A Pharmacognostic and Bibliometric Exploration of Glycyrrhiza Glabra: From Ancient Remedies To Modern Applications
A Pharmacognostic and Bibliometric Exploration of Glycyrrhiza Glabra: From Ancient Remedies To Modern Applications
Abstract: The plant Glycyrrhiza glabra L. (also known as licorice or "mulethi") has been historically used in both
therapeutic and nontherapeutic fashions, based on its unique phytochemical constituents, which subsequently resulted in
broad pharmacological activity and applications. This review documents G. glabra, from its various historical uses and
forms of traditions, taxonomy, and distribution, to its phytoconstituents and pharmacological activity (anticancer,
antiinflammatory, antioxidant, antimicrobial, and antidiabetic) substantiated by in-vitro and in-vivo work. This review
integrates bibliometric references and citations to illustrate the global interest of this plant; indeed, the significant interest
in G. glabra is reflected globally. Therapeutic value was demonstrated by the hydroalcoholic, methanolic, and aqueous root
extracts of G. glabra; therefore, these extracts are a viable candidate in drug discovery and development as
phytopharmaceuticals. Overall, this review on G. glabra integrates ancient medical traditions with modern pharmacological
science, support its use with integrative and evidence-based medicine.
Keywords: Glycyrrhiza Glabra, Licorice, Phytochemistry, Bioactive Compounds, Anticancer Activity Antioxidant, Anti-
Inflammatory, Antidiabetic, Antimicrobial, Traditional Medicine, Pharmacological Activities, Herbal Drug Discovery, Flavonoids,
Glycyrrhizin, Licorice Root Extract.
How to Cite: Sanjeet Kumar; Dr. Vinay Sen; Dr. Jasmeet Singh; Atreyee Mukherjee; (2025) A Pharmacognostic and Bibliometric
Exploration of Glycyrrhiza Glabra: from Ancient Remedies to Modern Applications. International Journal of Innovative Science
and Research Technology, 10(7), 745-768. https://doi.org/10.38124/ijisrt/25jul242
The image shows the dried root of Glycyrrhiza glabra, Taxonomical Description
more commonly called licorice or mulethi. The roots are Gigabar is an herbaceous perennial plant that has one
fibrous and cylindrical, light brown on the outside and meter in height. It has pinnate leaves that are seven to fifteen
yellowish on the inside, and readily available from a dry herb centimetres wide and have nine to seventeen leaflets (Sharma
supplier. The roots represent the chief harvest area of the et al., 2017). The lax inflorescence produces purple to pale
plant, and contain a large number of bioactive compounds greyish-blue flowers. The fruit is a 2–3 cm long, oblong pod
including glycyrrhizin, glabridin, and flavonoids, making with many seeds (Batiha et al.,2020). The pea-family shrub
them useful in all the traditional medicine systems such as Glycyrrhiza thrives in subtropical areas with fertile soil
Traditional Chinese Medicine, Unani, and Ayurveda, as an (Sharma et al.,2017). The Glycyrrhiza glabra plant has a large
anti-inflammatory, anticancer, antimicrobial, and antidiabetic underground root system that includes many runners and the
agent. major taproot (Jia et al.,2024). The primary taproot is soft,
fibrous, and has a bright yellow interior; it is gathered for
There are more than 30 species of Glycyrrhiza genus medicinal purposes (Dastagir et al., 2016).
