
large number of papers have been published mainly on the OTA contamination of
its products (Khalesi 2015).
The presence of OTA in this herb preparation has been reported for the first time
by Bresch et al. (2000) and Majerus et al. (2000). They have reported a high
percentage of contaminated samples. The report from the former authors mentions
that nearly 50% of the liquorice roots showed OTA contamination in the concen-
tration range of 0.3–216.0 ng/g. The homogeneous brownish samples have been
reported to contain higher amounts of OTA than bright yellow ones, which is quite
8.3 Other Uses 105

interesting. In another study Majerus et al. (2000) have analyzed 83 liquorice

products, as foodstuff or supplements of medicine, all these have indicated low
levels of OTA in children’s tea (130–440 ng/g), but quite high levels in supple-
ments (300–64300 ng/g). More than 90% of liquorice tablets have been reported to
contain OTA in the range of 700–2600 ng/g. Many more studies have confirmed
high amounts of OTA in liquorice products, sometimes with values above 200 ng/g
(Kabelitz and Sievers 2004).
The Italian liquorice products too have been reported to contain OTA, while its
confectionery contained 0.96 ng OTA/g, dried extracts had 89.6 ng OTA/g with the
maximum value of 990.1 ng/g, which represents an extremely high level of con-
tamination. In the light of these reports, OTA intake from dried liquorice extract
seems to expose a risk for consumers, especially high consumers, patients, and
infants (Pietri et al. 2010; Khalesi 2015).
Ariño et al. (2007a) have also reported high levels of OTA in 30 liquorice
products from Spain, including food as well as medicine-based samples. They have
reported OTA concentrations up to 252.8 ng/g. Dry liquorice roots contained the
highest levels with the mean value of 63.6 ng/g and sweets contained the lowest
level with the average value of 3.8 ng/g. The extract of the herb contained 16.0 ng
OTA/g and its solid blocks had 39.5 ng OTA/g. These workers have also notified
that OTA in dry roots may be shifted to corresponding tea from 1% for infusion tea
and up to 5% in the case of decoction tea. Nearly 75% of the liquorice hard candies
purchased from public markets in Spain are reported to show OTA contamination,
with a mean value of 2.96 ng/g, while for the soft candies, contamination is only
39%, with a mean value of 0.34 ng OTA/g sample (Herrera et al. 2009).
In China OTA levels in its roots have revealed that the highest level of con-
tamination occurred in the samples from Jiangxi (84.4 ng/g) and the lowest from
Beijing (1.4 ng/g) (Yang et al. 2010). The ecophysiological and storage conditions
may be responsible for the differences together with the variety of the roots. This
enlightens the findings that the region of collection plays a significant role for OTA
amount. The sustainability of the roots against contamination may be different from
one place to another (Khalesi and Khatib 2011; Khalesi 2015).
The risk of fungal contamination of its roots increases in warm humid areas
(Khalesi et al. 2013; Khalesi 2015). Large quantities of the roots are typically
stocked for a long period before processing or transportation. A successful approach
to avoid contamination is managing the storage conditions (Kapetanakou et al.
2009; Cairns-Fuller et al. 2005). Khalesi and Khatib (2011) and Khalesi (2015)
have studied the relation between OTA biosynthesis and ecophysiological factors
including temperature, water activity (aw), and type of mycobiota in the region at
length. Recent reports demonstrate that temperature of 22 °C is the critical point to
control the formation of OTA in these roots; below this temperature, the amount of
OTA is much lower than the temperatures mentioned. The covering of bulk of the
roots during the storage needs to be avoided, as it may increase the inlet temper-
ature and, consequently, the risk of fungal growth as well as OTA biosynthesis
(Khalesi et al. 2013; Khalesi 2015).
106 8 Economic Importance

The major parameter influencing OTA formation is the mycobiota in a region of

liquorice root, which should be particularly considered. The distributional map of
the fungi in liquorice production regions is still missing (Khalesi 2015). In all, 16
fungal species have been isolated from the root samples collected from four dif-
ferent locations in China, major ones being Penicillium, Aspergillus, and Eurotium
(Chen et al. 2011). P. polonicum is the main species in Jiangxi province (with
highest levels of OTA), whereas in other regions, Aspergillus spp. such as A.
parasiticus, A. flavus, A. versicolor, and A. sydowii and Eurotium spp. such as E.
chevalieri, E. repens, and E. amstelodami are dominant. Similar investigations were
undertaken by Chen et al. (2013). They reported that Penicillium is the major
fungus on liquorice in different regions in China with potential of OTA production.
They also isolated two new Penicillium species, i.e., P. glycyrrhizacola sp. nov. and
P. xingjiangense sp. nov. in the roots of this herb for the first time. P. chrysogenum
was also reported as one of the main OTA producers on roots in China. Chen et al.
(2013) have reported that P. chrysogenum, P. glycyrrhizacola, P. polonicum, and A.
westerdijkiae are main contaminants in dry liquorice with values lying around
39.03 ng/g. However, the data for fresh and dry specimens on mycobiota differs
much (Khalesi 2015).
No public reports are available from Iran concerning the mycobiota in the
regions where this herb flourishes (Khalesi 2015). However, after observation of
OTA, biodegradation on its roots from the natural contamination by A. fumigatus,
A. japonicus, and A. niger is possible. Khalesi et al. (2011) have hypothesized that
there may be predominant in OTA producers in Iran.
In case fungal contaminated liquorice is consumed for a long time, this may
cause health hazards such as, chronic hypokalemic nephropathy secondary which
needs immediate attention (Vivekanand 2010; Khalesi 2015). However, the fun-
damental mechanism of OTA toxicity has not been fully enlightened (Khalesi
2015). But some investigations have been done to decrease the risk by possible
intake of OTA contaminated herbal product. Some research has been conducted on
different food-based liquorice products as a normal dietary use to complete the
current consumption databases of European Food Safety Authority (EFSA) con-
cerning OTA in liquorice products (Commission Regulation (EU) No. 105/2010).
According to Pietri et al. (2010), assuming a total mean value of 1.53 ng OTA/g in
sweets corresponding to consumption about 1.4 g liquorice sweets per day means a
weekly intake of 12 ng OTA. For an infant with 30 kg weight, a weekly uptake of
0.4 ng/kg body weight has been reported which is extremely high. In another study,
it has been shown that children may consume up to 8.94% tolerable weekly intake
(TWI) of liquorice confectionary (Herrera et al. 2009). Although liquorice and its
derivatives are not the dominant products in dietary intake, for high consumers of
this herb, especially children, yet the current amount of OTA in its products is not
safe (Khalesi 2015).
At present, the main issue for trading the liquorice products, especially those
coming from Asia, is keeping the products safe concerning OTA (Khalesi 2015).
To fulfill this criterion, efforts have been made to regulate OTA levels in this herb
(Commission Regulation (EU) No. 105/2010). For this purpose, first, the data of
8.3 Other Uses 107

OTA concentration in a variety of its products obtained from public markets has
been collected. Commission Regulation (EU) No. 105/2010 amending regulation
(EC) No. 1881/2006 sets the regular maximum levels of 20 ng/g for its root and
80 ng/g for the extract. The reason for the difference between the maximum
acceptable amount of OTA between root and extract is that from each 3 to 4 kg
liquorice roots, around 1 kg of extract is obtained. These rules and calculations are
valid for average consumers. Of course for the high consumers, patients, and
infants, these amounts need to be reviewed (Khalesi 2015).
The liquorice (Glycyrrhiza taxa) plants have a large number of applications in
food and pharmaceutical industry. If these are contaminated by fungal OTA, the
possibility for a carcinogenic mycotoxin production during growth and storing
period can be expected (Khalesi 2015). In EU, the maximum amount of OTA in its
roots and extract has been authorized at 20 and 80 ng/g, respectively. Nevertheless,
a valid method to quantify this toxin is still lacking. Use of IAC and SPE clean-up
methods followed by liquid chromatography has been proposed for determination
of OTA in the products of this herb. However, those methods are time-consuming,
laborious, costly, and restricted to only a few laboratories, mostly located in
Europe. The decontamination of OTA in this herb is also a very challenging topic.
Peeling, extraction, and dehydration have been reported to reduce the amount of
OTA. Although thermal stability of OTA is an obstacle for heat deterioration of this
mycotoxin in the roots of this herb and derived products, it seems that much more
studies on determination and decontamination of OTA are needed to overcome the
OTA concern in liquorice marketing (Khalesi 2015).

8.3.20 Other Alternative Uses

Abdel-Latif et al. (2015) have studied three natural dyes extracted from Biota
orientalis, Piper nigrum, and Glycyrrhiza glabra. They have used these as pho-
tosensitizers for dye-sensitized solar cells (DSSCs). The dyes have been tested as
sensitizers before and after grinding the materials. Titanium dioxide (TiO2)
nanopowder has been used as a semiconducting material. The best photovoltaic
performance has been recorded from the DSSC sensitized with G. glabra after
grinding the material. They suggest that this performance is significantly improved
by acid treatment of the TiO2 photoelectrode. Electrochemical impedance spec-
troscopy of the fabricated DSSCs has been carried out and charge recombination
resistance, double layer capacitance, effective lifetime of electrons, charge transfer
resistance, and constant phase element exponential coefficient determined
(Abdel-Latif et al. 2015).
The studies carried out by Ovez et al. (2006) deal with one natural organic
substance liquorice (G. glabra) for its use as a carbon source in the biological
denitrification of drinking water. This material acts as a solid substrate and biofilm
carrier. Their experiments have been carried out in batch, semi-batch, and contin-
uous processes. Complete denitrification has been achieved with G. glabra. They
108 8 Economic Importance

found that nitrate removal rate of G. glabra is 6.96 mg/L/day NNO3. The results of
Ovez et al. (2006) have clearly revealed that this organic substrate could be used as
an alternative carbon source for denitrification with complex process control and
continuous monitoring, but this carbon source should be changed periodically for
the continuation of the process.

References

Abdel-Latif MS, El-Agez TM, Taya SA, Ghamri HS, Batniji AY (2015) Dyes extracted from
Biota orientalis, Piper nigrum, and Glycyrrhiza glabra as photosensitizers for dye-sensitized
solar cells. Int J Renew Energy Res 5(4):1034–1040
Abe M, Akbar F, Hasebe A, Horiike N, Onji M (2003) Glycyrrhizin enhances interleukin-10
production by liver dendritic cells in mice with hepatitis. J Gastroenterol 38:962–967
Abe K, Ikeda T, Wake K, Sato T, Sato T, Inoue H (2008) Glycyrrhizin prevents of
lipopolysaccharide/D-galactosamine-induced liver injury through down-regulation of matrix
metalloproteinase-9 in mice. J Pharm Pharmacol 60:91–97
Abudayyak M, Nath EO, Ozhan G (2015) Toxic potentials of ten herbs commonly used for
aphrodisiac effect in Turkey. Turk J Med Sci 45:496–506
Adel M, Alousi LA, Salem HA (2005) Licorice: a possible anti-inflammatory and anti-ulcer drug.
AAPS Pharm Sci Tech 6:74–82
Adianti M, Aoki C, Komoto M, Deng L, Shoji I, Wahyuni TS, Lusida MI, Soetjipto, Fuchino H,
Kawahara N, Hotta H (2014) Anti-hepatitis C virus compounds obtained from Glycyrrhiza
uralensis and other Glycyrrhiza species. Microbiol Immunol 58(3):180–187
Agarwal A, Gupta D, Yadav G, Goyal P, Singh PK, Singh U (2009) An evaluation of the efficacy
of licorice gargle for attenuating postoperative söre throat: a prospective, randomized,
single-blind study. Anesth Analg 109:77–81
Ahn SJ, Cho EJ, Kim HJ, Park SN, Lim YK, Kook JK (2012) The antimicrobial effects of
deglycyrrhizinated Licorice root extract on Streptococcus mutans UA159 in both planktonic
and biofilm cultures. Anaerobe 18:590–596
Akan H, Balos M (2008) GAP Bölgesi’nden toplanan meyan kökü (Glycrrhiza glabra L.)
taksonunun ihracat durumu, etnobotanik özellikleri ve tıbbi önemi. Fırat Üniversitesi Fen ve
Mühendislik Bilimleri Dergisi 20(2):233–241 (In Turkish)
Akasaka Y, Sakai A, Takasu K, Tsukahara M, Hatta A, Suzuki H, Inoue H (2011) Suppressive
effects of glycyrrhetinic acid derivatives on tachykinin receptor activation and hyperalgesia.
J Pharmacol Sci 117:180–188
Akhavan A, Saberi M, Saberi F (2012) Topical effects of Glycirrhizic acid on allergic rhinitis in
comparison to the beclomethazone treatment. J Med Plants 11:120–129
Akhtar N, Khan MS, Iqbal A, Khan BA, Bashir S (2011) Glycyrrhiza glabra extract cream: effect
on skin pigment melanin. In: Proceeding book of international conference on bioscience,
biochemistry and bioinformatics, IPCBEE, IACSIT Press, Singapore
Al-Dujaili EA, Kenyon CJ, Nicol MR, Mason JI (2011) Liquorice and glycyrrhetinic acid increase
DHEA and deoxycorticosterone levels in vivo and in vitro by inhibiting adrenal SULT2A1
activity. Mol Cell Endocrinol 336:102–109
Ali EM (2013) Phytochemical composition, antifungal, antiaflatoxigenic, antioxidant, and
anticancer activities of Glycyrrhiza glabra L. and Matricaria chamomilla L. essential oils.
J Med Plants Res 7(29):2197–2207
Alqahtani A, Hamid K, Kam A, Wong KH, Abdelhak Z, Razmovski-Naumovski V, Chan K,
Li KM, Groundwater PW, Li GQ (2013) The pentacyclic triterpenoids in herbal medicines and
their pharmacological activities in diabetes and diabetic complications. Curr Med Chem
20:908–931
References 109

Al-Qarawi AA, Abdel-Rahman HA, Ali BH, El Mougy SA (2002) Liquorice (Glycyrrhiza glabra)
and the adrenal-kidney-pituitary axis in rats. Food Chem Toxicol 40(10):1525–1527
Al-Razzuqi RAM, Al-Jawad FH, Al-Hussaini JA, Al-Jeboori AA (2012) Hepatoprotective effect
of Glycyrrhiza glabra in carbon tetrachloride-induced model of acute liver injury. J Phys
Pharm Adv 2(7):259–263
Altay V, Karahan F, Öztürk M, Hakeem KR, Ilhan E, Erayman M (2016) Molecular and
ecological investigations on the wild populations of Glycyrrhiza L. taxa distributed in the East
Mediterranean Area of Turkey. J Plant Res 129(6):1021–1032
Al-Turki AI, El-Ziney MG, Abdel-Salam AM (2008) Chemical and anti-bacterial characterization
of aqueous extracts of oregano, marjoram, sage and licorice and their application in milk and
labneh. JFAE 6:39
Anonymous (2005) Glycyrrhiza glabra. Altern Med Rev 10:230–237
Ariño A, Herrera M, Langa E, Raso J, Herrera A (2007a) Ochratoxin A in liquorice as affected by
processing methods. Food Addit Contam 24(9):987–992
Ariño A, Herrera M, Estopañan G, Juan T (2007b) High levels of ochratoxin A in licorice and
derived products. Int J Food Microbiol 114:366–369
Arlı M, Kayabaşı N, Kızıl S (2002) A research on the colours obtained from licorice (Glycyrrhiza
glabra L.) plant in natural dyeing and their some fastnesses. Tarım Bilimleri Dergisi 8(3):227–231
Armanini D, Fiore C, Mattarello MJ, Bielenberg J, Plermo M (2002) History of the endocrine
effects of licorice. Exp Clin Endocrinol Diabetes 110:257–261
Armanini D, Bonanni G, Mattarello MJ, Fiore C, Sartorato P, Palermo M (2003) Licorice consumption
and serum testosterone in healthy man. Exp Clin Endocrinol Diabetes 111:341–343
Armanini D, Fiore C, Bielenberg J, Ragazzi E (2005) Licorice (Glycyrrhiza glabra). In: Coates P
(ed) Encyclopedia of dietary supplements. Marcel Dekker Inc., New York, pp 391–399
Asgary S, Jafari Dinani N, Madani H, Mahzoni P, Nader Gh (2007) Effect of Glycyrrhiza glabra
extract on aorta wall atherosclerotic lesion in hypercholesterolemic rabbits. Pak J Nutr 6
(4):313–317
Asha MK, Debraj D, Prashanth D, Edwin JR, Srikanth HS, Muruganantham N, Dethe SM,
Anirban B, Jaya B, Deepak M, Agarwal A (2013) In vitro anti-Helicobacter pylori activity of a
flavonoid rich extract of Glycyrrhiza glabra and its probable mechanisms of action.
J Ethnopharmacol 145:581–586
Asl NM, Hosseinzadeh H (2008) Review of pharmacological effects of Glycyrrhiza sp, and its
bioactive compounds. Phytother Res 22(6):709–724
Awandkar SP, Mendhe MS, Badukale DM, Kulkarni MB (2012) Antimicrobial action of cold
aqueous and cold ethanolic root extracts of Glycyrrhiza glabra against bovine mammary
pathogens. Anim Sci Rep 6:88–91
Badr AE, Omar N, Badria FA (2011) A laboratory evaluation of the antibacterial and cytotoxic
effect of Liquorice when used as root canal medicament. Int Endod J 44:51–58
Baltina LA Jr, Chistoedova ES, Baltina LA, Kondratenko RM, Plyasunova OA (2012) Synthesis
and anti-HIV-1 activity of new conjugates of 18b-and 18a-glycyrrhizic acids with aspartic acid
esters. Chem Nat Compd 48:262–266
Batanouny KH, Aboutabl E, Shabana M, Soliman F (1999) Wild medicinal plants in Egypt (with
contribution of: Aboutabl E, Shabana M, Soliman F). Chapter Two—“Pharmacopoeial Wild
Medicinal Plants in Egypt” With support of the Swiss Development Co-operation (SDC).
Academy of Scientific Research and Technology, Egypt. The World Conservation Union
(IUCN), Switzerland, pp 60–64
Baytop T (1952) Anadolu meyankökü ve meyanbalı üzerinde farmakognostik araştırmalar.
Doçentlik Tezi Ist Univ Ecz Fak, Istanbul-Turkiye
Bennett A, Clark-Wibberley T, Stamford IF, Wright JE (1980) Aspirin-induced gastric mucosal
damage in rats: cimetidine and deglycyrrhizinated liquorice together give greater protection
than low doses of either drug alone. J Pharmacy Pharmacol 32:151
Bhattacharjee S, Bhattacharjee A, Majumder S, Majumdar SB, Majumdar S (2012) Glycyrrhizic
acid suppresses Cox-2-mediated anti-inflammatory responses during Leishmania donovani
infection. J Antimicrob Chemother 67:1905–1914
110 8 Economic Importance

