Food Chemistry: X 13 (2022) 100217

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Food Chemistry: X
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Terpenes and terpenoids as main bioactive compounds of essential oils,

their roles in human health and potential application as natural
food preservatives
Ayu Masyita a, Reka Mustika Sari b, c, Ayun Dwi Astuti a, Budiman Yasir a, d, Nur Rahma Rumata d,
Talha Bin Emran e, *, Firzan Nainu a, *, Jesus Simal-Gandara f, *
a
Faculty of Pharmacy, Hasanuddin University, Makassar 90245, Sulawesi Selatan, Indonesia
b
Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Sumatera Utara, Medan 20222, Sumatera Utara, Indonesia
c
Cellulosic and Functional Materials Research Centre, Universitas Sumatera Utara, Jl. Bioteknologi No.1, Medan 20155, Indonesia
d
Sekolah Tinggi Ilmu Farmasi Makassar, Makassar 90242, Sulawesi Selatan, Indonesia
e
Department of Pharmacy, BGC Trust University Bangladesh, Chittagong 4381, Bangladesh
f
Universidade de Vigo, Nutrition and Bromatology Group, Department of Analytical Chemistry and Food Science, Faculty of Science, E32004 Ourense, Spain

A R T I C L E I N F O A B S T R A C T

Keywords: Essential oils (EOs) are volatile and concentrated liquids extracted from different parts of plants. Bioactive
Essential oil compounds found in EOs, especially terpenes and terpenoids possess a wide range of biological activities
Anticancer including anticancer, antimicrobial, anti-inflammatory, antioxidant, and antiallergic. Available literature con­
Antimicrobial
firms that EOs exhibit antimicrobial and food preservative properties that are considered as a real potential
Anti-inflammatory
Food preservatives
application in food industry. Hence, the purpose of this review is to present an overview of current knowledge of
Terpenes EOs for application in pharmaceutical and medical industries as well as their potential as food preservatives in
Chemical compounds studied in this article:
food industry.
Carvacrol (PubChem CID: 10364)
Linalool (PubChem CID: 6549)
Hinokitiol (PubChem CID: 3611)
Bakuchiol (PubChem CID: 5468522)
Limonene (PubChem CID: 22311)
Eugenol (PubChem CID: 3314)
Myrcene (PubChem CID: 31253)
α-Terpineol (PubChem CID: 17100)
Atractylone (PubChem CID: 3080635)
Carvone (PubChem CID: 7439)

Introduction 2020), antihelminthic (Inouye, Takizawa, & Yamaguchi, 2001), anti­

viral (Silva, Figueiredo, Byler, & Setzer, 2020), antiulcer (Dordević
The notion to promote the use of natural products in daily life have et al., 2007), antioxidant (Falleh et al., 2020; Mimica-Dukić, Bozin,
spread worldwide in the last several decades. Of all, essential oils (EOs) Soković, Mihajlović, & Matavulj, 2003), anti-inflammatory (Silva et al.,
have been one of the most utilized natural products (Carpena, Nuñez- 2015), insecticide (Isman & Machial, 2006), larvacidal (Jantan, Ping,
Estevez, Soria-Lopez, Garcia-Oliveira, & Prieto, 2021). Essential oils are Visuvalingam, & Ahmad, 2003), immunomodulatory (Mediratta,
highly concentrated hydrophobic liquid derived from a variety of plants Sharma, & Singh, 2002), and antinociceptive properties (Abdollahi,
and defined based on their chemical and physical properties. The Karimpour, & Monsef-Esfehani, 2003).
pharmacological effect of EOs have been extensively examined: ranging Essential oils have long been used as flavorings in the food industry
from antimicrobial (Burt, 2004; Falleh, Ben Jemaa, Saada, & Ksouri, (Pandey, Kumar, Singh, Tripathi, & Bajpai, 2017). Of thousands

* Corresponding authors.
E-mail addresses: [email protected] (T.B. Emran), [email protected] (F. Nainu), [email protected] (J. Simal-Gandara).

https://doi.org/10.1016/j.fochx.2022.100217
Received 31 October 2021; Received in revised form 8 January 2022; Accepted 14 January 2022
Available online 19 January 2022
2590-1575/© 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
A. Masyita et al. Food Chemistry: X 13 (2022) 100217

Fig. 1. The potential benefits of terpenes and terpenoids found in EOs.