extensively spread worldwide (Rizzato et al., 2017). It has
been planted since the 16th century in Europe. It was the most II. TRADITIONAL USES OF G. GLABRA
prescribed herb in Ancient Egyptian, Roman, Greek, East
China, and the West from the Former Han era (Shibata et Licorice has been known to be used in traditional
al.,2000). Various species of licorice are cultivated in Europe, pharmacopoeia for asthma, tonsillitis, sore throats, thirst,
the USA, South-Western Asia and Central Africa, the Middle excessive gas in the GI tract, epilepsy, fevers, sexual debility,
East, Afghanistan, and the North part of India. In addition, paralysis, coughs, peptic ulcers, heartburn, colic,
England, Spain, Iraq, Turkey, China, and Sicily commercially inflammation, rheumatism, skin infections, acid regulation,
cultivate licorice (Tohma et al.,2010) [18]. Other countries leucorrhea, haemorrhage, haemorrhagic pathologies,
producing the licorice are Pakistan, Azerbaijan, Turkmenistan jaundice, etc. (Khare et al., 2024, Damle et al., 2014, Kaur et
and Uzbekistan. al., 2013). Also, licorice has been used in a field as
insecticide, laxative, anti-inflammatory, anti-ulcer, antibiotic,
anti-arthritic, antagonist in relaxant, antivirals, stimulate or
improve in memory, anticholinergic, anti-tussive, anti-caries,
This number depicts a broad suite of bioactive This figure illustrates glycosidic compounds from
compounds separated from Glycyrrhiza glabra (licorice) from licorice, including liquorice glycosides A-C2, violanthin,
a number of different classes including flavonoids (e.g., isoviolanthin, and fujikinetin derivatives. These compounds
liquiritin, isoliquiritin, isoflavones (e.g., formononetin, consist of flavonoid backbones that have sugar moieties
daidzein), and triterpenoids (e.g., glycyrrhizin, glabrol). They conjugated to them. During the conjugation of sugar moieties,
show multifaceted pharmacological properties including anti- there is an increase in their solubility in water and
inflammatory, antioxidant, antidiabetic, hepatoprotective, bioavailability. The glycosides are critical to the medicinal
and antimicrobial activities, and the structural diversity effects in antioxidant and immunomodulatory responses that
typically encountered helps explain the diversity in biological support the adaptogenic aspects of licorice.
actions attributed to licorice.
The picture illustrates structurally diverse prenylated flavonoids, isoflavonoids, and coumarins with structural likeness to
glyasperin D, semilicoisoflavone B, and licoaryl coumarin. It is intended the prenyl or methoxy groups improve the permeability
and the membrane bioactivity of these structures. All these compounds bear anti-inflammatory, estrogenic, and anti-cancer activities;
but there is potential therapeutic modality for thyroid benefit.
Fig 6 Rare and Complex Flavonoid Derivatives from Licorice Species Description:
This figure shows only rare flavonoid analogs (i.e., neuroprotective, cytoprotective activities. These secondary
kanzonol C, kuwanon V, parvisoflavone A, and 6,8- metabolites illustrate the phytochemical richness and
diprenylgenistein) with polyphenolic scaffolds and prenyl ethnomedicinal potential of Glycyrrhiza species.
modifications that offered enhanced antimicrobials,
This table lists the various bioactive compounds emphasizes the wide chemical diversity, including
isolated from Glycyrrhiza glabra, along with their molecular flavonoids, chalcones, saponins, and phenolics.
formulas, molecular weights (MW), and references. The data
This table provides the chemical profiling of G. glabra Cancer is an extremely heterogeneous disease
root extracted with methanol. It includes volatile and non- characterized by pathological cell growth, proliferation and
volatile compounds primarily identified through analytical metastasis of neoplastic cells. Cancer is also one of the
techniques such as GC-MS. leading causes of death in the world. Cancer treatment can
involve multiple modalities, including surgical excision,
III. ANTICANCER ACTIVITY radiation therapy, immunotherapy, targeted agents, and
chemotherapeutics; however, most of the world refers to
Cancer is defined by the formation, proliferation, and chemotherapeutics as 'pain killers.' The use of
distribution of abnormal cells in the human body and one of chemotherapeutic agents may be associated with many
the leading causes of global deaths. All of the surgical adverse reactions both common and severe, and may disrupt
procedures, chemotherapy, surgery, radiation therapy, and bodily function via non-specific cytotoxicity as they kill
other techniques involved when used by oncologists is known normal growing cells just as malignant cells, including
as cancer therapy. Chemotherapy is the most recognized healthy cells.