Bielecka-Dabrowa A, Mikhailidis DP, Jones L, Rysz J, Aronow WS, Banach M (2012) The
meaning of hypokalemia in heart failure. Int J Cardiol 158:12–17
Biondi DM, Rocco C, Ruberto G (2005) Dihydrostilbene derivatives from Glycyrrhiza glabra
leaves. J Nat Prod 68:1099–1102
Blumenthal M, Goldberg A, Brinckmann J (2000) Herbal medicine: expanded commission E
monographs. Integrative Medicine Communications, Newton, MA
Bodet C, La VD, Gafner S, Bergeron C, Grenier D (2008) A licorice extract reduces
lipopolysaccharide-induced proinflammatory cytokine secretion by macrophages and whole
blood. J Periodontol 79:1752–1761
Booth CM, Matukas LM, Tomlinson GA, Rachlis AR, Rose DB, Dwosh HA, Walmsley SL,
Mazzulli T, Avendano M, Derkach P et al (2003) Clinical features and short-term outcomes of
144 patients with SARS in the greater Toronto area. JAMA 289:2801–2809
Boucher BA, Cotterchio M, Curca IA, Kreiger N, Harris SA, Kirsh VA, Goodwin PJ (2012) Intake
of phytoestrogen foods and supplements among women recently diagnosed with breast cancer
in Ontario. Canada Nutr Cancer 64:695–703
Bresch H, Urbanek M, Nusser M (2000) Ochratoxin A in food containing liquorice. Nahrung
44:276–278
Brinker F (1997) Herb contradictions and drug interactions. Eclectic Medical Publications, Sandy,
Portland, OR
Burgess JA, van der Ven PF, Martin M, Sherman J, Haley J (2008) Review of over-the-counter
treatments for aphthous ulceration and results from use of a dissolving oral patch containing
glycyrrhiza complex herbal extract. J Contemp Dent Pract 9:88–98
Cairns-Fuller V, Aldred D, Magan N (2005) Water, temperature and gas composition interactions
affect growth and ochratoxin A production by isolates of Penicillium verrucosum on wheat
grain. J Appl Microbiol 99:1215–1221
Callender VD, St. Surin-Lord S, Davis EC, Maclin M (2011) Postinflammatory hyperpigmen-
tation: etiologic and therapeutic considerations. Am J Clin Dermatol 12:87–99
Carmines EL, Lemus R, Gaworski CL (2005) Toxicologic evaluation of licorice extract as a
cigarette ingredient. Food Chem Toxicol 43:1303–1322
Cavallari LH, Limdi NA (2009) Warfarin pharmacogenomics. Curr Opin Mol Ther 11:243–251
Chakravarthi KK, Avadhani R (2013) Beneficial effect of aqueous root extract of Glycyrrhiza
glabra on learning and memory using different behavioral models: an experimental study.
J Nat Sci Biol Med 4:420–425
Chakravarthi KK, Avadhani R (2014) Enhancement of hippocampal CA3 neuronal dendritic
arborization by Glycyrrhiza glabra root extract treatment in Wistar albino rats. J Nat Sci Biol
Med 5:25–29
Chakravarthi KK, Vadhani RA, Narayan RS (2012) Effect of Glycyrrhiza glabra root extract on
learning and memory in Wistar albino rats. Int J Biol Med Res 3(3):2059–2064
Chandrasekaran CV, Sundarajan K, Gupta A, Srikanth HS, Edwin J, Agarwal A (2011) Evaluation
of the genotoxic potential of standardized extract of Glycyrrhiza glabra (GutGard). Regul
Toxicol Pharmacol 61:373–380
Cheel J, Tůmová L, Areche C, Van Antwerpen P, Nève J, Zouaoui-Boudjeltia K, San Martin A,
Vokřál I, Wsól V, Neugebauerová J (2013) Variations in the chemical profile and biological
activities of licorice (Glycyrrhiza glabra L.), as influenced by harvest times. Acta Physiol Plant
35:1337–1349
Chen F, Chan KH, Jiang Y, Kao RYT, Lu HT, Fan KW, Cheng VCC, Tsui WHW, Hung IFN,
Lee TSW, Guan Y, Peiris JSM, Yuen KY (2004) In vitro susceptibility of 10 clinical isolates of
SARS coronavirus to selected antiviral compounds. J Clin Virol 31:69–75
Chen G, Zhu L, Liu Y, Zhou Q, Chen H, Yang J (2009) Isoliquiritigenin, a flavonoid from licorice,
plays a dual role in regulating gastrointestinal motility in vitro and in vivo. Phytotherapy
Research 23(4):498–506
Chen AJ, Huang LF, Wang LZ, Tang D, Cai Fb, Gao WW (2011) Occurrence of toxigenic fungi in
ochratoxin A contaminated liquorice root. Food Addit Contam A 28(8):1091–1097
References 111

Chen AJ, Tang D, Zhou YQ, Sun BD, Li XJ, Wang LZ, Gao WW (2013) Identification of
ochratoxin A producing fungi associated with fresh and dry liquorice. PLoS ONE 8:1–13
Chen HJ, Kang SP, Lee IJ, Lin YL (2014a) Glycyrrhetinic acid suppressed NF-kappa B activation
in TNF-alpha-induced hepatocytes. J Agric Food Chem 62:618–625
Chen KJ, Chen WY, Chen X, Jia YM, Peng GQ, Chen L (2014b) Increased elimination of
paclitaxel by magnesium isoglycyrrhizinate in epithelial ovarian cancer patients treated with
paclitaxel plus cisplatin: a pilot clinical study. Eur J Drug Metab Pharmacokinet 39:25–31
Cho YC, Lee SH, Yoon G, Kim HS, Na JY, Choi HJ, Cho CW, Cheon SH, Kang BY (2010)
Licochalcone E reduces chronic allergic contact dermatitis and inhibits IL-12p40 production
through down-regulation of NF-kappa B. Int Immunopharmacol 10:1119–1126
Choi JH, Choi JN, Lee SY, Lee SJ, Kim K, Kim YK (2010) Inhibitory activity of diacylglycerol
acyltransferase by glabrol isolated from the roots of licorice. Arch Pharm Res 33:237–242
Choi JS, Han JY, Ahn HK, Ryu HM, Kim MY, Chung JH, Nava-Ocampo AA, Koren G (2013)
Fetal and neonatal outcomes in women reporting ingestion of licorice (Glycyrrhiza uralensis)
during pregnancy. Planta Med 79:97–101
Choi AY, Choi JH, Hwang KY, Jeong YJ, Choe W, Yoon KS, Ha J, Kim SS, Youn JH, Yeo EJ,
Kang I (2014) Licochalcone A induces apoptosis through endoplasmic reticulum stress via a
phospholipase C gamma1-, Ca(2+)-, and reactive oxygen species-dependent pathway in
HepG2 human hepatocellular carcinoma cells. Apoptosis 19:682–697
Chu X, Jiang L, Wei M, Yang X, Guan M, Xie X, Wei J, Liu D, Wang D (2013) Attenuation of
allergic airway inflammation in a murine model of asthma by Licochalcone A.
Immunopharmacol Immunotoxicol 35:653–661
Chueh FS, Hsiao YT, Chang SJ, Wu PP, Yang JS, Lin JJ, Chung JG, Lai TY (2012) Glycyrrhizic
acid induces apoptosis in WEHI-3 mouse leukemia cells through the caspase- and
mitochondria-dependent pathways. Oncol Rep 28:2069–2076
Cinatl J, Morgenstern B, Bauer G, Chandra P, Rabenau H, Doerr HW (2003) Glycyrrhizin, an
active component of liquorice roots, and replication of SARS-associated coronavirus. Lancet
361:2045–2046
Cirillo G, Curcio M, Parisi OI, Puoci F, Iemma F, Spizzirri UG, Restuccia D, Picci N (2011)
Molecularly imprinted polymers for the selective extraction of glycyrrhizic acid from liquorice
roots. Food Chem 125:1058–1063
Commission Regulation (EU). No. 105/2010 of 5 February 2010 amending Regulation
(EC) No. 1881/2006 setting maximum levels for certain contaminants in foodstuffs as regards
ochratoxin A. Off J Eur Union 6 February 2010
Crance JM, Biziagos E, Passagot J, van Cuyck-Gandre H, Deloince R (1990) Inhibition of
hepatitis A virus replication in vitro by antiviral compounds. J Med Virol 31:155–160
Crance JM, Scaramozzino N, Jouan A, Garin D (2003) Interferon, ribavirin, 6-azarridine and
glycyrrhizin: antiviral compounds active against pathogenic flavi viruses. Antiviral Res 58:73–79
Cui YM, Ao MZ, Li W, Yu LJ (2008) Effect of glabridin from Glycyrrhiza glabra on learning and
memory in mice. Planta Med 74:377–380
Curreli F, Friedman K, Alvin E, Flore O (2007) Protective mechanism of glycyrrhizin on acute
liver injury induced by carbon tetrachloride in mice. Biol Pharm Bull 30(10):1898–1904
Da Nagao Y, Sata M, Suzuki H, Tanikawa K, Itoh K, Kameyama T (1996) Effectiveness of
glycyrrhizin for oral lichen planus in patients with chronic HCV infection. J Gastroenterol
31:691–695
Dai XH, Li HE, Lu CJ, Wang JF, Dong J, Wei JY, Zhang Y, Wang X, Tan W, Deng XM,
Zhao SH, Zhang MJ (2013) Liquiritigenin prevents Staphylococcus aureus-mediated lung cell
injury via inhibiting the production of alpha-hemolysin. J Asian Nat Prod Res 15:390–399
Das SK, Das V, Gulati AK, Singh VP (1989) Deglycyrrhizinated liquorice in aphthous ulcers.
J Assoc Phys India 37:647
Davis EA, Morris DJ (1991) Medicinal uses of licorice through the millennia: the good and plenty
of it. Mol Cell Endocrinol 78(1):1–6
De Klerk GJ, Nieuwenhuis MG, Beutle JJ (1997) Hypokalaemia and hypertension associated with
use of liquorice flavoured chewing gum. Br Med J 314:731–732
112 8 Economic Importance

De Smet PAGM, Keller K, Hansel R, Chandler RF (1997) Adverse effects of herbal drugs, vol 2–
3. Springer-Verlag, Berlin
Dhingra D, Sharma A (2005) Evaluation of antidepressant-like activity of glycyrrhizin in mice.
Indian J Pharmacol 37:390–394
Dhingra D, Sharma A (2006) Antidepressant-like activity of Glycyrrhiza glabra L. in mouse
models of immobility tests. Prog Neuro-Psychopharmacol Biol Psychiatry 30:449–454
Dong S, Inoue A, Zhu Y, Tanji M, Kiyama R (2007) Activation of rapid signaling pathways and
the subsequent transcriptional regulation of breast cancer MCF-7 by the treatment with an
extract of Glycyrrhiza glabra root. Food Chem Toxicol 45:2470–2478
Dubey NK, Kumar A, Singh P, Shukla R (2008) Microbial contamination of raw materials: a
major reason for the decline of India’s share in the global herbal market. Curr Sci 95:717–718
Fatima A, Gupta VK, Luqman S, Negi AS, Kumar JK, Shanker K, Saikia D, Srivastava S,
Darokar MP, Khanuja SP (2009) Antifungal activity of Glycyrrhiza glabra extracts and its
active constituent glabridin. Phytother Res 23:1190–1193
Feng L, Zhu MM, Zhang MH, Wang RS, Tan XB, Song J, Ding SM, Jia XB, Hu SY (2013)
Protection of glycyrrhizic acid against AGEs-induced endothelial dysfunction through
inhibiting RAGE/NF-kappaB pathway activation in human umbilical vein endothelial cells.
J Ethnopharmacol 148:27–36
Fiore C, Eisenhut M, Krausse R, Ragazzi E, Pellati D, Armanini D, Bielenberg J (2008) Antiviral
effects of Glycyrrhiza species. Phytother Res 22:141–148
Fontes LB, Dos Santos Dias D, de Carvalho LS, Mesquita HL, da Silva Reis L, Dias AT, Da Silva
Filho A, do Amaral Correa J (2014) Immunomodulatory effects of licochalcone A on
experimental autoimmune encephalomyelitis. J Pharm Pharmacol 66:886–894
Franceschelli S, Pesce M, Vinciguerra I, Ferrone A, Riccioni G, Antonia P et al (2011)
Licocalchone-C extracted from Glycyrrhiza glabra inhibits lipopolysaccharide-interferon-c
inflammation by improving antioxidant conditions and regulating inducible nitric oxide
synthase expression. Molecules 16(7):5720–5734
Fu Y, Chen J, Li YJ, Zheng YF, Li P (2013) Antioxidant and anti-inflammatory activities of six
flavonoids separated from licorice. Food Chem 141:1063–1071
Fu Y, Zhou E, Wei Z, Liang D, Wang W, Wang T, Guo M, Zhang N, Yang Z (2014) Glycyrrhizin
inhibits the inflammatory response in mouse mammary epithelial cells and a mouse mastitis
model. FEBS J 281:2543–2557
Fuhr L, Rousseau M, Plauth A, Schroeder FC, Sauer S (2015) Amorfrutins are natural PPARc
agonists with potent antiinflammatory properties. J Nat Prod 78:1160–1164
Fujisawa Y, Sakamoto M, Matsushita M, Fujita T, Nishioka K (2000) Glycyrrhizin inhibits the
lytic pathway of complement-possible mechanism of its anti-inflammatory effect on liver cells
in viral hepatitis. Microbiol Immunol 44:799–804
Fukai T, Ali M, Kaitou K, Kanda T, Terada S, Nomura T (2002) Anti-Helicobacter pylori
flavonoids from licorice extract. Life Sci 71:1449–1463
Furuhashi I, Iwata S, Shibata S, Sato T, Inoue H (2005) Inhibition by licochalcone A, a novel
flavonoid isolated from liquorice root, of IL-1b-induced PGE2 production in human skin
fibroblasts. J Pharm Pharmacol 57:1661–1666
Furusawa J, Funakoshi-Tago M, Mashino T, Tago K, Inoue H, Sonoda Y, Kasahara T (2009)
Glycyrrhiza inflata-derived chalcones, Licochalcone A, Licochalcone B and Licochalcone D, inhibit
phosphorylation of NF-kappaB p65 in LPS signaling pathway. Int Immunopharmacol 9:499–507
Gafner S, Bergeron C, Villinski JR, Godejohann M, Kessler P, Cardellina JH, Ferreira D,
Feghali K, Grenier D (2011) Isoflavonoids and coumarins from Glycyrrhiza uralensis:
antibacterial activity against oral pathogens and conversion of isoflavans into
isoflavan-quinones during purification. J Nat Prod 74:2514–2519
Gagnon B, Robitaille R, Simard RR (1999) Characterization of several on-farm and industrial
composted materials. Can J Soil Sci 79(1):201–210
Gareri P, Condorelli D, Belluardo N, Russo E, Loiacono A, Barresi V, Trovato-Salinaro A,
Mirone MB, Ferreri Ibbadu G, De Sarro G (2004) Anticonvulsant effects of carbenoxolone in
genetically epilepsy prone rats (GEPRs). Neuropharmacology 47(8):1205–1216
References 113