therapy. Chemotherapy medications are known to have a
variety of side effects, such as loss of hair, anaemia, Given all of that, there has been a resurgence of interest
gastrointestinal toxicities, and immunosuppression. These in foods to produce healthy compounds from plant sources,
side effects occur because chemotherapy medications are not with an anti-cancer agent which has little host toxicity or
only killing abnormal cancer cells rapidly growing cells, but specificity. Gly(prof Ace(locice) has been known for its
also harming normally functioning cells. Isolated medicinal properties for hundreds of hundreds of years, and
Lichoflavonons from G. glabras leaf can inhibit breast cancer is one of the ideal candidates for anti-can-cer drugs, primarily
cell lines like MCF-7, MDA-MB 231, and MCF-10A at an because of the variability in phytotherapy.
inhibitory concentration (IC50) 19.18, 10.97, and
41.38µm/ml (Frattarulo et al., 2024). In another study, IV. MECHANISTIC PATHWAYS
Sharma et al., 2017 isolated 12 phytocompounds from the
root of G. glabra, and only the quercetin and glabrols had ic50 Anticancer Mechanisms
values of 2.2 and 15 mM/ml for triple-negative MDA-MB-
468 breast cancer cells. Caspase-mediated apoptosis Induction:
Many plant-based chemicals are believed to stimulate
Cancer is a heterogeneous disease caused by aberrant caspase-3, the primary mediator of apoptosis and the
cell growth, proliferation, and metastasis of neoplastic cells. mediator of typical programmed death of cancer cells.
In addition, it is one of the leading causes of death globally.
There are multiple options for treating cancer including p53 tumor suppressor induction:
surgical excision, radiation, immunotherapy, targeted agents, Activation of p53 causes cells to arrest in their cell cycle
and chemotherapeutics; however, most people sometimes to repair rather than die, which is an option for damaged cells.
refer to chemotherapeutics as "pain killers". Chemo agents
can have many adverse reactions, common and serious, and Bcl-2 family modulation:
occasion disruption of bodily function via non-specific Natural products would typically downregulate an anti-
cytotoxicity because they kill healthy growing cells just like apoptotic Bcl-2, and upregulate the pro-apoptotic Bax, both
malignant cells, even healthy. With all of these facts in mind, of which influence mitochondrial outer membrane
there is renewed interest in using healthy compounds from permeability (MOMP).
plant sources, with an anti-cancer agent with little host
toxicity or specificity. Gly(prof Ace(locice) has been known ROS-mediated mitochondrial pathway. However, if the
for its medicinal properties for hundreds of years, and is a signaling in the humoral arm does promote an excess of
prime candidate for anti-cancer drugs because of the diverse reactive oxygen species (ROS), the events cease being
phytochemistry. humoral, and common downstream events occur such as
mitochondrial dysfunction, cytochrome c release from the
Phytochemical Information and in Vitro Tests inner membrane space, and the induction of a caspase-
Lichoflavonons, which have been purified from the mediated intrinsic apoptotic response.
leaves of G. glabra, demonstrate significant cytotoxicity
towards breast cancer cell lines MCF-7, MDA-MB-231, and
MCF-10A. The IC₅₀ values were observed as 19.18, 10.97,
and 41.38 µM/mL, suggesting a dose-dependent anticancer
activity (Frattarulo et al., 2024).
The figure depicts multiple key molecular pathways in Changes in the family of Bcl-2: inhibition of the anti-
which bioactive constituents, including constituents in apoptotic Bcl-2 protein and induction of pro-apoptotic Bax
Glycyrrhiza glabra, exhibit anticancer activity: proteins changed the Bcl-2 family of proteins and
mitochondrial MOMP potential to support apoptosis.
Apoptosis via caspase activation: Phytochemicals
activated caspase-3, which knife e, made the participants into Intrinsic mediated ROS signaling pathway: increases in
the previously detected functional state used to identify itself reactive oxygen species (ROS) caused mitochondrial
as the effector protease of programmed cell death (apoptosis) dysfunction and release of cytochrome c that led to intrinsic
for cancer cells. mediated apoptosis signaling
This table summarizes in vitro anticancer studies liver detoxification and hypertension that require monitoring
performed using various G. glabra extracts. It details the (Sarfaraz et al., 2013).
plant part, extract method, cancer cell line targeted, and
reference. VI. MOLECULAR MECHANISMS OF ACTION
Inhibition of NF-κB Signaling: Many phytoconstituents Activation of Nrf2/HO-1 Axis: Some phytochemicals
inhibit the activation of nuclear factor kappa-light-chain- exert anti-inflammatory effects by activating Nrf2, which
enhancer of activated B cells (NF-κB), a key transcription upregulates heme oxygenase-1 (HO-1), an enzyme with
factor responsible for the expression of pro-inflammatory cytoprotective and anti-inflammatory functions.
cytokines like TNF-α, IL-1β, and IL-6.
Preclinical and Clinical Evidence
Suppression of COX and LOX Pathways: Bioactive In a study by Kobayashi et al. (2009), licorice extracts
compounds suppress the expression or activity of significantly reduced synovial inflammation in rheumatoid
cyclooxygenase (COX-1 and COX-2) and lipoxygenase arthritis (RA) animal models by suppressing leukocyte
(LOX) enzymes, thereby reducing the synthesis of infiltration and cytokine production.
inflammatory mediators such as prostaglandins (PGE2) and
leukotrienes. Al-Harbi (2014) demonstrated that licorice mitigated
intestinal inflammation in models of inflammatory bowel
MAPK Pathway Modulation: Certain phytochemicals disease (IBD), attributed to modulation of intestinal epithelial
modulate mitogen-activated protein kinase (MAPK) barrier integrity and downregulation of NF-κB activity.
signaling (including ERK, JNK, and p38), which controls the
production of cytokines and inflammatory enzymes. Additionally, G. glabra has shown efficacy in allergic
Inhibition of iNOS Expression: Many compounds and autoimmune inflammation, indicating its potential as a
downregulate inducible nitric oxide synthase (iNOS), complementary therapeutic agent.
This table compiles studies on anti-inflammatory chemotherapy, nutrition, contaminants, cigarette smoking,
potential, listing plant parts, extraction techniques, and along other similar activities are examples of external
references. It reflects the bioefficacy in treating arthritis, contributors to oxidants. At the other hand, internal sources
inflammatory bowel disease, etc. of oxidants include rigorous physical activity, infection, and
inflammatory disorders, along with the natural process of
Antioxidant aging (Finkel, 2000). Oxidants are accountable for an
Oxidative stress occurs when there are an excess or extensive range of people's diseases, including stroke,
deficit of oxidants (reactive nitrogen species, reactive oxygen hemochromatosis, cancer, osteoarthritis, neurological
species, and free radicals) and antioxidants (antioxidants). An disorders, and autoimmune disorders, among others.
excess or deficit can harm cells, tissues, and or organs. Free However, even at minimal and moderate levels, oxidants
radicals are extremely reactive moieties because they have contribute to the maturing of the structures of cells and
unpaired electrons (having an uneven number of electrons); improve the body's defenses against infectious organisms
therefore, they react with those other moieties that they (Pham-huy et al. 2008; Chandan et al. 2012). Antioxidants
surround. The sum of those free radicals acts as either an that are derived from plant-based sources are starting to
electron donor or acceptor depending the ownership of free receive the highest interest worldwide because of their
electrons. The predominately identified oxidants are, capacity to eliminate free radicals while simultaneously
according to Sies (1997): superoxide anion, hypochlorite, reducing the amount of risk associated with unwanted effects.