Gaur R, Yadav KS, Verma RK, Yadav NP, Bhakuni RS (2014) In vivo anti-diabetic activity of
derivatives of isoliquiritigenin and liquiritigenin. Phytomedicine 21:415–422
Gaur R, Gupta VK, Singh P, Pal A, Darokar MP, Bhakuni RS (2016) Drug resistance reversal
potential of isoliquiritigenin and liquiritigenin isolated from Glycyrrhiza glabra against
methicillin-resistant Staphylococcus aureus (MRSA). Phytother Res 30:1708–1715
Ghahraman A (1999) Basic botany: anatomy and morphology, vol 1. University of Tehran Press,
pp 539
Guengerich FP (2008) Cytochrome p450 and chemical toxicology. Chem Res Toxicol 21:70–83
Güneş G (2004) Osmanlı Devleti’nde meyan kökü tarımı ve ticareti (1840–1922). Kebikeç
18:343–361
Guo XL, Liang B, Wang XW, Fan FG, Jin J, Lan R, Yang JH, Wang XC, Jin L, Cao Q (2013)
Glycyrrhizic acid attenuates CCl(4)-induced hepatocyte apoptosis in rats via a p53-mediated
pathway. World J Gastroenterol 19:3781–3791
Gupta VK, Fatima A, Faridi U, Negi AS, Shanker K, Kumar JK, Rahuja N, Luqman S,
Sisodia BS, Saikia DS, Darokar MP, Khanuja SPS (2008) Antimicrobial potential of
Glycyrrhiza glabra roots. J Ethnopharm 116:377–380
Hadar Y, Mandelbaum R (1986) Suppression of Pythium aphanidermatum damping off in
container media containing composted liquorice roots. Crop Protection 5:88–92
Hajirahimkhan A, Simmler C, Yuan Y, Anderson JR, Chen SN, Nikolic D, Dietz BM, Pauli GF,
van Breemen RB, Bolton JL (2013) Evaluation of estrogenic activity of licorice species in
comparison with hops used in botanicals for menopausal symptoms. PLoS ONE 8:e67947
Hajirahimkhan A, Simmler C, Dong H, Lantvit DD, Li G, Chen SN, Nikolic D, Pauli GF, van
Bremen RB, Dietz BM, Bolton JL (2015) Induction of NAD(P)H: quinone oxidoreductase 1
(NQO1) by Glycyrrhiza species used for women’s health: differential effects of the Michael
acceptors isoliquiritigenin and licochalcone A. Chem Res Toxicol 28(11):2130–2141
Haraguchi H, Yoshida N, Ishikawa H, Tamura Y, Mizutani K, Kinoshita T (2000) Protection of
mitochondrial functions against oxidative stresses by isoflavans from Glycyrrhiza glabra.
J Pharm Pharmacol 52:219–223
Harahap IS, Sasaki N, Gunadi Yusoff S, Lee MJ, Morikawa S, Nishimura N, Sasaki T, Usuki S,
Hirai M, Ohta M, Takaoka Y, Nishimoto T, Nishio H (2011) Herbal medicine containing
licorice may be contraindicated for a patient with an HSD11B2 mutation. Evid Based
Complement Altern Med 2011:646540
Hardy ME, Hendricks JM, Paulson JM, Faunce NR (2012a) 18 beta-glycyrrhetinic acid inhibits
rotavirus replication in culture. Virol J 9:96
Hardy RS, Raza K, Cooper MS (2012b) Endogenous glucocorticoids in inflammation:
contributions of systemic and local responses. Swiss Med Wkly 142:w13650
Hasan S, Khan R, Ali N, Khan A, Rehman M, Tahir M, Lateef A, Nafees S, Mehdi S, Rashid S,
Shahid A, Sultana S (2014) 18-beta Glycyrrhetinic acid alleviates 2-acetylaminofluorene-induced
hepatotoxicity in Wistar rats: role in hyperproliferation, inflammation and oxidative stress. Hum Exp
Toxicol. https://doi.org/10.1177/0960327114554045
Hasanein P (2011) Glabridin as a major active isoflavan from Glycyrrhiza glabra (licorice)
reverses learning and memory deficits in diabetic rats. Acta Physiol Hung 98:221–230
Hatano T, Shintani Y, Aga Y, Shiota S, Tsuchiya T, Yoshida T (2000) Phenolic constituents of
licorice. VIII. Structures of glicophenone and glicoisoflavanone, and effects of licorice
phenolics on methicillin resistant Staphylococcus aureus. Chem Pharm Bull 48:1286–1292
Hattori T, Ikematsu S, Koito A, Matsushita S, Maeda Y, Hada M, Fujimaki M, Takatsuki K (1989)
Preliminary evidence for inhibitory effect of glycyrrhizin on HIV replication in patients with
AIDS. Antiviral Res 11:255–261
Hayashi H, Sudo H (2009) Economic importance of licorice. Plant Biotechnol 26:101–104
He J, Chen L, Heber D, Shi W, Lu Q-Y (2006) Antibacterial compounds from Glycyrrhiza
uralensis. J Nat Prod 69:121–124
He Y, Zeng F, Liu Q, Ju W, Fu H, Hao H, Li L, Xie Y (2010) Protective effect of magnesium
isoglycyrrhizinate on ethanol-induced testicular injuries in mice. J Biomed Res 24:153–160
114 8 Economic Importance

Hendricks JM, Hoffman C, Pascual DW, Hardy ME (2012) 18 beta-glycyrrhetinic acid delivered
orally induces isolated lymphoid follicle maturation at the intestinal mucosa and attenuates
rotavirus shedding. PLoS ONE 7:e49491
Herrera M, Herrera A, Ariño A (2009) Estimation of dietary intake of ochratoxin A from liquorice
confectionery. Food Chem Toxicol 47:2002–2006
Hesham RE, Shgeru N (2002) Chemistry of bioflavonoids. Indian J Pharm Educ 36:191–194
Hojo H, Sato J (2002) Antifungal activity of licorice (Glycyrrhiza glabra) and potential
applications in beverage. Foods Food Ingredients J Jpn 203:27–33
Hong ND, Koo BH, Joo SM, Lee SK (1988) Studies on the efficacy of combined preparation of
crude drugs. Effects of sipmidojuksan on the central nervous and cardiovascular systems.
Korean J Pharmacol 19(2):141
Hong YK, Wu HT, Ma T, Liu WJ, He XJ (2009) Effects of Glycyrrhiza glabra polysaccharides on
immune and antioxidant activities in high-fat mice. Int J Biol Macromol 45:61–64
Hossain MS, Hossain MA, Islam R, Alam AH, Zahan K, Sarkar S, Farooque MA (2004)
Antimicrobial and cytotoxic activities of 2-aminobenzoic acid and 2-aminophenol and their
coordination complexes with Magnesium (Mg- II). Pak J Biol Sci 7:25–27
Houseman PA (1944) In licorice-putting a weed to work, pp 3. 10–15, The Royal Institute of
Chemistry of Great Britain and Ireland, London
Hsu YL, Kuo PL, Chiang LC, Lin CC (2004) Isoliquiritigenin inhibits the proliferation and
induces the apoptosis of human non-small cell lung cancer A549 cells. Clin Exp Pharmacol
Physiol 31(7):414–418
Hsu YL, Wu LY, Hou MF, Tsai EM, Lee JN, Liang HL, Jong YJ, Hung CH, Kuo PL (2011)
Glabridin, an isoflavan from licorice root, inhibits migration, invasion and angiogenesis of
MDA-MB-231 human breast adenocarcinoma cells by inhibiting focal adhesion kinase/Rho
signaling pathway. Mol Nutr Food Res 55:318–327
Hu CH, He J, Eckert R, Wu XY, Li LN, Tian Y, Lux R, Shuffer JA, Gelman F, Mentes J,
Spackman S, Bauer J, Anderson MH, Shi WY (2011) Development and evaluation of a safe
and effective sugar-free herbal lollipop that kills cavity-causing bacteria. Int J Oral Sci 3:13–20
Huang W, Chen X, Li Q, Li P, Zhao G, Xu M, Xie P (2012) Inhibition of intercellular adhesion in
herpex simplex virus infection by glycyrrhizin. Cell Biochem Biophys 62:137–140
Huang W, Tang S, Qiao X, Ma W, Ji S, Wang K, Ye M, Yu S (2014a) Isoangustone A induces
apoptosis in SW480 human colorectal adenocarcinoma cells by disrupting mitochondrial
functions. Fitoterapia 94:36–47
Huang X, Qin J, Lu S (2014b) Magnesium isoglycyrrhizinate protects hepatic L02 cells from
ischemia/reperfusion induced injury. Int J Clin Exp Pathol 7:4755–4764
Huo HZ, Wang B, Liang YK, Bao YY, Gu Y (2011) Hepatoprotective and antioxidant effects of
licorice extract against CCl(4)-induced oxidative damage in rats. Int J Mol Sci 12:6529–6543
İlisulu K (1974) Meyankökü çeşitleri, özellikleri, adaptasyonu ve ziraatte faydalabilme olanakları
hakkında araştırmalar. AU Zir. Fak. Yıllığı, 96
İlisulu K, Kolsarıcı O (1986) Natural growing areas of the liquorice (Glycyrrhiza glabra L.) and
the possibilities its cultivation. İlaç Hammaddeleri Toplantısı (16–18 Mayıs 1986). Gazi
Üniversitesi Yayınları No: 113, pp 171–182
Imai K, Takagi Y, Iwazaki A, Nakanishi K (2013) Radical scavenging ability of glycyrrhizin. Free
Radic Antioxid 3:40–42
Irani M, Sarmadi M, Bernard F, Ebrahim GH, Bazarnov HS (2010) Leaves antimicrobial activity
of Glycyrrhiza glabra L. Iran J Pharm Res 9(4):425–428
Isbrucker RA, Burdock GA (2006) Risk and safety assessment on the consumption of Licorice
root (Glycyrrhiza sp.), its extract and powder as a food ingredient, with emphasis on the
pharmacology and toxicology of glycyrrhizin. Regul Toxicol Pharmacol 46(3):167–192
Ishida T, Miki I, Tanahashi T, Yagi S, Kondo Y, Inoue J, Kawauchi S, Nishiumi S, Yoshida M,
Maeda H, Tode C, Takeuchi A, Nakayama H, Azuma T, Mizuno S (2013) Effect of
18beta-glycyrrhetinic acid and hydroxypropyl gammacyclodextrin complex on
indomethacin-induced small intestinal injury in mice. Eur J Pharmacol 714:125–131
References 115

Jain E, Pandey RK, Khanna R (2013) Liquorice root extracts as potent cariostatic agents in
pediatric practice. J Indian Soc Pedod Prev Dent 31:146–152
Jeong HG, You HJ, Park SJ, Moon AR, Chung YC, Kang SK, Chun HK (2002) Hepatoprotective
effects of 18b-glycyrrhetinic acid on carbon tetrachloride-induced liver injury: inhibition of
cytochrome P450 2E1 expression. Pharm Res 46:221–227
Jhanji V, Liu H, Law K, Lee VY, Huang SF, Pang CP, Yam GH (2011) Isoliquiritigenin from
licorice root suppressed neovascularisation in experimental ocular angiogenesis models. Br J
Ophthalmol 95:1309–1315
Jiang J, Yuan X, Zhao H, Yan X, Sun X, Zheng Q (2014) Licochalcone A inhibiting proliferation
of bladder cancer T24 cells by inducing reactive oxygen species production. Biomed Mater
Eng 24:1019–1025
Jo EH, Kim SH, Ra JC, Kim SR, Cho SD, Jung JW, Yang SR, Park JS, Hwang JW, Aruoma OI,
Kim TY, Lee YS, Kang KS (2005) Chemopreventive properties of the ethanol extract of
Chinese licorice (Glycyrrhiza uralensis) root: induction of apoptosis and G1 cell cycle arrest in
MCF-7 human breast cancer cells. Cancer Lett 230:239–247
Jung W, Kwon S, Im J, Park S, Moon S, Park J, Ko C, Cho K (2014) Influence of herbal
complexes containing licorice on potassium levels: a retrospective study. Evid Based
Complement Altern Med 2014:970385
Kabelitz L, Sievers H (2004) Contaminants of medicinal and food herbs with a view to EU
regulations. Innov Food Technol 2004:25–27
Kakegawa H, Matsumoto H, Satoh T (1992) Inhibitory effects of some natural products on the
activation of hyaluronidase and their anti-allergic actions. Chem Pharm Bull 40:1439–1442
Kamalak A (2006) Determination of nutritive value of leaves of a native grown shrub, Glycyrrhiza
glabra L. using in vitro and in situ measurements. Small Ruminant Res 64:268–278
Kanazawa M, Satomi Y, Mizutani Y, Ukimura O, Kawauchi A, Sakai T, Baba M, Okuyama T,
Nishino H, Miki T (2003) Isoliquiritigenin inhibits the growth of prostate cancer. Eur Urol
43:580–586
Kang H, Lieberman PM (2011) Mechanism of glycyrrhizic acid inhibition of Kaposiʼs
sarcoma-associated herpesvirus: disruption of CTCF-cohesin mediated RNA polymerase II
pausing and sister chromatid cohesion. J Virol 85:11159–11169
Kang JS, Yoon YD, Cho IJ, Han MH, Lee CW, Park SK, Kim HM (2005) Glabridin, an isoflavan
from licorice root, inhibits inducible nitric-oxide synthase expression and improves survival of
mice in experimental model of septic shock. J Pharmacol Exp Ther 312:1187–1194
Kao T-C, Wu C-H, Yen G-C (2014) Bioactivity and potential health benefits of licorice. J Agric
Food Chem 62:542–553
Kapetanakou AE, Panagou EZ, Gialitaki M, Drosinos EH, Skandamis PN (2009) Evaluating the
combined effect of water activity, pH and temperature on ochratoxin A production by
Aspergillus ochraceus and Aspergillus carbonarius on culture medium and Corinth raisins.
Food Control 20:725–732
Karahan F, Avsar C, Ozyigit II, Berber I (2016) Antimicrobial and antioxidant activities of
medicinal plant Glycyrrhiza glabra var. glandulifera from different habitats. Biotechnol
Biotechnol Equip. https://doi.org/10.1080/13102818.2016.1179590
Kataya HH, Hamza AA, Ramadan GA, Khasawneh MA (2011) Effect of licorice extract on the
complications of diabetes nephropathy in rats. Drug Chem Toxicol 34:101–108
Kent UM, Aviram M, Rosenblat M, Hollenberg PF (2002) The licorice root derived isoflavan
glabridin inhibits the activities of human cytochrome P450S 3A4, 2B6, and 2C9. Drug Metab
Dispos 30:709–715
Khalesi M (2015) Ochratoxin A in liquorice products—a review. Food Additives & Contaminants:
Part A. https://doi.org/10.1080/19440049.2015.1094708
Khalesi M, Khatib N (2011) The effects of different ecophysiological factors on ochratoxin A
production. Environ Toxicol Phar 32:113–121
Khalesi M, Sheikh-Zeinoddin M, Tabrizchi M (2011) Determination of ochratoxin A in licorice
root using inverse ion mobility spectrometry. Talanta 83:988–993
116 8 Economic Importance