hydrogen peroxides, peroxynitrite, nitric oxide, and singlet
oxygen. Oxidants can alter, transform, and modify the target Mechanistic Pathways:
a biological entity such as protein, carbohydrate, lipid, or
DNA (Halliwell 2007). Antioxidant Mechanisms
Nrf2 Pathway Activation: Natural antioxidants activate
They are produced as byproducts of a wide variety of nuclear factor erythroid 2-related factor 2 (Nrf2), which
biological processes that may begin via external or internal translocates to the nucleus, binds to antioxidant response
factors. The radiation exposure (including x-rays, sunlight, elements (AREs), and activates transcription of phase II
ultrasound imaging, and microwaves), treatment such as
Fig 8 This Figure shows the main Antioxidant Pathways that Phytochemicals have done, and the
Protective effects in Oxidative Injury:
Covers studies assessing antioxidant capacity, reflecting oxidative stress reduction through extracts derived from various parts
and solvents.
VII. ANTIMICROBIAL
Cell Membrane Disruption: Essential oils, alkaloids, Disruption of Cell Membrane: As mentioned
and saponins interact with microbial lipid bilayers, increasing previously, many phytochemicals, especially essential oils,
membrane permeability, causing leakage of intracellular alkaloids and saponins attack the permeability of microbial
contents, and resulting in cell lysis. lipid bilayer membranes disrupting membrane permeability
leading to leaking of cellular contents and eventually lysis.
Inhibition of Nucleic Acid Synthesis: Flavonoids and
polyphenols bind to microbial DNA or inhibit DNA Inhibition of Nucleic Acid Synthesis: Some plant
gyrase/topoisomerase enzymes, effectively blocking polyphenols and flavonoids have a high affinity for microbial
replication and transcription processes. DNA gyrase/topoisomerase binding or activity and prevent
the replication and transcription of DNA.
Protein Synthesis Inhibition: Bioactive compounds
affect microbial protein synthesis by targeting the ribosome Inhibition of Protein Synthesis: bioactives can inhibit
(30S or 50S) subunits specifically and inhibiting their ability microbial ribosomes (30S or 50S) because they inhibit
to 'translate' and function. microbial ribosomal subunits thereby disrupting translational
activity and preventing protein synthesis.
Enzyme System Inhibition: Some phytocompounds
inhibit microbial enzyme systems by inhibiting dihydrofolate Inhibition of Enzyme Systems: Certain
reductase, ATPase or β-lactamase inhibiting needed pathways phytocompounds, such as dihydrofolate reductase, ATPase,
and/or their resistance to antibiotics. or β-lactamase, inhibit microbial enzymes, disrupting
metabolic processes or conferring resistance to β-lactam
Quorum Sensing Interference: Phytochemicals also antibiotics.
interfere with a bacteria's communication pathways,
inhibiting quorum sensing and biofilm formation and live by Quorum Sensing Interference: Compounds derived
inhibiting the intended expression of virulence factors. from plants have been reported to interfere with quorum
sensing signals, hindering bacterial communication, biofilm
Metal Ion Chelation: Many polyphenols chemate formation, and expression of virulence factors.
essential metal ions like Fe²⁺, Zn²⁺, Mg²⁺ preventing bacteria
from utilizing these essential metal ions, which are cofactors Metal Ion Chelation: Some polyphenols chelate Fe²⁺,
for the function of microbe’s enzyme and ability to replicate. Zn²⁺, and Mg²⁺, which are important cofactors for enzymatic
action of bacteria. ROS Generation: Some phytochemicals
ROS production: An increased level of oxidative stress can exert oxidative stress on microbes by promoting the
on microbes can be induced by some compounds by formation of reactive oxygen species (ROS), which can
producing reactive oxygen species (ROS), which can damage proteins, lipids, and DNA.