Khalesi M, Tabrizchi M, Sheikh-Zeinoddin M (2013) The effects of temperature and relative

humidity on ochratoxin A formation in fresh liquorice root. Food Addit Contam A 30:339–344
Khan R, Khan AQ, Lateef A, Rehman MU, Tahir M, Ali F, Hamiza OO, Sultana S (2013)
Glycyrrhizic acid suppresses the development of precancerous lesions via regulating the
hyperproliferation, inflammation, angiogenesis and apoptosis in the colon of Wistar rats.
PLoS ONE 8:e56020
Kim YJ, Uyama H (2005) Tyrosinase inhibitors from natural and synthetic sources: structure,
inhibition mechanism and perspective for the future. Cell Mol Life Sci 62:1707–1723
Kim KR, Jeong CK, Park KK, Choi JH, Park JH, Lim SS, Chung WY (2010) Anti-inflammatory
effects of licorice and roasted licorice extracts on TPA-induced acute inflammation and
collagen induced arthritis in mice. J Biomed Biotechnol (709378)
Kim HJ, Lim SS, Park IS, Lim JS, Seo JY, Kim JS (2012) Neuroprotective effects of
dehydroglyasperin C through activation of heme oxygenase-1 in mouse hippocampal cells.
J Agric Food Chem 60:5583–5589
Kim J, Joo I, Kim H, Han Y (2013a) 18beta-glycyrrhetinic acid induces immunological adjuvant
activity of Th1 against Candida albicans surface mannan extract. Phytomedicine 20:951–955
Kim J, Kim J, Shim J, Lee S, Kim J, Lim SS, Lee KW, Lee HJ (2013b) Licorice-derived
dehydroglyasperin C increases MKP-1 expression and suppresses inflammation-mediated
neurodegeneration. Neurochem Int 63:732–740
Kim ME, Kim HK, Kim DH, Yoon JH, Lee JS (2013c) 18beta-Glycyrrhetinic acid from licorice
root impairs dendritic cells maturation and Th1 immune responses. Immunopharmacol
Immunotoxicol 35:329–335
Kim KJ, Choi JS, Kim KW, Jeong JW (2013d) The anti-angiogenic activities of glycyrrhizic acid
in tumor progression. Phytother Res 27:841–846
Kim JS, Park MR, Lee SY, Kim DK, Moon SM, Kim CS, Cho SS, Yoon G, Im HJ, You JS,
Oh JS, Kim SG (2014) Licochalcone A induces apoptosis in KB human oral cancer cells via a
caspase-dependent FasL signaling pathway. Oncol Rep 31:755–762
Kırmızıbekmez H, Uysal GB, Masullo M, Demirci F, Bağcı Y, Kan Y, Piacente S (2015)
Prenylated polyphenolic compounds from Glycyrrhiza iconica and their antimicrobial and
antioxidant activities. Fitoterapia 103:289–293
Kong ND, Chang IK, Lee SI, Kim NJ (1984) Studies on the efficacy of combined preparation of
crude drugs: Effects of “Bojungikgi-tang” on the digestive system, blood pressure and diuretic
actions. Korean J. Pharmacog. 15(3):121–127
Kratschmar DV, Vuorinen A, Da Cunha T, Wolber G, Classen-Houben D, Doblhoff O,
Schuster D, Odermatt A (2011) Characterization of activity and binding mode of glycyrrhetinic
acid derivatives inhibiting 11beta-hydroxysteroid dehydrogenase type 2. J Steroid Biochem
Mol Biol 125:129–142
Kuo KK, Chang JS, Wang KC, Chiang LC (2009) Water extract of Glycyrrhiza uralensis inhibited
enterovirus 71 in a human foreskin fibroblast cell line. Am J Chin Med 37(2):383–394
Kuramoto T, Ito Y, Oda M, Tamura Y, Kitahara S (1994) Microbial production of glycyrrhetic
acid 3-O-mono-b-D-glucuronide from glycyrrhizin by Cryptococcus magnus MG-27. Biosci
Biotechnol Biochem 58:455–458
Kwon HS, Oh SM, Kim JK (2008) Glabridin, a functional compound of liquorice, attenuates
colonic inflammation in mice with dextran sulphate sodium-induced colitis. Clin Exp Immunol
151:165–173
Kwon HJ, Kim HH, Ryu YB, Kim JH, Jeong HJ, Lee SW, Chang JS, Cho KO, Rho MC, Park SJ,
Lee WS (2010) In vitro anti-rotavirus activity of polyphenol compounds isolated from the roots
of Glycyrrhiza uralensis. Bioorg Med Chem 18:7668–7674
Kwon SJ, Park SY, Kwon GT, Lee KW, Kang YH, Choi MS, Yun JW, Jeon JH, Jun JG, Park JH
(2013) Licochalcone E present in licorice suppresses lung metastasis in the 4T1 mammary
orthotopic cancermodel. Cancer Prev. Res. (Phila) 6:603–613
La VD, Tanabe S, Bergeron C, Gafner S, Grenier D (2011) Modulation of matrix metallopro-
teinase and cytokine production by licorice isolates licoricidin and licorisoflavan A: potential
therapeutic approach for periodontitis. J Periodontol 82:122–128
References 117

Lateef M, Iqba L, Fatima N, Siddiqui K, Afza N, Zia-ul-Haq M, Ahmad M (2012) Evaluation of

antioxidant and urease inhibition activities of roots of Glycyrrhiza glabra. Pak. J. Pharm. Sci.
25:99–102
Lau D, Plotkin BJ (2013) Antimicrobial and biofilm effects of herbs used in traditional Chinese
medicine. Nat Prod Commun 8:1617–1620
Lee J, Jung E, Park J, Jung K, Park J, Kim J, Hong S, Park J, Park S, Lee S, Park D (2005)
Glycyrrhizin induces melanogenesis by elevating a camp level in B16 melanoma cells. J Invest
Dermatol 124:405–411
Lee HY, Jung DY, Ha H, Kang SS, Kim JS, Kim C (2007) Induction of growth hormone release
by Glycyrrhizae Radix on rat. J Biochem Mol Biol 40:979–985
Lee JY, Lee JH, Park JH, Kim SY, Choi JY, Lee SH, Kim YS, Kang SS, Jang EC, Han Y (2009)
Liquiritigenin, a licorice flavonoid, helpsmice resist disseminated candidiasis due to Candida
albicans by Th1 immune response, whereas liquiritin, its glycoside form, does not. Int
Immunopharmacol 9:632–638
Lee YS, Kim SH, Kim JK, Shin HK, Kang YH, Park JH, Lim SS (2010) Rapid identification and
preparative isolation of antioxidant components in licorice. J Sep Sci 33:664–671
Lee HN, Cho HJ, Lim DY, Kang YH, Lee KW, Park JH (2013a) Mechanisms by which licochalcone e
exhibits potent anti-inflammatory properties: studies with phorbol ester-treated mouse skin and
lipopolysaccharide- stimulated murine macrophages. Int J Mol Sci 14:10926–10943
Lee E, Son JE, Byun S, Lee SJ, Kim YA, Liu K, Kim J, Lim SS, Park JH, Dong Z, Lee KW,
Lee HJ (2013b) CDK2 and mTOR are direct molecular targets of isoangustone A in the
suppression of human prostate cancer cell growth. Toxicol Appl Pharmacol 272:12–20
Lee SK, Park KK, Park JH, Lim SS, Chung WY (2013c) The inhibitory effect of roasted licorice
extract on human metastatic breast cancer cell-induced bone destruction. Phytother. Res.
27:1776–1783
Li J, Tu Y, Tong L, Zhang W, Zheng J, Wei Q (2010a) Immunosuppressive activity on the murine
immune responses of glycyrol from Glycyrrhiza uralensis via inhibition of calcineurin activity.
Pharm Biol 48:1177–1184
Li J, Lee YS, Choi JS, Sung HY, Kim JK, Lim SS, Kang YH (2010b) Roasted licorice extracts
dampen high glucose-induced mesangial hyperplasia and matrix deposition through blocking
Akt activation and TGF-beta signaling. Phytomedicine 17:800–810
Li X, He X, Liu B, Xu L, Lu C, Zhao H, Niu X, Chen S, Lu A (2012) Maturation of murine bone
marrow-derived dendritic cells induced by Radix Glycyrrhizae polysaccharide. Molecules
17:6557–6568
Li W, Li S, Higai K, Sasaki T, Asada Y, Ohshima S, Koike K (2013) Evaluation of licorice flavonoids
as protein tyrosine phosphatase 1B inhibitors. Bioorg Med Chem Lett 23:5836–5839
Li JY, Cao HY, Liu P, Cheng GH, Sun MY (2014) Glycyrrhizic acid in the treatment of liver
diseases: literature review. Biomed Res Int 2014:872139
Lin D, Zhong W, Li J, Zhang B, Song G, Hu T (2014) Involvement of BID translocation in
glycyrrhetinic acid and 11-deoxy glycyrrhetinic acid-induced attenuation of gastric cancer
growth. Nutr Cancer 66:463–473
Liu W, Kato M, Akhand A, Hayakawa A, Takemura M, Yoshida S, Suzuki H, Nakashima I (1998)
The herbal medicine Sho-saiko-to inhibits the growth of malignant melanoma cells by
up-regulating Fas mediated apoptosis and arresting cell cycle through down regulation of
cyclin dependent kinases. Int J Oncol 12:1321–1326
Liu HM, Sugimoto N, Akiyama T, Maitani T (2000) Constituents and their sweetness of food
additive enzymatically modified licorice extract. J Agric Food Chem 48:6044–6047
Long DR, Mead J, Hendricks JM, Hardy ME, Voyich JM (2013) 18beta-Glycyrrhetinic acid
inhibits methicillin-resistant Staphylococcus aureus survival and attenuates virulence gene
expression. Antimicrob Agents Chemother 57:241–247
Lou XF, Nair J (2009) The impact of landfilling and composting on greenhouse gas emissions—A
review. Bioresource Technol. 100:3792–3798
Lucas (1976) Nature’s medicines. Melvin Powers/Wilshire Book Company, North Hollywood,
CA, pp 89–94
118 8 Economic Importance

Luo L, Jin Y, Kim ID, Lee JK (2013) Glycyrrhizin attenuates kainic Acid-induced neuronal cell
death in the mouse hippocampus. Exp. Neurobiol. 22:107–115
Ma X, Lian QQ, Dong Q, Ge RS (2011) Environmental inhibitors of 11beta-hydroxysteroid
dehydrogenase type 2. Toxicology 285:83–89
Ma C, Ma Z, Liao XL, Liu J, Fu Q, Ma S (2013) Immunoregulatory effects of glycyrrhizic acid exerts
anti-asthmatic effects via modulation of Th1/Th2 cytokines and enhancement of CD4(+)CD25(+)
Foxp3+ regulatory T cells in ovalbumin-sensitized mice. J Ethnopharmacol 148:755–762
Majerus P, Max M, Klaffke H, Palavinskas R (2000) Ochratoxin A in Sübholz, Lakritze und
daraus hergestellten Erzeugnissen. Deustche Lebensmittel-Rundschau. 96:451–454
Mamedov NA, Egamberdieva D (2017) Phytochemical constituents and pharmacological effects of
liquorice: a review. In: Oztürk et al (eds) Herbals and human health-phytochemistry. Springer
Nature Publishers, 41 pp
Martinez A, Ikken Y, Cambero MI, Marin ML, Haza AI, Casas C, Morales P (1999) Mutagenicity and
cytotoxicity of fruits and vegetables evaluated by the Ames test and 3-(4,5-dimethylthiazol-2-yl)-
2,5-diphenyltetrazolium bromide (MTT) assay. Food Sci Technol Int 5:431–437
Masoomeh MJ, Kiarash G (2007) In vitro susceptibility of Helicobacter pylori to licorice extract.
Iran J. Pharm. Res. 6:69–72
Matsui S, Matsumoto H, Sonoda Y, Ando K, Aizu-Yokota OT, Kasahara T (2004) Glycyrrhizin
and related compounds down-regulate production of inflammatory chemokines IL-8 and
eotaxin 1 in a human lung fibroblast cell line. Int Immunopharmacol 4(13):1633–1644
Matsumoto Y, Matsuura T, Aoyagi H, Matsuda M, Hmwe SS, Date T, Watanabe N, Watashi K,
Suzuki R, Ichinose S, Wake K, Suzuki T, Miyamura T, Wakita T, Aizaki H (2013) Antiviral
activity of glycyrrhizin against hepatitis C virus in vitro. PLoS ONE 8:e68992
McGuffin M, Hobbs C, Upton R, Goldberg A (1997) Botanical Safety Handbook. CRC Press,
Boca Raton, FL
Medina S, Krassnovsky A, Yogev A, Raviv M (2011) Horticultural characteristics of licorice
waste compost. Compost Science & Utilization 19(3):163–169
Meghashri SG (2009) In vitro antifungal and antibacterial activities of root extract of Glycyrrhiza
glabra. J. Appl. Sci. Res. 5:1436–1439
Menati L, Khaleghinezhad K, Tadayon M, Siahpoosh A (2014) Evaluation of contextual and
demographic factors on licorice effects on reducing hot flashes in postmenopause women.
Health Care Women Int 35:87–99
Messier C, Grenier D (2011) Effect of licorice compounds licochalcone A, glabridin and glycyrrhizic
acid on growth and virulence properties of Candida albicans. Mycoses 54:e801–e806
Methlie P, Husebye EE, Hustad S, Lien EA, Lovas K (2011) Grapefruit juice and licorice increase
cortisol availability in patients with Addisonʼs disease. Eur J Endocrinol 165:761–769
Michaelis M, Geiler J, Naczk P, Sithisarn P, Ogbomo H, Altenbrandt B, Leutz A, Doerr HW,
Cinatl J Jr (2010) Glycyrrhizin inhibits highly pathogenic H5N1 influenza A virus-induced
pro-inflammatory cytokine and chemokine expression in human macrophages. Med Microbiol
Immunol 199:291–297
Michel HE, Tadros MG, Abdel-Naim AB, Khalifa AE (2013) Prepulse inhibition (PPI) disrupting
effects of Glycyrrhiza glabra extract in mice: a possible role of monoamines. Neurosci Lett
544:110–114
Mishra NK, Bstia S, Mishra G, Chowdary KA, Patra S (2011) Anti-arthritic activity of Glycyrrhiza
glabra, Boswellia serrata and their synergistic activity in combined formulation studied in
freund’s adjuvant induced arthritic rats. J. Pharm. Educ. Res. 2:92–98
Mitscher LA, Drake S, Gollapudi SR, Harris JA, Shankel DM (1986) Isolation and identification
of higher plant agents active in antimutagenic assay systems: Glycyrrhiza glabra. Basic Life
Sci 39:153–165
Mizutani K, Kuramoto T, Tamura Y, Ohtake N, Doi S, Nakaura M, Tanaka O (1994) Sweetness of
glycyrrhetinic acid 3-O-mono-b-D-glucuronide and related glycosides. Biosci Biotechnol
Biochem 58:554–555
References 119

Mohseni R, Noorbakhsh F, Moazeni M, Nasrollahi Omran A, Rezaie S (2014) Antitoxin

characteristic of licorice extract: the ınhibitory effect on aflatoxin production in Aspergillus
parasiticus. J Food Saf 34(2):119–125
Moisy D, Avilov SV, Jacob Y, Laoide BM, Ge X, Baudin F, Naffakh N, Jestin JL (2012) HMGB1
protein binds to influenza virus nucleoprotein and promotes viral replication. J Virol 86:9122–9133
Mu Y, Zhang J, Zhang S, Zhou HH, Toma D, Ren S, Huang L, Yaramus M, Baum A,
Venkataramanan R, Xie W (2006) Traditional Chinese medicines Wu Wei Zi (Schisandra
chinensis Baill) and Gan Cao (Glycyrrhiza uralensis Fisch) activate pregnane X receptor and
increase warfarin clearance in rats. J Pharmacol Exp Ther 316:1369–1377
Muralidharan P, Balamurugan G, Babu V (2009) Cerebroprotective effect of Glycyrrhiza glabra
Linn. root extract on hypoxic rats. Bangladesh J. Pharmacol. 4:60–64
Nagai H, He JX, Tani T, Akao T (2007) Antispasmodic activity of licochalcone A, a
species-specific ingredient of Glycyrrhiza inflata roots. J Pharm Pharmacol 59(10):1421–1426
Nakagawa K, Hidaka T, Kitano M, Asakura M, Kamigaito T, Noguchi T, Hosoe K (2008)
Genotoxicity studies on licorice flavonoid oil (LFO). Food Chem Toxicol 46:2525–2532
Nand P, Drabu S, Gupta R (2012) Phytochemical and antimicrobial screening of medicinal plants
for the treatment of acne. Indian J. Nat. Prod. Res. 3(1):28–32
Nerya O, Vaya J, Musa R, Izrael S, Ben-Arie R, Tamir S (2003) Glabrene and isoliquiritigenin as
tyrosinase inhibitors from liquorice roots. J Agric Food Chem 51(5):1201–1207
Ni YF, Kuai JK, Lu ZF, Yang GD, Fu HY, Wang J, Tian F, Yan XL, Zhao YC, Wang YJ, Jiang T
(2011) Glycyrrhizin treatment is associated with attenuation of lipopolysaccharide-induced
acute lung injury by inhibiting cyclooxygenase-2 and inducible nitric oxide synthase
expression. J Surg Res 165:e29–e35
Nieman C (1957) Licorice. Advances in Food Research 7:339–381
Nirmala P, Selvaraj T (2011) Anti-inflammatory and anti-bacterial activities of Glycyrrhiza glabra
L. Int. J. Agric. Technol. 7:815–823
Nitalikar MM, Munde KC, Dhore BV, Shikalgar SN (2010) Studies of antibacterial activities of
Glycyrrhiza glabra root extract. International J. PharmTech Research 2(1):899–901
Nomura T, Fukai T (1998) Phenolic constituents of licorice (Glycyrrhiza species). In: Herz W
et al. (eds) Progress in the chemistry of organic natural products 73, Springer Wien-New York,
pp 1–140
Nomura T, Fukai T, Akiyama T (2002) Chemistry of phenolic compounds of licorice (Glycyrrhiza
species) and their estrogenic and cytotoxic activities. Pure Appl Chem 74:1199–1206
Olukoga A, Donaldson D (2000) Liquorice and its health implications. J. Roy. Soc. Promot.
Health 120:83–89
Orlent H, Hansen BE, Willems M, Brouwer JT, Huber R, Kullak-Ublick GA, Gerken G,
Zeuzem S, Nevens F, Tielemans WC, Zondervan PE, Lagging M, Westin J, Schalm SW (2006)
Biochemical and histological effects of 26 weeks of glycyrrhizin treatment in chronic hepatitis
C: a randomized phase II trial. J Hepatol 45:539–546
Ovez B, Ozgen S, Yuksel M (2006) Biological denitrification in drinking water using Glycyrrhiza
glabra and Arunda donax as the carbon source. Process Biochem 41:1539–1544
Özgün C (2014) Bereketli topraklarda üretmek ve paylaşmak - “İzmir ve çevresinde ticari tarım
(1844–1914). İzmir Büyükşehir Belediyesi Kent Kitaplığı, İzmir-Türkiye
Ozhan M, Gol K (1975) Meyan otunun (Glycyrrhiza sp.) kabayem olarak kullanılma olanakları.
Ataturk Universitesi Ziraat Fakultesi Ziraat Dergisi 1:1–12
Oztanir MN, Ciftci O, Cetin A, Durak MA, Basak N, Akyuva Y (2014) The beneficial effects of
18beta-glycyrrhetinic acid following oxidative and neuronal damage in brain tissue caused by
global cerebral ischemia/reperfusion in a C57BL/J6 mouse model. Neurol Sci 35:1221–1228
Pandian N, Chidambaram S (2017) Antimicrobial, cytotoxicty and anti cancer activity of silver
nanoparticles from Glycyrrhiza glabra. Int J Pharm Sci Res 8(4):1633–1641
Park I, Kim J, Lee Y, Shin S (2008) In vivo fungicidal activity of medicinal plant extracts against
six phytopathogenic fungi. Int J Pest Manage 54:63–68
120 8 Economic Importance

Park D, Yang YH, Choi EK, Yang G, Bae DK, Lee SH, Kim TK, Kyung J, Kim D, Choi KC,
Kim YB (2011) Licorice extract increases cyclophosphamide teratogenicity by upregulating
the expression of cytochrome P-450 2B mRNA. Birth Defects Res B Dev Reprod Toxicol
92:553–559
Park HG, Bak EJ, Woo GH, Kim JM, Quan Z, Kim JM, Yoon HK, Cheon SH, Yoon G, Yoo YJ,
Na Y, Cha JH (2012) Licochalcone E has an antidiabetic effect. J Nutr Biochem 23:759–767
Park SM, Lee JR, Ku SK, Cho IJ, Byun SH, Kim SC, Park SJ, Kim YW (2016) Isoliquiritigenin in
licorice functions as a hepatic protectant by induction of antioxidant genes through
extracellular signal-regulated kinase-mediated NF-E2-related factor-2 signaling pathway.
Eur J Nutr 55(8):2431–2444
Parker PM (2007) The World market for licorice roots. ICON Group Ltd., USA
Patil SM, Patil MB, Sapkale GN (2009) Antimicrobial activity of Glycyrrhiza glabra Linn. Roots
Int J Chem Sci 7(1):585–591
Pellatti D, Fiore C, Armanini D, Rassu M, Bertoloni G (2009) In vitro effects of glycyrrhetinic acid
on the growth of clinical isolates of Candida albicans. Phytother Res 23:572–574
Peters MC, Tallman JA, Braun TM, Jacobson JJ (2010) Clinical reduction of S. mutans in
pre-school children using a novel liquorice root extract lollipop: a pilot study. Eur Arch
Paediatr Dent 11:274–278
Pietri A, Rastelli S, Bertuzzi T (2010) Ochratoxin A and aflatoxins in liquorice products. Toxins
2:758–770
Plyasunova OA, Egoricheva IN, Fedyuk NV, Pokrovsky AG, Baltina LA, Murinov YI,
Tolstikov GA (1992) Vopr Virusol 37:235–238
Rahman MS, Rashid MA (2008) Antimicrobial activity and cytotoxicity of Eclipta prostrata.
Oriental Pharm Exp Med 8:47–52
Raikkonen K, Seckl JR, Heinonen K, Pyhala R, Feldt K, Jones A, Pesonen AK, Phillips DI,
Lahti J, Jarvenpaa AL, Eriksson JG, Matthews KA, Strandberg TE, Kajantie E (2010) Maternal
prenatal licorice consumption alters hypothalamic-pituitary-adrenocortical axis function in
children. Psychoneuroendocrinology 35:1587–1593
Rao KVS (1993) A review on licorice. Anc Sci Life XIII(1–2):57–88
Rasool M, Iqbal J, Malik A, Ramzan HS, Qureshi MS, Asif M, Qazi MH, Kamal MA,
Chaudhary AG, Al-Qahtani MH, Gan SH, Karim S (2014) Hepatoprotective effects of Silybum
marianum (Silymarin) and Glycyrrhiza glabra (Glycyrrhizin) in combination: a possible
synergy. Evid Based Complement Altern Med 2014:641597
Rathi SG, Suthar M, Patel P, Bhaskar VH, Rajgor NB (2009) In-vitro cytotoxic screening of
Glycyrrhiza glabra L. (Fabaceae): a natural anticancer drug. J Young Pharm 1:239–243
Rauchensteiner F, Matsumura Y, Yamamoto Y, Yamaji S, Tani T (2005) Analysis and comparison
of Radix Glycyrrhizae (licorice) from Europe and China by capillary-zone electrophoresis
(CZE). J Pharmaceut Biomed 38:594–600
Rogers M (ed) (2014) Licorice. In: Herbalpedia. http://www.herbalpedia.com
Roshan A, Verma NK, Kumar CS, Chandra V, Singh DP, Panday MK (2012) Phytochemical
constituent, pharmacological activities and medicinal uses through the millenia of Glycyrrhiza
glabra Linn: a review. Int Res J Pharm 3(8):45–55
Ruiz-Granados ES, Shouls G, Sainsbury C, Antonios T (2012) A salty cause of severe
hypertension. BMJ Case Rep 2012
Russo S, Mastropasqua M, Mosetti MA, Persegani C, Paggi A (2000) Low doses of liquorice can
induce hypertension encephalopathy. Am J Nephrol 20:145–148
Saeedi M, Morteza-Semnani K, Ghoreishi MR (2003) The treatment of atopic dermatitis with
licorice gel. J Dermatol Treat 14:153–157
Saleem MMNM, Mohammad AAW, Al-Tameemi JA, Sulaiman GM (2011) Biological study of
the effect of licorice roots extract on serum lipid profile, liver enzymes and kidney function
tests in albino mice. Afr J Biotechnol 10:12702–12706
References 121

Salvi M, Fiore C, Armanini D, Toninello A (2003) Glycyrrhetinic acid-induced permeability

transition in rat liver mitochondria. Biochem Pharmacol 66:2375–2379
Sasaki H, Takei M, Kobayashi M, Pollard RB, Suzuki F (2002) Effect of glycyrrhizin, an active
component of licorice roots, on HIV replication in cultures of peripheral blood mononuclear
cells from HIV-seropositive patients. Pathobiology 70:229–236
Sasaki H, Suzuki N, Alshwaimi E, Xu Y, Battaglino R, Morse L, Stashenko P (2010)
18beta-glycyrrhetinic acid inhibits periodontitis via glucocorticoidin dependent nuclear
factor-kappaB inactivation in interleukin-10-deficient mice. J Periodontal Res 45:757–763
Saxena S (2005) Glycyrrhiza glabra: medicine over the millennium. Nat Prod Radiance 4(5):358–
367
Sen S, Roy M, Chakraborti AS (2011) Ameliorative effects of glycyrrhizin on
streptozotocin-induced diabetes in rats. J Pharm Pharmacol 63:287–296
Seo JY, Han JH, Kim YJ, Lim SS, Kim J (2014) Protective effects of dehydroglyasperin c against
carbon tetrachloride-induced liver damage in mice. Food Sci Biotechnol 23:547–553
Seon MR, Park SY, Kwon SJ, Lim SS, Choi HJ, Park H, Lim DY, Kim JS, Lee CH, Kim J,
Park JH (2012) Hexane/ethanol extract of Glycyrrhiza uralensis and its active compound
isoangustone A induce G1 cycle arrest in DU145 human prostate and 4T1 murine mammary
cancer cells. J Nutr Biochem 23:85–92
Sharifzadeh M, Shamsa F, Shiran S, Karimfar MH, Miri AH, Jalalizadeh H, Gholizadeh S, Salar F,
Tabrizian K (2008) A time course analysis of systemic administration of aqueous licorice
extract on spatial memory retention in rats. Planta Med 74:485–490
Sharma V, Agrawal RC (2013) Glycyrrhiza glabra—A plant for the future. Mintage J Pharm Med
Sci 2(3):15–20
Sharma V, Agrawal RC, Pandey S (2013) Phytochemical screening and determination of
anti-bacterial and anti-oxidant potential of Glycyrrhiza glabra root extracts. J Envir Res Dev 7
(4):1552–1558
Shebl RI, Amin MA, Emad-Eldin A, Bin DS, Mostafa AS, Ibrahim EH, Mohamed AF (2012)
Antiviral activity of liquorice powder extract against varicella zoster virus isolated from
Egyptian patients. Chang Gung Med J 35:231–239
Sheehan MP, Atherton DJ (1992) A controlled trial of traditional Chinese medicinal plants in
widespread non-exudative atopic eczema. Brit J Dermatol 126(2):179–184
Sheela ML, Ramakrishna MK, Salimath BP (2006) Angiogenic and proliferative effects of the
cytokine VEGF in Ehrlich ascites tumor cells is inhibited by Glycyrrhiza glabra. Int
Immunopharmacol 6:494–498
Shen X, Xiao P, Liu C (2007) Research and application of Radix Glycyrrhizae. Asian J
Pharmacodyn Pharmacokinet 7:181–200
Sheth VM, Pandya AG (2011) Melasma: a comprehensive update: part II. J Am Acad Dermatol
65:699–714
Shetty TK, Satav JG, Nair CKK (2002) Protection of DNA and microsomal membranes in vitro by
Glycyrrhiza glabra L. against gamma irradiation. Phytother Res 16:576–578
Shetty AV, Thirugnanam S, Dakshinamoorthy G, Samykutty A, Zheng G, Chen A, Bosland MC,
Kajdacsy-Balla A, Gnanasekar M (2011) 18alpha-glycyrrhetinic acid targets prostate cancer
cells by down-regulating inflammation-related genes. Int J Oncol 39:635–640
Shi W, Norton JM, Miller BE, Pace MG (1999) Effects of aeration and moisture during windrow
composting on the nitrogen fertilizer values of dairy waste composts. Appl Soil Ecol 11(1):17–
28
Shi Y, Wu D, Sun Z, Yang J, Chai H, Tang L, Guo Y (2012) Analgesic and uterine relaxant effects
of isoliquiritigenin, a flavone from Glycyrrhiza glabra. Phytother Res 26:1410–1417
Shibata S (2000) A drug over the millennia: pharmacognosy, chemistry, and pharmacology of
licorice. Yakugaku Zasshi 120:849–862 (in Japanese)
122 8 Economic Importance

Shin EM, Zhou HY, Guo LY, Kim JA, Lee SH, Merfort I, Kang SS, Kim SM, Kim S, Kim YS
(2008) Anti-inflammatory effects of glycyrol isolated from Glycyrrhiza uralensis in
LPS-stimulated RAW264.7 macrophages. Int Immunopharmacol 8:1524–1532
Shinwari ZK, Khan I, Naz S, Hussain A (2009) Assessment of antibacterial activity of three plants
used in Pakistan to cure respiratory diseases. Afr J Biotechn 8(24):7082–7086
Shiota G, Harada K, Ishida M, Tomie Y, Okubo M, Katayama S, Ito H, Kawasaki H (1999)
Inhibition of hepatocellular carcinoma by glycyrrhizin in diethylnitrosamine-treated mice.
Carcinogenesis 20:59–63
Shirinyan E, Panosyan A, Barikyan M, Avakyan O (1988) New antistress or compounds from
licorice. Izv Akad Nauk USSR 6:932–936 (in Russian)
Singh M (2010) Comparative phytochemical and antioxidant study of aqueous extracts of
Glycyrrhiza glabra (mulethi) and Piper longum (long pepper). Int J Drug Res Tech 2:203–207
Siracusa L, Saija A, Cristani M, Cimino F, D’Arrigo M, Trombetta D, Rao F, Ruberto G (2011)
Phytocomplexes from liquorice (Glycyrrhiza glabra L.) leaves—Chemical characterization and
evaluation of their antioxidant, anti-genotoxic and anti-inflammatory activity. Fitoterapia 82
(4):546–556
Škrovánková S, Mišurcová L, Machů L (2012) Chapter three—antioxidant activity and protecting
health effects of common medicinal plants. Adv Food Nut Res 67:75–139
Smirnov VS, Zarubaev VV, Anfimov PM, Shtro AA (2012) Effect of a combination of
glutamyl-tryptophan and glycyrrhizic acid on the course of acute infection caused by influenza
(H3H2) virus inmice. Vopr Virusol 57:23–27
Snowden R, Harrington H, Morrill K, Jeane L, Garrity J, Orian M, Lopez E, Rezaie S,
Hassberger K et al (2014) A comparison of the anti-Staphylococcus aureus activity of extracts
from commonly used medicinal plants. J Altern Complement Med 20:375–382
Sokolov S, Zamotayev I (1985) Directory of medicinal plants. Medicina, Moscow (in Russian)
Song NR, Lee E, Byun S, Kim JE, Mottamal M, Park JH, Lim SS, Bode AM, Lee HJ, Lee KW,
Dong Z (2013) Isoangustone A, a novel licorice compound, inhibits cell proliferation by
targeting PI3K, MKK4, and MKK7 in human melanoma. Cancer Prev Res (Phila) 6:1293–
1303
Song W, Si L, Ji S, Wang H, Fang X-M, Yu L-Y, Li R-Y, Liang L-N, Zhou D, Ye M (2014)
Uralsaponins M-Y, antiviral triterpenoid saponins from the roots of Glycyrrhiza uralensis.
J Nat Prod 77:1632–1643
Soufy H, Yassein S, Ahmed AR, Khodier MH, Kutkat MA, Nasr SM, Okda FA (2012) Antiviral
and immune stimulant activities of glycyrrhizin against duck hepatitis virus. Afr J Tradit
Complement Altern Med 9(3):389–395
Stanikzai MT (2007) Market report liquorice. Multistakeholder programme natural ingredients
Afghanistan. www.tloafghanistan.org/Liquorice%20Market%20Report.pdf
Statti GA, Tundis R, Sacchetti G, Muzzoli M, Bianchi A, Menichini F (2004) Variability in the
content of active constituents and biological activity of Glycyrrhiza glabra. Fitoterapia 75:371–
374
Subramoniam A, Pushpangadan P (1999) Development of phytomedicines for liver diseases.
Indian J Pharmacol 31:166–175
Sui X, Yin J, Ren X (2010) Antiviral effect of diammonium glycyrrhizinate and lithium chloride
on cell infection by pseudorabies herpesvirus. Antiviral Res 85:346–353
Tamir S, Eizenberg M, Somjen D, Stern N, Shelach R, Kaye A, Vaya J (2000) Estrogenic and
antiproliferative properties of glabridin from licorice in human breast cancer cells. Cancer Res
60:5704–5709
Tanaka Y, Kikuzaki H, Fukuda S, Nakatani N (2001) Antibacterial compounds of licorice against
upper airway respiratory tract pathogens. J Nutr Sci Vitaminol 47:270–273
Tandon A, Tandon BN, Bhujwala RA (2002) Clinical spectrum of acute sporadic hepatitis E and
possible benefit of glycyrrhizin therapy. Hepatol Res 23:55–61
References 123

Tanifuji S, Aizu-Yokota E, Funakoshi-Tago M, Sonoda Y, Inoue H, Kasahara T (2010)

Licochalcones suppress degranulation by decreasing the intracellular Ca2+ level and tyrosine
phosphorylation of ERK in RBL-2H3 cells. Int Immunopharmacol 10:769–776
Tharkar PR, Tatiya AU, Shinde PR, Surana SJ, Patil UK (2010) Antifungal activity of Glycyrrhiza
glabra Linn. and Emblica officinalis Gaertn. by direct bioautography method. Int J Pharm Res
2:1547–1549
Thiyagarajan P, Chandrasekaran CV, Deepak HB, Agarwal A (2011) Modulation of
lipopolysaccharide-induced pro-inflammatory mediators by an extract of Glycyrrhiza glabra
and its phytoconstituents. Inflammopharmacology 19:235–241
Timofeyer V (1984) Farm Zh (Kiev) 5:57–60
Treutwein J, Cergel S, Runte J, Nowak A, Konstantinidou-Doltsinis S, Kleeberg H, Schmitt A
(2010) Efficacy of Glycyrrhiza glabra extract fractions against phytopathogenic fungi.
Julius-Kühn-Archiv 428:82
Tripathi M, Singh BK, Kakkar P (2009) Glycyrrhizic acid modulates t-BHP induced apoptosis in
primary rat hepatocytes. Food Chem Toxicol 47:339–347
Tsai JP, Hsiao PC, Yang SF, Hsieh SC, Bau DT, Ling CL, Pai CL, Hsieh YH (2014)
Licochalcone A suppresses migration and invasion of human hepatocellular carcinoma cells
through downregulation of MKK4/JNK via NFkappaB mediated urokinase plasminogen
activator expression. PLoS ONE 9:e86537
Tsuda T, Kubota K, Yasuda K, Nishikava S, Sugaya A, Sugaya E (1986) Effects of Chinese herbal
medicine “Kanbalu-Taiso-To” on transmembrane ionic currents and its local anesthetic action.
J Ethnopharmacol 17(3):257–261
Tyler VE, Bradly LR, Robbers JE (1988) Pharmacognosy, 9th edn. Lea and Febiger, Philadelphia,
PA, pp 68–69
Van Marle J, Aarsen PN, Lind A, van Weeren Kramer J (1981) Deglycyrrhizinised liquorice
(DGL) and the renewal of rat stomach epithelium. Eur J Pharmacol 72:219–225
Van Rossum TG, Vulto AG, Hop WC, Schalm SW (1999) Pharmacokinetics of intravenous
glycyrrhizin after single and multiple doses in patients with chronic hepatitis C infection. Clin
Ther 21:2080–2090
Van Rossum TG, Vulto AG, Hop WC, Schalm SW (2001) Glycyrrhizin-induced reduction of ALT
in European patients with chronic hepatitis C. Am J Gastroenterol 96:2432–2437
Varsha S, Agrawal RC, Sonam P (2013) Phytochemical screening and determination of
anti-bacterial and anti-oxidant potential of Glycyrrhiza glabra root extracts. J Environ Res Dev
7(4):1552–1558
Vaya J, Belinky PA, Aviram M (1997) Antioxidant constituents from licorice roots: isolation,
structure elucidation and antioxidative capacity toward LDL oxidation. Free Radic Biol Med
23:302–313
Ved DK, Goraya GS (2007) Demand and supply of medicinal plants in India. National Medicinal
Plants Board, New Delhi. Foundation for revitalization of local health traditions, Bangalore;
XV
Vibha JB, Choudhary K, Singh M, Rathore MS, Shekhawat NS (2009) A study on
pharmacokinetics and therapeutic efficacy of Glycyrrhiza glabra: a miracle medicinal herb.
Botany Res Int 2(3):157–163
Villinski JR, Bergeron C, Cannistra JC, Gloer JB, Coleman CM, Ferreira D, Azelmat J, Grenier D,
Gafner S (2014) Pyrano-isoflavans from Glycyrrhiza uralensis with antibacterial activity
against Streptococcus mutans and Porphyromonas gingivalis. J Nat Prod 77:521–526
Vivekanand JHA (2010) Herbal medicines and chronic kidney disease. Nephrology 15(2):10–17
Wananukul S, Chatproedprai S, Chunharas A, Limpongsanuruk W, Singalavanija S, Nitiyarom R,
Wisuthsarewong W (2013) Randomized, double-blind, split-side, comparison study of
moisturizer containing licochalcone A and 1% hydrocortisone in the treatment of childhood
atopic dermatitis. J Med Assoc Thai 96:1135–1142
Wang ZY, Nixon DW (2001) Licorice and cancer. Nutr Cancer 39:1–11
124 8 Economic Importance