Acetate,
Tetrahydrofuran,
Toluene And N-
Hexane
16. Root Aqueous Staphylococcus aureus Escherichia coli Kim et al,2023
Details the antimicrobial spectrum of G. glabra extracts Enhancement of Insulin Sensitivity: Certain bioactives
against a range of bacterial and fungal pathogens, including activate PI3K/Akt signaling, promoting GLUT4 translocation
Staphylococcus aureus, E. coli, and Candida albicans. and glucose uptake in peripheral tissues.
Summarizes studies showing the anti-diabetic efficacy However, the therapeutic utilization of licorice must be
of compounds like glabridin, glycyrrhizin, and 18β- approached with caution due to its potential side effects,
glycyrrhetinic acid, in both in vitro and in vivo models (rat, particularly in cases of excessive or prolonged consumption,
mice, HepG2 cells). which may result in hypertension, hypokalemia, or hormonal
imbalances. This calls for more targeted clinical studies,
IX. CONCLUSION precise standardization of extract dosages, and robust safety
profiling.
Glycyrrhiza glabra, or licorice or mulethi, represents the
relationship of historical traditional medicine and In essence, Glycyrrhiza glabra is not merely a relic of
pharmacology knowledge. Investigating the pharmacognostic ancient pharmacopoeias but a dynamic, evolving resource in
properties, phytochemistry, and therapeutic efficacy of G. the field of natural product drug discovery. Future
glabra resulted in it being a multipurpose natural product for interdisciplinary research integrating molecular biology,
biomedical uses. The relationship of G. glabra as an active phytochemistry, clinical pharmacology, and bioinformatics is
pharmaceutical product and its potential obtained more essential to unlock its full pharmacological spectrum and
decades of awareness of a product of G. glabra and unique ensure its safe, sustainable, and efficacious integration into
applications of the plant in formulations for Ayurvedic and modern medicine.
Traditional Chinese Medicine and it potentially became a
viable active pharmaceutical novel drug development; a BIBLIOMETRIC ANALYSIS OF GLYCYRRHIZA
historical link has paved unique relationship as a treatment of GLABRA LITERATURE
many similar conditions.
Interpretation:
The plant’s phytoconstituent richness—encompassing The consistently growing citation trend and robust H-
flavonoids, isoflavones, chalcones, glycosides, and index value underscore the scientific relevance and
triterpenoid saponins—underlies its broad-spectrum pharmacological significance of G. glabra. The
pharmacological efficacy. Notably, compounds such as predominance of original research articles (83%) highlights
glycyrrhizin, glabridin, licochalcone A, and isoliquiritigenin active experimental investigations into its therapeutic
exhibit potent anticancer, anti-inflammatory, antioxidant, properties, while the increasing number of reviews and early
antimicrobial, and antidiabetic properties through well- access articles signals sustained scholarly interest and
elucidated mechanisms including modulation of emerging discoveries.
PI3K/Akt/NF-κB signaling, apoptosis induction, ROS
scavenging, enzyme inhibition, and enhanced glucose uptake. This bibliometric profile solidifies Glycyrrhiza glabra
as a prominent herbal candidate in modern biomedical
In vitro and in vivo studies confirm the therapeutic research, encouraging future exploration in drug discovery,
potential of different extracts from licorice root, leaf, and bioactive isolation, and clinical evaluation.
rhizome: aqueous, methanolic, ethanolic, and hydro-
alcoholic. Clinical relevance is circumscribed by bibliometric Total Publications (1989–2025): 535
figures which demonstrate an increasing level of global
interest into G. glabra as phytopharmecuetical.Reliance on Total Citations: 4,807
past ethnomedicinal experience, combined with modern
experimental studies, demonstrates promise in G. glabra as a Without Self-Citations: 4,353
possible candidate for integrative therapeutic approaches,
particularly as a potential agent to manage complex chronic Average Citations per Item: 8.99
ailments such as cancer, diabetes, and autoimmune diseases.