Wang ZY, Athar M, Bickers DR (2000) Licorice in foods and herbal drugs: chemistry,
pharmacology, toxicology and uses. In: Mazza G, Oomah BD (eds) Herbs, botanicals and teas.
Technomic Publishing Co., Lancaster, PA, pp 321–335
Wang W, Hu X, Zhao Z, Liu P, Hu Y, Zhou J, Zhou D, Wang Z, Guo D, Guo H (2008)
Antidepressant-like effects of liquiritin and isoliquiritin from Glycyrrhiza uralensis in the
forced swimming test and tail suspension test in mice. Progress in Neuro-Psychopharm Biol
Psych 32:1179–1184
Wang CY, Kao TC, Lo WH, Yen GC (2011) Glycyrrhizic acid and 18beta-glycyrrhetinic acid
modulate lipopolysaccharide-induced inflammatory response by suppression of NF-kappaB
through PI3K p110 delta and p110 gamma inhibitions. J Agric Food Chem 59:7726–7733
Wang YG, Zhou JM, Ma ZC, Li H, Liang QD, Tan HL, Xiao CR, Zhang BL, Gao Y (2012)
Pregnane X receptor mediated-transcription regulation of CYP3A by glycyrrhizin: a possible
mechanism for its hepatoprotective property against lithocholic acid-induced injury. Chem Biol
Interact 200:11–20
Wang J, Chen X, Wang W, Zhang Y, Yang Z, Jin Y, Ge HM, Li E, Yang G (2013a) Glycyrrhizic
acid as the antiviral component of Glycyrrhiza uralensis Fisch. against coxsackievirus A16 and
enterovirus 71 of hand foot and mouth disease. J Ethnopharmacol 147:114–121
Wang Z, Cao Y, Paudel S, Yoon G, Cheon SH (2013b) Concise synthesis of licochalcone C and
its regioisomer, licochalcone H. Arch Pharm Res 36:1432–1436
Wang KL, Hsia SM, Chan CJ, Chang FY, Huang CY, Bau DT, Wang PS (2013c) Inhibitory
effects of isoliquiritigenin on the migration and invasion of human breast cancer cells. Expert
Opin Ther Targets 17:337–349
Wang L, Wang Z, Gao W, Chen J, Yang M, Kuang Y, Huang L, Chen S (2013d) Simultaneous
determination of aflatoxin B1 and ochratoxin A in licorice roots and fritillary bulbs by
solidphase extraction coupled with high-performance liquid chromatography-tandem mass
spectrometry. Food Chem 138:1048–1054
Whorwood CB, Sheppard MC, Stewart PM (1993) Licorice inhibits 11 beta-hydroxysteroid
dehydrogenase messenger ribonucleic acid levels and potentiates glucocorticoid hormone
action. Endocrinology 132:2287–2292
Wittschier N, Faller G, Hensel A (2009) Aqueous extracts and polysaccharides from liquorice
roots (Glycyrrhiza glabra L.) inhibit adhesion of Helicobacter pylori to human gastric mucosa.
J Ethnopharmacol 125:218–223
Wolkerstorfer A, Kurz H, Bachhofner N, Szolar OH (2009) Glycyrrhizin inhibits influenza A virus
uptake into the cell. Antiviral Res 83:171–178
Won SR, Kim SK, Kim YM, Lee PH, Ryu JH, Kim JW, Rhee HI (2007) Licochalcone A: A lipase
inhibitor from the roots of Glycyrrhiza uralensis. Food Res Int 40:1046–1050
Wu X, Zhang L, Gurley E, Studer E, Shang J, Wang T, Wang C, Yan M, Jiang Z, Hylemon PB,
Sanyal AJ, Pandak WM Jr, Zhou H (2008) Prevention of free fatty acid-induced hepatic
lipotoxicity by 18beta-glycyrrhetinic acid through lysosomal and mitochondrial pathways.
Hepatology 47:1905–1915
Wu TY, Khor TO, Saw CL, Loh SC, Chen AI, Lim SS, Park JH, Cai L, Kong AN (2011)
Anti-inflammatory/Anti-oxidative stress activities and differential regulation of Nrf2-mediated
genes by non-polar fractions of tea Chrysanthemum zawadskii and licorice Glycyrrhiza
uralensis. AAPS J 13:1–13
Wu F, Jin Z, Jin J (2013) Hypoglycemic effects of glabridin, a polyphenolic flavonoid from
licorice, in an animal model of diabetes mellitus. Mol Med Rep 7:1278–1282
Xiao XY, Hao M, Yang XY, Ba Q, Li M, Ni SJ, Wang LS, Du X (2011) Licochalcone A inhibits
growth of gastric cancer cells by arresting cell cycle progression and inducing apoptosis.
Cancer Lett 302:69–75
Xiao ZW, Zhang W, Ma L, Qiu ZW (2014) Therapeutic effect of magnesium isoglycyrrhizinate in
rats on lung injury induced by paraquat poisoning. Eur Rev Med Pharmacol Sci 18:311–320
Xie XW (2017) Liquiritigenin attenuates cardiac injury induced by high fructose-feeding through
fibrosis and inflammation suppression. Biomed Pharmacother 86:694–704
References 125

Yang L, Wang L, Pan J, Xiang L, Yang M, Logrieco AF (2010) Determination of ochratoxin A in

traditional Chinese medicinal plants by HPLC-FLD. Food Addit Contam A 27:989–997
Yang N, Patil S, Zhuge J, Wen MC, Bolleddula J, Doddaga S, Goldfarb J, Sampson HA, Li XM
(2013) Glycyrrhiza uralensis flavonoids present in anti-asthma formula, ASHMITM, inhibit
memory Th2 responses in vitro and in vivo. Phytother Res 27(9):1381–1391
Yang R, Wang LQ, Yuan BC, Liu Y (2015) The pharmacological activities of licorice. Planta Med
81(18):1654–1669
Yao K, Chen H, Lee MH, Li H, Ma W, Peng C, Song NR, Lee KW, Bode AM, Dong Z, Dong Z
(2014) Licochalcone A, a natural inhibitor of c-Jun N-terminal kinase 1. Cancer Prev Res
(Phila) 7:139–149
Yehuda I, Madar Z, Szuchman-Sapir A, Tamir S (2011) Glabridin, a phytoestrogen from licorice
root, up-regulates manganese superoxide dismutase, catalase and paraoxonase 2 under glucose
stress. Phytother Res 25:659–667
Yin G, Cao L, Xu P, Jeney G, Nakao M, Lu C (2011) Hepatoprotective and antioxidant effects of
Glycyrrhiza glabra extract against carbon tetrachloride (CCl(4))-induced hepatocyte damage in
common carp (Cyprinus carpio). Fish Physiol Biochem 37:209–216
Yoğunlu A (2011) Tunceli ekonomik değeri olan bitkiler raporu-“Sektörel araştırmalar serisi-5”.
Fırat Development Agency. www.fka.org.tr
Yokota T, Nishio H, Kubota Y, Mizoguchi M (1998) The inhibitory effect of glabridin from
licorice extracts on melanogenesis and inflammation. Pigment Cell Res 11:355–361
Yoon G, Jung YD, Cheon SH (2005) Cytotoxic allylretrochalcone from the roots of Glycyrrhiza
inflata. Chem Pharm Bull 53:694–695
Yoshida T, Yoshida S, Kobayashi M, Herndon DN, Suzuki F (2010) Pivotal advance: glycyrrhizin
restores the impaired production of b-defensins in tissues surrounding the burn area and
improves the resistance of burn mice to Pseudomonas aeruginosa wound infection. J Leukoc
Biol 87:35–41
Yu XY, Lin SG, Zhou ZW, Chen X, Liang J, Yu XQ, Chowbay B, Wen JY, Duan W, Chan E,
Li XT, Cao J, Li CG, Xue CC, Zhou SF (2007) Role of P-glycoprotein in limiting the brain
penetration of glabridin, an active isoflavan from the root of Glycyrrhiza glabra. Pharm Res
24:1668–1690
Yuan X, Li T, Xiao E, Zhao H, Li Y, Fu S, Gan L, Wang Z, Zheng Q, Wang Z (2014)
Licochalcone B inhibits growth of bladder cancer cells by arresting cell cycle progression and
inducing apoptosis. Food Chem Toxicol 65:242–251
Yumatni Y, Shigeree T, Kazo T, Isav O, Trukasa T (1980) J Fac Appl Biol Sci Hiroshima Univ 19
(1):113–120
Zamansoltani F, Nassiri-Asl M, Sarookhani MR, Jahani-Hashemi H, Zangivand AA (2009)
Antiandrogenic activities of Glycyrrhiza glabra in male rats. Int J Androl 32:417–422
Zani F, Cuzzoni MT, Daglia M, Benvenuti S, Vampa G, Mazza P (1993) Inhibition of
mutagenicity in Salmonella typhimurium by Glycyrrhiza glabra extract, glycyrrhizinic acid,
18alpha- and 18beta-glycyrrhetinic acids. Planta Med 59:502–507
Zhai D, Zhao Y, Chen X, Guo J, He H, Yu Q, Yang J, Davey AK, Wang J (2007) Protective effect
of glycyrrhizin, glycyrrhetic acid and matrine on acute cholestasis induced by alpha-naphthyl
isothiocyanate in rats. Planta Med 73:128–133
Zhang Y, Zhang L, Zhang Y, Xu JJ, Sun LL, Li SZ (2016) The protective role of liquiritin in high
fructose-induced myocardial fibrosis via inhibiting NF-jB and MAPK signaling pathway.
Biomed Pharmacother 84:1337–1349
Zhao ZY, Wang WX, Guo HZ, Guan ZQ, Zhou DF (2006) Anti-depressive effect of liquiritin on
chronic stress depression in rats. Chin J Clin Rehabil 27:69–72
Zhao Z, Wang W, Guo H, Zhou D (2008) Antidepressant-like effect of liquiritin from Glycyrrhiza
uralensis in chronic variable stress induced depression model rats. Behav Brain Res 194:108–
113
Zhou X, Zhao L, Liu X, Li X, Jia F, Zhang Y, Wang Y (2012a) Antimycobacterial and synergistic
effects of 18beta-glycyrrhetinic acid or glycyrrhetinic acid-30-piperazine in combination with
isoniazid, rifampicin or streptomycin against Mycobacterium bovis. Phytother Res 26:253–258
126 8 Economic Importance

Zhou T, Deng X, Qiu J (2012b) Antimicrobial activity of licochalcone E against Staphylococcus

aureus and its impact on the production of staphylococcalalpha-toxin. J Microbiol Biotechnol
22:800–805
Zhu YP (1998) Chinese materia medica: chemistry, pharmacology and applications. Harwood
Academic Publishers, Amsterdam
Zhu Z, Li C, Wang X, Yang Z, Chen J, Hu L, Jiang H, Shen X (2010) 2,2,4-trihydroxychalcone
from Glycyrrhiza glabra as a new specific BACE1 inhibitor efficiently ameliorates memory
impairment inmice. J Neurochem 114:374–385
Chapter 9
Cultivation

Theophrastus has referred to the liquorice plant, mentioning that Romans cultivated
it after thirteenth century and called it as Radix dulis. Early popular books on herbal
medicine provide most through accounts related to the uses of Glycyrrhiza glabra
from Europe. It was cultivated in England for the first time in 1562 (Roshan et al.
2012; Trease and Evans 1983). Currently, the plant is cultivated in different regions
of India, Iran, Turkey, Greece, Spain, and Russia. The trade is still observed in
Spain, Iraq, Italy, Egypt, Belgium, France, and Germany (Anilkumar et al. 2012;
Kokate et al. 2009). In India, it has been reported to show a prolific growth in
Patiala, Hissar of Haryana State (Singh 1964), Uttar Pradesh (Uniyal et al. 1978),
and in South India (Ahmad and Khaleefathullah 1986).
Chinese liquorice is considered to be of very good quality (Shah 1995). It can be
cultivated or obtained from wild plants as well, but cultivation is very successful in
vertically and horizontally grown plants on deep fertile sandy soils near streams in
the subtropics. Dry seasons are beneficial to the crop and it thrives well in warm
regions, where the annual rainfall is not over 50 cm. Fertile sandy or sandy loam
soils without stones are optimal for liquorice. Manuring is not required unless if the
soil is fertile (Singh et al. 1984). The common method of propagation is by
replanting young pieces of stolon, but seed can also be sown. The underground
organs are sufficiently developed by the end of the third or fourth year at which
stage they are dug up and washed (Anilkumar et al. 2012). Yields of 10–12 ton/ha
have been considered good for some time, this only being attained in the fourth year
of growth (Rogers 2014). The bruised root has a characteristic sweet pungent smell.
Plants are slow to settle in and do not produce much growth in their first 2 years
after being moved. The young growth is also very susceptible to damage by slugs
and so the plant will require some protection in its first few years (Rogers 2014).
Different harvesting procedures have been outlined in detail by Singh et al. (1984).
Regeneration occurs from the underground root system after harvesting and the
plant is ready for further harvesting after 2–5 years (Rao 1993).
Propagation is generally performed by employing 15 cm long stolons with two or
three buds obtained from the planting stock. Old crowns are also used as planting
materials (Singh et al. 1984). Germination capacity of G. glabra seeds at different
stages has been studied at length by Gladyshev and Kerbabaev (1967). Seeds in the
waxy-ripe stage have been found to show highest germination rate. Slow germination
of scarified seeds of liquorice has been recorded by Yarkonis (1976). The cuttings
planted and irrigated in the ridges 45–60 cm height facilitate the root development.

© The Author(s) 2017 127

M. Öztürk et al., Liquorice, SpringerBriefs in Plant Science,
https://doi.org/10.1007/978-3-319-74240-3_9
128 9 Cultivation

Poor quality of liquorice yield results if plants are allowed to set seeds. Removal of
flowers immediately after their emergence yields a good quality of liquorice (Singh
et al. 1984). Liquorice root production is successfully enhanced by treating cuttings
with 0.0025% succinic acid followed by an application of nitrogen and phosphorus,
root weight reaches twofold in 3-year-old plants (Badalov 1978). Mohammad and
Rehman (1985) have compared its cultivation in irrigated and rainfed sand dunes.
Survival percentage has been observed to be more in irrigated sandy habitats. To
achieve stable yields of liquorice, irrigation of G. glabra is reported to be a must in
oasis region sands (Durmeshev 1986). According to Osipov (1987), variations in the
yield of root mass of liquorice results from different hydrogeologic regimes all along
the Amudarya floodplain. Increased growth has been found in the areas, where subsoil
waters are at a depth of 177–195 cm.
Normally, rhizome cuttings are used to grow the plant. In addition, the harvested
crowns taken from mature crops can also be used by laying these out in shallow
furrows (Molyneux 1975; Singh et al. 1984). Plant spacings to establish the crop
vary between 0.33 m  0.67 m (45,000 plants/ha) in England (Molyneux 1975),
0.45–0.6 m  0.9 m (18,500–24,400 plants/ha) in India (Singh et al. 1984), 0.4–
0.5 m  0.6–0.7 m (28,600–41,700 plants/ha) in Italy (Marzi et al. 1993b), and
0.3 m  0.9–1.2 m (27,800–37,000 plants/ha) in Australia (Whitten 1997). Marzi
et al. (1993b) have grown liquorice in rows spaced from 0.4 to 1.2 m and within
row plant spacings of 0.4 to 1.2 m to give a plant population range from 6900 to
62,500 plants/ha. Fresh root yields have been maximized (20.4 t/ha) at a plant
population of 42,000 plants/ha with the low and high plant population extremes
producing root yields of 7–9 t/ha. Similarly, Leto et al. (1996) have compared the
liquorice grown in 0.7 m spaced rows with intra-row spacings of 0.3–0.9 m to give
a plant population range from 15,900 to 47,600 plants/ha in Sicily. The fresh root
yield at one site has increased from 6.4 to 12.2 t/ha as the plant populations
increased to 47,600 plants/ha, but on the second site a plant population of
20,400 plants/ha has given a root yield (12.4 t/ha) similar to that from the highest
plant population (Leto et al. 1996; Douglas et al. 2004).
This plant is slow to establish from the unrooted cuttings. However, in Italy and
Pakistan, irrigation has been reported to improve the establishment by 7% to over 90%
(Mohammad and Rehman 1985; Marzi et al. 1993b). During the first 2 years of slow
growth after planting, inter-row cropping may be undertaken to provide income
(Molyneux 1975; Whitten 1997). However, Singh et al. (1984) and Douglas et al.
(2004) do not recommend this practice. The inter-row cropping with cereals and rye-
grass are reported to depress the root yield in liquorice (De Mastro et al. 1993; Marzi
et al. 1993b; Bezzi and Aiello 1996). Liquorice develops 2–3.5 m-deep root system,
but top 300 mm of the soil system embody most of the root mass (Duke 1981; Leto
et al. 1996; Martin et al. 1996). Roots are generally harvested from the top 1 m.
However, complete root harvests are also done with fresh root yields of 50 t/ha
(Molyneux 1975; Duke 1981; Anonymous 1982). Usually, 3–5 years after establish-
ment harvests are done (Molyneux 1975; Duke 1981; Singh et al. 1984). In Italy, fresh
root yields of 14–26 t/ha have been harvested from 3- or 4-year-old experimental plots
9 Cultivation 129

(Marzi et al. 1993b; Bezzi and Aiello 1996; Leto et al. 1996). An increase in the root
production from 14 to 23 t/ha has been reported by delaying harvest from 3 to 5 years
(Bezzi and Aiello 1996). Irrigation also increased the fresh root yields in Italy by 30%
to 26.5 t/ha on a sandy clay soil following irrigation (Marzi et al. 1993b). In Pakistan,
dry root yields have gone up by 13% to 6.1 t/ha on sand dunes (Mohammad and
Rehman 1985). As against this, the experimental studies carried out in Italy show that a
rainfed liquorice crop grown for 4 years on a deep silty clay soil gives a fresh root yield
of 24.3 t/ha with irrigation depressing the root yield by 17% (De Mastro et al. 1993).
Liquorcie is said to prefer fertile soils, which are necessary for its good growth (Singh
et al. 1984; Whitten 1997). Singh et al. (1984) are recommending an application of 37–
49 t/ha of farmyard manure before planting, however on fertile soils, fertilizer is
unnecessary. Some fertilizer comparisons have been published (Douglas et al. 2004).
According to Marzi et al. (1993b), a single application of a fertilizer mixture containing
100 kg/ha nitrogen (N), 44 kg/ha phosphorus (P), and 166 kg/ha potassium
(K) increases the fresh root yield of a 3-year-old crop by 34% to 26.5 t/ha. No benefit
has been recorded by applying each element separately. Maheshwari et al. (1984) have
studied this aspect in India, but they have failed to get a response to 120 kg/ha N and
120 kg/ha P applied in addition to a basal dressing of 40 t/ha of farmyard manure. No
effect on different rates of N and P fertilizers on glycyrrhizin concentration has been
observed by Maheshwari et al. (1984).
According to the data published by the American Botanical Council (1998) and
WHO (1999), as a medicinal herb liquorice root must contain at least 4% (40 g/kg)
glycyrrhizin (or glycyrrhizic acid, or glycyrrhizinic acid). The root under normal
conditions contains 2–9% glycyrrhizin (WHO 1999) with an average of 7–10% in
the Mediterranean region (Nieman 1957), but with concentrations as high as 15%
are reported, depending on variety, age, where the plant is grown, and its harvesting
time (Fenwick et al. 1990; Hayashi et al. 1998). An increase in the glycyrrhizin
concentration in roots and rhizomes is found as they get older and become larger in
diameter (Hayashi et al. 1993; Marzi et al. 1993a; Usai et al. 1995). Higher gly-
cyrrhizin concentrations are found in tap roots as compared to the rhizomes of
pot-grown plants with the relative differences reduced in plants harvested after
3 years instead of 2 (De Mastro and Circella 1993; Marzi et al. 1993a). The rhi-
zomes have shown higher glycyrrhizin concentration in the field studies than tap
roots harvested after 5 years of growth (Bezzi and Aiello 1996).
In New Zealand, this plant is not a commercial crop. Very little information is
available on its productive potential as well as agronomic requirements to achieve
high-quality root production (Douglas et al. 2004). Although the preliminary
research was done in the early 1980s (Palmer 1987). More potential has been shown
during a commercial trial crop established in 1987, which gave fresh root yields up
to 22 t/ha after 7 years of growth (Martin et al. 1996; Douglas et al. 2004). The
licorice (G. glabra) root production studied by Douglas et al. (2004) in Central
Otago, Canterbury, and Waikato regions of New Zealand over 4 years has revealed
that an increase in the plant populations at establishment has a large effect on
production. Maximum root and rhizome productions are achieved with plant
130 9 Cultivation

populations above 24,000 plants/ha. Low plant densities favor rhizome production
and higher densities favor root production. Sampling roots and rhizomes to 900 mm
have shown that majority of production is found in the top 300 mm. Roots har-
vested from the ground below 300 mm contain less glycyrrhizin than the roots dug
from the surface (Douglas et al. 2004). Glycyrrhizin concentration increases on
yearly basis and has surpassed the minimum international standard of 4% in the first
harvest at Waikato but not until the third harvest in South Island. During the third
harvest, liquorice from Waikato as well as Canterbury contained similar amounts of
glycyrrhizin but with 90% of it was in roots dug from 0 to 300 mm soil layer in the
Waikato and in the 0 to 600 mm soil layer in Canterbury. The trials by Douglas
et al. (2004) depict this plant can be grown in New Zealand with fresh root and
rhizome yields of 17–28 t/ha in the second and third years of production and with a
glycyrrhizin content above the minimum international standard. The studies on
liquorice or mulahatti (G. glabra) undertaken by Dagar et al. (2015) have revealed
that it can be successfully grown on alkali soils. Besides getting (2.4–6.1 tons/ha
forage/year), a root biomass of 6.0–7.9 tons/ha is obtained in 3 years with a great
economic input for the grower. The sodic lands are reclaimed substantially in this
way by reducing soil pH and exchangeable sodium percentage after growing this
crop on such soils.
Both, genetic background and environmental conditions play key roles in
liquorice cultivation. Several workers have investigated the specific effects on the
growth of this plant (Miao et al. 2017). The samples of 8-year-old plants collected
from 18 producing regions for investigating the effect of gene and environment on
their characteristics by Miao et al. (2017) report that, 1-year-old liquorice plants
cultivated in 18 producing regions show significant geographic variations in growth
characteristics as well as glycyrrhizin content, all associated with their ecological
niche (Wei et al. 2012a, b). Kojoma et al. (2011) have analyzed the glycyrrhizin
content of 5-year-old liquorice plants and reports various genetic strains for gly-
cyrrhizin and liquiritin synthesis within a population of plants. Later Yu et al.
(2013) have reported that genotype and the environment are highly effective in the
bioactive components of 2-year-old cultivated licorice from four producing regions.
In view of this, exploring the relationship between more sources as well as longer
growth period and quality of cultivated plants is important in this connection. Miao
et al. (2017) report that growth characteristics as well as glycyrrhizin and liquiritin
contents of 8-year-old liquorice vary in different provenances. According to them,
the contents of glycyrrhizin and liquiritin of different sources have shown signifi-
cant variation owing to genetic expression. The growth characteristics are also
negatively correlated with temperature and moisture, while the glycyrrhizin and
liquiritin contents are positively correlated with temperature and negatively corre-
lated with moisture, indicating there are significant geographic variations in the
growth of 8-year-old plants, associated with their genetic expression together with
the ecological environment (Miao et al. 2017).
Reclamation of desert sands with liquorice cultivation has been demonstrated in
sandy habitats adjacent to oases in the Russian deserts (Kel’dzhaev and Gladyshev
1982). According to Varganov and Gladyshev (1981) cultivation of liquorice on
9 Cultivation 131

oasis sands for the stabilization of sandy habitats and quick improvement of soil is
very important. A similar report has been published by Mohammad and Rehman
(1985). These findings clearly depict that liquorice plays an important role in the
stabilization of sand dunes.

References

Ahmad V, Khaleefathullah S (1986) In: Abstract of the 34th annual congress on medicinal plants
research, Hamburg, Planta Medica
American Botanical Council (1998) The complete German Commission E monographs. German
(trans from German: Klein S and edited by Blumenthal M and others). Austin, Texas,
American Botanical Council
Anilkumar D, Joshi H, Nishteswar K (2012) Review of Glycyrrhiza glabra (Yastımadhu)—a
broad spectrum herbal drug. Pharm Sci Monit 3171–3195. ISSN: 0976-7908
Anonymous (1982) Glycyrrhiza glabra L., liquorice, family Leguminosae. In: Markets for
selected medicinal plants and their derivatives. Geneva, International Trade Centre, UNCTAD/
GATT, pp 133–143
Badalov M (1978) Ref Zh 9(55):783
Bezzi A, Aiello N (1996) Liquorice (Glycyrrhiza glabra L.) cultivation in different pedoclimatic
environments of central and northern Italy. Atti convegno internazionale: Coltivazione e
miglioramento di piante officinali, Trento, Italy 2–3 giugno 1994, pp 399–410 (In Italian)
Dagar JC, Yadav RK, Dar SR, Ahamad S (2015) Liquorice (Glycyrrhiza glabra): a potential
salt-tolerant, highly remunerative medicinal crop for remediation of alkali soils. Curr Sci 108
(9):1683–1688
De Mastro G, Circella G (1993) Effect of soil depth and cropping length on the root system growth
in liquorice (Glycyrrhiza glabra L.). Acta Hort 344:518–522
De Mastro G, Marzi V, Ventrelli A (1993) Influence of temporary intercropping on the
productivity of liquorice (Glycyrrhiza glabra L.). Acta Hort 344:523–528
Douglas JA, Douglas MH, Lauren DR, Martin RJ, Deo B, Follett JM, Jensen DJ (2004) Effect of
plant density and depth of harvest on the production and quality of licorice (Glycyrrhiza
glabra) root harvested over 3 years. N Z J Crop Hortic Sci 32(4):363–373
Duke JA (1981) Glycyrrhiza glabra L. Handbook of legumes of world economic importance.
Plenum Press, New York, pp 90–92
Durmeshev S (1986) Izv Akad Nauk Turkm SSR Ser Biol Nauk 0(6):28–33
Fenwick GR, Lutomski J, Nieman C (1990) Liquorice, Glycyrrhiza glabra L.—composition, uses
and analysis. Food Chem 38:119–143
Gladyshev AI, Kerbabaev BB (1967) Izv Akad Nauk Turkm SSR Ser Biol Nauk 2:45–48
Hayashi H, Fukui H, Tabata M (1993) Distribution pattern of saponins in different organs of
Glycyrrhiza glabra. Planta Med 59:351–353
Hayashi H, Hiraoka N, Ikeshiro Y, Yamamoto H, Yoshikawa T (1998) Seasonal variation of
glycyrrhizin and isoliquiritigenin glycosides in the root of Glycyrrhiza glabra L. Biol Pharm
Bull 21(9):987–989
Kel’dhnaev PS, Gladyshev AI (1982) Izv Akad Nauk Turkm SSR Ser Biol Nauk 0(3):19–24
Kojoma M, Hayashi S, Shibata T (2011) Variation of glycyrrhizin and liquiritin contents within a
population of 5-year-old licorice (Glycyrrhiza uralensis) plants cultivated under the same
conditions. Biol Pharm Bull 34:1334
Kokate CK, Purohit AP, Gokhale SB (2009) Pharmacognosy, 43rd edn
Leto C, Carrubba A, Trapani P (1996) Effects of plant population in liquorice (Glycyrrhiza glabra
L.) in a semi-arid Sicilian environment. Atti convegno internazionale: Coltivazione e
miglioramento di piante officinali, Trento, Italy, 2–3 giugno 1994, pp 541–550 (In Italian)
132 9 Cultivation

Maheshwari SK, Yadav S, Gangrade SK (1984) Fertiliser needs of liquorice grown on black cotton
soil. Indian J Agric Sci 54:338–339
Martin RJ, Douglas MH, Heaney AJ (1996) Yield and root distribution in a commercial licorice
crop. In: New crops, new products. New opportunities for Australian agriculture. Vol. 2.
Pulses, oilseeds and horticultural, industrial and bioactive crops. RIRDC research paper no 97/
21, pp 149–153
Marzi V, Circella G, Vampa GM (1993a) Effect of soil depth on the rooting system growth in
Glycyrrhiza glabra L. Acta Hort 331:377–379
Marzi V, Ventrelli G, De Mastro G (1993b) Influence of intercropping and irrigation on
productivity of licorice (Glycyrrhiza glabra L.). Acta Hort 331:71–78
Miao X, Liua R, Liu H, Yu F, Wang J, Wang W, Wei S (2017) Genetic and environmental effect
on the growth characteristics and bioactive components of eight-year-old Glycyrrhiza uralensis
Fisch. Agri Gene 3:57–62
Mohammad N, Rehman S (1985) Performance of Glycyrrhiza glabra in Mastung valley,
Baluchistan. Pak J Agric Res 6(3):176–179
Molyneux F (1975) Licorice production and processing. Food Technol Aust 231–234
Nieman C (1957) Licorice. Adv Food Res 7:339–381
Osipov AP (1987) Izv Akad Nauk Turkm SSR Ser Biol Nauk 6:36–43
Palmer J (1987) Licorice—lessons from Lincoln trials. Dittany 8:46–49
Rao KVS (1993) A review on Licorice. Ancient Sci Life XIII(1–2):57–88
Rogers M (ed) (2014) Licorice. In: Herbalpedia. http://www.herbalpedia.com
Roshan A, Verma NK, Kumar CS, Chandra V, Singh DP, Panday MK (2012) Phytochemical
constituent, pharmacological activities and medicinal uses through the millenia of Glycyrrhiza
glabra Linn: a review. Int Res J Pharm 3(8):45–55
Shah BG (1995) Nighantu Adarsha- Purvatdha, vol I, 1st edn. Jamnagar Gujarat Ayurved
University, pp 502–509
Singh J (1964) Indian Forester 90(80):509–510
Singh AK, Sharma A, Kumar P, Virmani OP (1984) Cultivation and utilization of liquorice
(Glycyrrhiza glabra L.): a review. Curr Res Med Aromat Plants 6(2):98–105
Trease GE, Evans WC (1983) Text book of pharmacognosy. Bailliere and Tindal Publication,
Baltimore
Uniyal MR, Tiwary J, Dixit RS, Purohit GN (1978) J Res Indian Med Yoga Homeopathy 13
(2):112–113
Usai M, Picci V, Atzei AD (1995) Glycyrrhizin variability in subterranean organs of Sardinian
Glycyrrhiza glabra subspecies glabra var. glabra. J Nat Prod 58:1727–1729
Varganov LA, Gladyshev AI (1981) Probl Osvo Pustyn 4:30–40
Wei SL, Wang WQ, Liu CL (2012a) The broad-sense heritability of yield and glycyrrhizin content
of annual licorice (Glycyrrhiza uralensis). Chin J Chin Mater Med 37:553–557
Wei SL, Wang WQ, Wang JY (2012b) Geographic variation and ecological mechanism of growth
characteristics and glycyrrhizin content of annual Gancao (Radix Glycyrrhizae). J Beijing Univ
Chin Med 35:406–411
Whitten G (1997) Licorice, Glycyrrhiza glabra L. Fabaceae. In: Herbal harvest. Commercial
organic production of quality dried herbs. Hawthorn, Bloomings Books, pp 265–269
WHO (1999) WHO monographs on selected medicinal plants, vol 1. World Health Organisation,
Geneva
Yarkonis YA (1976) Liet TSR Moksivr Akad. Darb. Ser C Biol. Mokslai 2:45–52
Yu FL, Wang WQ, Hou JL (2013) The effect of bioactive constituents contents from germplasm
and environment of 2-year-old licorice (Glycyrrhiza uralensis). Chin J Chin Mater Med
38:1479–1482
Chapter 10
Global Perspectives and Future
Approaches

Liquorice is a plant with a rich ethnobotanical history, and used throughout the
world as a drug in traditional folk medicine. The vast range of biological effects
such as anti-inflammatory, antiallergic, antioxidant, antiviral of the phytochemicals
present in extract has been of immense importance in phytotherapeutics. There is an
immense need to modify the natural Glycyrrhiza constituents like glycyrrhizin to
reduce these side effects, thereby generating the advanced versions of the bioactive
compounds to be used as drugs in future medical applications (Sharma and Agrawal
2013). The screening for a particular activity can be achieved using automated
high-throughput assay system to arrive at a “lead” molecule suitable for the
development into a new drug (Eldridge et al. 2002). Glycyrrhizin, glycyrrhetinic
acid, glabridin, and isoliquiritigenin hold a strong promise in designing future
drugs. Derivatives of these compounds are being generated to evaluate their
pharmacological purposes for future drug use. The advances in drug discovery with
tools like the high-throughput system, proteomics, genomics, and informatics (Bio/
chem. and pharmaco) have further enhanced the evaluation of these newly gener-
ated compounds for their future medical applications (Sharma and Agrawal 2013).
Many studies demonstrate that liquorice has beneficial effects for treatment of
severe diseases such as cancer, atherosclerosis, immunodeficiency, hormone defi-
ciency, and viral, skin, and respiratory diseases. However, further studies are
necessary to confirm these effects on the face (Asl and Hosseinzadeh 2012).
The economic and industrial potential of liquorice is unequivocally evident from
its highly diverse intrinsic pharmacological features apart from its use in food
industry. With further advancement in knowledge on its pharmacological activities
and use in food industry, the commercial requirement of this herb will certainly
increase in future. The statistical data on liquorice imports shows the increasing
demand (Stanikzai 2007). To conserve foreign exchange and to meet the increasing
demand, it is highly necessary to focus our attention on liquorice research. Attempts
on various aspects can be made to indigenize its commercial production in a broad
manner by using plant breeding techniques, micropropagation, and in vitro
metabolite production. Many investigations manifest that a large number of food
products/medicinally important compounds of plant origin have been obtained
through plant tissue culture, direct enzyme application, and utilization of whole
cells in biocatalysts in fermentation technology (Rao 1993).
The commercial production of glycyrrhizin by plant cell culture is difficult at present
(Hayashi et al. 1988; Henry et al. 1991). However, glycyrrhizin is obtained from the

© The Author(s) 2017 133

M. Öztürk et al., Liquorice, SpringerBriefs in Plant Science,
https://doi.org/10.1007/978-3-319-74240-3_10
134 10 Global Perspectives and Future Approaches

wild or cultivated Glycyrrhiza plants (Hayashi and Sudo 2009). An overutilization of

wild populations of liquorice has resulted in a reduction in the natural reserves and
desertification of the habitats of these plants, especially in China. In the year 2000,
Chinese government enforced restrictions on the collection of this herb from the wild.
This has resulted in its shortage in the market (Yamamoto et al. 2003). A cultivation of
this plant has been undertaken to compensate for the reduction in the natural reserves;
however, the glycyrrhizin content obtained from these is generally lower. Researchers
have been able to produce 4-year-old adventitious roots with glycyrrhizin levels that
conformed to the Japanese Pharmacopeia standard (not less than 2.5%) (Yamamoto
et al. 2003; Yamamoto and Tani 2005). More research is needed to find methods for
increasing the glycyrrhizin content in the roots of cultivated Glycyrrhiza plants and
obtain a Glycyrrhiza strain that produces high amounts of glycyrrhizin (Yamamoto and
Tani 2005). The cDNA sequences of the enzymes involved in glycyrrhizin biosynthesis
have been reported. There is a possibility of using metabolic engineering to generate
glycyrrhizin-producing plants or microorganisms, which seems to be promising and
must be considered in all upcoming studies (Hayashi et al. 2001; Seki et al. 2008;
Hayashi and Sudo 2009).

References

Asl MN, Hosseinzadeh H (2012) Licorice (Glycyrrhiza species). In: Ram Singh (ed) Genetic
resources, chromosome engineering and crop improvement: medicinal plants, vol 6, Chapter 7.
CRC Press, LLC, Taylor & Francis, USA, pp 935–958
Eldridge GR, Vervoort HG, Lee CM, Cremin PA, Williams CT, Hart SM, George MG,
Johnson M, Zeng L (2002) High throughput method for production and analysis of large
natural product library for drug discovery. Anal Chem 74:3963–3971
Hayashi H, Sudo H (2009) Economic importance of licorice. Plant Biotechnol 26:101–104
Hayashi H, Fukui H, Tabata M (1988) Examination of triterpenoids produced by callus and cell
suspension cultures of Glycyrrhiza glabra. Plant Cell Rep 7:508–511
Hayashi H, Huang P, Kirakosyan A, Inoue K, Hiraoka N, Ikeshiro Y, Kushiro T, Shibuya M,
Ebizuka Y (2001) Cloning and characterization of a cDNA encoding b-amyrin synthase involved in
glycyrrhizin and soyasaponin biosynthesis of Glycyrrhiza glabra. Biol Pharm Bull 24:912–916
Henry M, Edy AM, Desmarest P, Du Manoir J (1991) Glycyrrhiza glabra L. (licorice): Cell
culture, regeneration, and the production of glycyrrhizin. In: Bajaj YPS (ed) Biotechnology in
agriculture and forestry, vol 15. Springer-Verlag, Berlin Heidelberg, pp 270–282
Rao KVS (1993) A review on Licorice. Ancient Sci Life XIII(1–2):57–88
Seki H, Ohyama K, Sawai S, Mizutani M, Ohnishi T, Sudo H, Akashi T, Aoki T, Saito K, Muranaka T
(2008) Licorice b-amyrin 11-oxidase, a cytochrome P450 with a key role in the biosynthesis of the
triterpene sweetener glycyrrhizin. Proc Natl Acad Sci USA 105:14204–14209
Sharma V, Agrawal RC (2013) Glycyrrhiza glabra-A plant for the future. Mintage J Pharm Med
Sci 2(3):15–20
Stanikzai MT (2007) Market report Liquorice. Multistakeholder programme natural ingredients
Afghanistan. www.tloafghanistan.org/Liquorice%20Market%20Report.pdf
Yamamoto Y, Tani T (2005) Field study and pharmaceutical evaluation of Glycyrrhiza uralensis
roots cultivated in China. J Trad Med 22(Supp 1):86–97
Yamamoto Y, Majima T, Saiki I, Tani T (2003) Pharmaceutical evaluation of Glycyrrhiza
uralensis roots cultivated in eastern Nei-Meng-Gu of China. Biol Pharm Bull 26:1144–1149
Chapter 11
Concluding Remarks and Future
Directions of Research

An evaluation of the characteristics for ecological sustainability makes medicinal,

aromatic, and other economically important plants more important. It is not possible
to place a price on these services, but need to be protected as economic indicators
(Costanza and Farber 2002; Farber et al. 2006). The work on the conservation of the
economically important medicinal and other plants in this context has big priority. It
is also necessary in the conservation efforts to look for the scope of cooperation for
these plants with the local people. A protection of genetic resources in this direction
is the most urgent question (Svetlana et al. 2012; Ozturk et al. 2017a). Sustainable
conservation of genetic resources from our natural wealth and for future research is
also very important (Ozturk et al. 2014, 2016).
In the forthcoming 5 decades, the global population is expected to cross the level
of 9 billion, leading to a decrease in the renewable natural resources. The housing
and farmland use will go up moving toward to a decrease in the number of species.
The area of fertile soils will decrease and deforestation will add to the species loss.
The climate change will prove harmful with the depletion of water resources.
Undoubtedly all these impacts will pose great threats to future generations (Svetlana
et al. 2012; Ozturk et al. 2017a). Out of our natural resources, in particular,
availability of medicinal and aromatic plants together with other consumable her-
bals will suffer a great loss (Ozturk et al. 2011, 2012a, b, c, 2017a, b).
An attempt has been made here to enlighten the facts about liquorice; an alternative
natural food and drug resource due to the preventative and medicinal features. Its
extracts can provide a natural solution for seeking an alternative to synthetic drugs. It is
important and necessary to carry out further detailed studies to confirm conservation
biology, physiology, ecology, and biotechnology of this genus.
The estimations say that more than 400 compounds have been isolated from
liquorice taxa, where triterpene saponins and flavonoids are the main constitutes with
broad biological activity. The triterpenoid saponins appear to be the major characteristic
constituents responsible for its sweet taste. The main phenols include liquiritin,
isoliquiritin, and coumarins include liqcoumarin, glabrocoumarone A and B.
The plant extracts and individual biological active compounds exhibit a broad
range of biological activities like antimicrobial, antiviral, anti-ulcer, antitumor,
antioxidant, antiallergic, neuroprotective, anti-inflammatory, hepatoprotective, and
dermatological as confirmed by the pharmacological studies. This herb can be used
in the management of impaired learning, dementia, Alzheimer’s disease. Until now,
no potentially toxic compounds are reported from the investigated taxa. However,

© The Author(s) 2017 135

M. Öztürk et al., Liquorice, SpringerBriefs in Plant Science,
https://doi.org/10.1007/978-3-319-74240-3_11
136 11 Concluding Remarks and Future Directions of Research

some toxic effects are known, such as the use of large doses over a long period
which leads to some severe disorders. The plant can be used as a therapeutic drug in
low doses for major body ailments and presents no concern for safe use.
The healthful characteristics of liquorice and its bioactive constituents such as
glycyrrhizic acid, 18b-glycyrrhetinic acid, carbenoxolone, dehydroglyasperin C, and
dehydroglyasperin D as well as some unique compounds such as glabridin, licoricidin,
licorisoflavan A, and licochalcone A have potential beneficial effects in human diseases
as reported in a large number of in vitro and in vivo studies (Kao et al. 2014).
Some side effects in humans have been reported due to liquorice intake, but all
seem to be reversible. Use of this herb or intake of its extract with proper control
fully supports its health benefits which clearly outweigh its side effects. Therefore,
before beginning the regular intake of any food or medicine with liquorice and its
related compounds, it is recommended that liquorice and the compounds isolated
from this herb can be used as a complement to aid current medicines to reduce/
eliminate side effects and improve the healing efficacy and outcome.
Recently the triterpene compounds of liquorice, such as glycyrrhizin and gly-
cyrrhetinic acid, have been studied at length for their various activities, like
anti-inflammatory, antitumor, antiviral, antidiabetic, immune-stimulating, and
hepatoprotective activities (Yang et al. 2015). The antiviral effects of glycyrrhizin
and glycyrrhetinic acid cannot be replaced by other compounds in liquorice, the
flavonoids, in particular, chalcones play an important role in the treatment of
cancer, inflammation, diabetes, and diseases caused by bacteria. The polysaccha-
rides from this plant have an effective and important function on enhancing
immunity. It is worth studying in detail (Yang et al. 2015).
Glycyrrhizin is stipulated in the Chinese Pharmacopoeia as one of the marker
compounds to evaluate the quality of this plant. Many other compounds have
shown excellent pharmacological activities so far, however, the quality evaluation
method needs to be updated to meet the need of clinical therapy (Yang et al. 2015).
The active ingredients and their proportion vary a lot in Glycyrrhiza uralensis,
Glycyrrhiza inflata, and Glycyrrhiza glabra (Simmler et al. 2014). On the other
hand, the differences in their clinical applications are infrequent. Even different
parts of this species, main roots, adventitious roots, and lateral roots, contain dif-
ferent levels of active ingredients. All these lead to differences in pharmacological
activities (Yang et al. 2015). The functional genes are involved in the biosynthesis
of metabolites. They finally lead to differences in a pesticide effect worth studying.
Liquorice extract also inhibits NO production and inducible nitric oxide synthase
expression in lipopolysaccharide-stimulated RAW264 murine macrophage cells.
The treatment with glycyrrhizin alone does not show this activity. The inhibitory
effect of the glycyrrhizin knockout extract has significantly been attenuated com-
pared with the extract. Combined treatment with glycyrrhizin knockout extract and
glycyrrhizin improves the attenuated inhibition (Uto et al. 2012). Some biological
activities may be due to the combined effects of several liquorice constituents rather
than a specific active ingredient. The future research direction could be a synergistic
activity (Yang et al. 2015). The clinical safety of this plant has been evaluated at
length, and there is apparently a great individual variation in the susceptibility to
11 Concluding Remarks and Future Directions of Research 137

glycyrrhizin and other compounds. A special strategy should be developed to

evaluate the possible adverse effects of this plant and multidose pharmacokinetics
should be characterized very well (Yang et al. 2015).

References

Costanza R, Farber S (2002) Introduction to the special issue on the dynamics and value of
ecosystem services: integrating economic and ecological perspectives. Ecol Econ 41:367–373
Farber S, Costanza R, Childers DL (2006) Linking ecology and economics for ecosystem
management. Bioscience 56:121–133
Kao T-C, Wu C-H, Yen G-C (2014) Bioactivity and potential health benefits of licorice. J Agric
Food Chem 62:542–553
Ozturk M, Gucel S, Altundag E, Celik S (2011) Turkish Mediterranean medicinal plants in the
face of climate change. In: Ahmad et al (eds) Medicinal plants in changing environment.
Capital Publishing Company, New Delhi, India, pp 50–71
Ozturk M, Gucel S, Altundag E, Mert T, Gork C, Gork G, Akcicek E (2012a) An overview of the
medicinal plants of Turkey. In: Singh R (ed) Genetic resources, chromosome engineering and crop
improvement: medicinal plants, vol 6. CRC Press, LLC, Taylor & Francis, USA, pp 181–206
Ozturk M, Kebapçı U, Gücel S, Çetin E, Altundağ E (2012b) Biodiversity and land degradation in
the lower Euphrates subregion of Turkey. J Environ Biol 33:311–323
Ozturk M, Gucel S, Celik A, Altundag E, Mert T, Akcicek E, Celik S (2012c) Myrtus communis in
phytotheraphy in the Mediterranean. In: Ram Singh (ed) Genetic resources, chromosome
engineering & crop improvement: medicinal plants, vol 6. CRC Press, LLC, Taylor & Francis,
USA, pp 923–934
Ozturk M, Altay V, Gucel S, Guvensen A (2014) Halophytes in the East Mediterranean-their
medicinal and other economical values. In: Khan et al (eds) Sabkha ecosystems vol IV cash
crop halophytes biodiversity & conservation. Tasks for vegetation science series, Springer,
NY, USA, pp 247–272
Ozturk M, Altay V, Altundağ E, Gucel S (2016) Halophytic plant diversity of unique habitats in
Turkey: Salt Mine Caves of Çankırı and Iğdır. In: Khan MA, Ozturk M, Gul B, Ahmed MZ
(eds) Halophytes for food security in dry lands. Elsevier. doi:http://dx.doi.org/10.1016/B978-0-
12-801854-5.00018-2
Ozturk M, Altay V, Gonenç TM (2017a) Herbal from High Mountains in the East Mediterranean.
In: Bhojraj S et al (eds) Drug discovery from herbs—approaches and applications. Centre for
Science & Technology of the Non-aligned and other Developing Countries (NAM S & T
Centre), DAYA Publishing House, New Delhi-India, pp 327–367. ISBN: 978-93-86071-46-0
Ozturk M, Altay V, Gucel S, Altundağ E (2017b) Plant diversity of the drylands in Southeast
Anatolia-Turkey: role in human health and food security. In: Ansari AA, Gill SS (eds) Plant
biodiversity: monitoring, assessment and conservation. CABI UK, pp 83–124
Simmler C, Jones T, Anderson JR, Nikolić DC, van Breemen RB, Soejarto DD, Chen SN,
Pauli GF (2014) Species-specific standardisation of licorice by metabolomic profiling of
flavanones and chalcones. Phytochem Anal 25:378–388
Svetlana AP, Atayevna MG, Ozturk M, Gucel S, Ashyraliyeva M (2012) An overview of the
ethnobotany of Turkmenistan and use of Juniperus turcomanica in phytotherapy. In: Singh RJ
(ed) Genetic resources, chromosome engineering, and crop improvement, vol 6. CRC Press,
Boca Raton, pp 207–220
138 11 Concluding Remarks and Future Directions of Research

Uto T, Morinaga O, Tanaka H, Shoyama Y (2012) Analysis of the synergistic effect of

glycyrrhizin and other constituents in licorice extract on lipopolysaccharide-induced nitric
oxide production using knock-out extract. Biochem Biophys Res Commun 417:473–478
Yang R, Wang LQ, Yuan BC, Liu Y (2015) The pharmacological activities of licorice. Planta Med
81(18):1654–1669
Index

A F
Anti-ulcer, 93, 135 Flavanoids, 46, 48
Avicenna, vii Flavonoids, 46, 47, 49, 53, 59, 60

B G
Biomass, 24–26, 28, 31–33, 130 Glycyrrhizin, 36, 37, 42, 46, 54, 61, 74, 78–82,
90–96, 99–103, 129, 130, 133, 134,
D 136, 137
Dementia, 45, 98, 135
S
Saponin, 46, 49, 54

© The Author(s) 2017 139

M. Öztürk et al., Liquorice, SpringerBriefs in Plant Science,
https://doi.org/10.1007/978-3-319-74240-3