different EOs known at present, around 300 are commercially marketed applications of EOs’ constituents in the daily life.
in the flavor and fragrances products (Hyldgaard, Mygind, & Meyer,
2012). In addition to their aromatic qualities, the antimicrobial prop­ Bioactive compounds of essential oils
erties of EOs against a wide range of microorganisms have also provided
convincing evidence that EOs are suitable candidates to be used as Essential oils are concentrated liquids of complex mixtures of aro­
natural food preservatives (Falleh et al., 2020). Among all chemical matic hydrophobic oily volatile compounds and can be extracted from
components of EOs, terpenes and terpenoids have been comprehensively different parts of plants such as bark, buds, flowers, fruits, leaves, peels,
studied and reported to play key roles in humans health (Perveen, roots, seeds, twigs, or whole plant from a single botanical source (Falleh
2018). et al., 2020; Stephane & Jules, 2020). International Organization for
Terpenes (pinene, myrcene, limonene, terpinene, p-cymene) are Standardization (ISO) defines that EOs are products obtained from raw
characterized as compounds with simple hydrocarbons structures while material of vegetables by pressing or distillation processes (Stevanovic,
terpenoids (oxygen-containing hydrocarbons) are defined as modified Sieniawska, Glowniak, Obradovic, & Pajic-Lijakovic, 2020).
class of terpenes with different functional groups and oxidized methyl Essential oils possess a strong odor and usually colorless especially
groups moved or removed at various positions (Perveen, 2018). Ter­ when fresh, but some exceptions are known such as pale yellow (yellow
penes have been reported to exert antimicrobial activities against both mandarin), blue (chamomile), orange (sweet orange), and green
the antibiotic-susceptible and antibiotic-resistant bacteria, mainly via (bergamot). EOs may be easily oxidizable with age by air, heat, or light
their abilities to promote cell rupture and inhibition of protein and DNA exposure which proceed to the dark color. Hence, EOs need to be stored
synthesis (Álvarez-Martínez, Barrajón-Catalán, Herranz-López, & Micol, in a cool and dry place (Stephane & Jules, 2020). Structurally, the
2021). Carvacrol, carvone, eugenol, geraniol, and thymol were among chemical constituents of EOs can be classified into four groups: terpenes,
the terpenes that demonstrated antibacterial action against Staphylo­ terpenoids, phenylpropanoids, and other constituents (Hyldgaard et al.,
coccus aureus (Gallucci et al., 2009). In addition, terpenoids have been 2012; Pandey et al., 2017).
shown as one of secondary metabolites produced by aromatic and me­
dicinal plants that played a key role in disease resistance. For example, Terpenes
monoterpenoids are antibacterial in nature, causing disruption in
microbe multiplication and development, as well as interfering with Terpenes or isoprenoids are the major constituents found in EOs with
their physiological and metabolic activities (Burt, 2004). Some botanical molecular structures containing carbon backbones of 2-methylbuta-1,3-
compounds, such as azadirachtin, carvone, menthol, ascaridol, methyl diene (isoprene units) which can be rearranged into cyclic structures
eugenol, toosendanin, and volkensin, have been shown to yield anti­ (Hyldgaard et al., 2012). The number of isoprene units are primarily
microbial and antifungal properties, as well as insect pest repellent responsible for structural diversity of terpenes. Hemiterpenes are
properties (Isman & Machial, 2006; Pandey et al., 2016, 2017). formed by one isoprene unit (C5), monoterpenes (C10), sesquiterpenes
In addition to their various pharmacological effects in humans, the (C15), diterpenes (C20), triterpenes (C30), and tetraterpenes (C40)
antimicrobial capabilities of EOs’ terpenes and terpenoids against (Bhavaniramya, Vishnupriya, Al-Aboody, Vijayakumar, & Baskaran,
foodborne microbes and their beneficial use in food as flavoring addi­ 2019). Hemiterpenes are a minor part of terpenes found in EOs. The
tives shall serve as excellent alternatives to the standard bactericides and most outstanding HT, isoprene which is emitted from the herbs and
fungicides currently used in the food industry (Perricone, Arace, Corbo, leaves of many trees such as conifers, oaks, poplars, and willows. Ex­
Sinigaglia, & Bevilacqua, 2015). This review will thus provide an amples of hemiterpenes include angelic, tiglic, isovaleric, and senecioic
overview to the current knowledge about the potential role of terpenes acids. Monoterpenes are the predominant components of EOs (90%),
and terpenoids, as main bioactive compound of EOs, in human health followed by sesquiterpenes (Falleh et al., 2020). Diterpenes, triterpenes,
and their industrial potential as natural food preservatives (Fig. 1). This, and tetraterpenes with their oxygenated derivatives are also detected in
in turn, shall provide prompt opportunities to cultivate more and better small amounts (Stephane & Jules, 2020). Examples of bioactive com­
ideas and research avenues that can promote extensive pharmaceutical pounds of EO are presented in Fig. 2.

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A. Masyita et al. Food Chemistry: X 13 (2022) 100217

Fig. 2. The chemical structures of bioactive compounds of EOs.

Terpenoids linalool, linalyl acetate, piperitone, menthol, and thymol (Hyldgaard

et al., 2012). These bioactive compounds confer several biological ac­
Terpenoids are another type of terpenes containing oxygen mole­ tivities such as anticancer (Potočnjak, Gobin, & Domitrović, 2018), anti-
cules that are constructed via biochemical modifications (removal or allergic (Kobayashi et al., 2016), antibacterial (Guimarães et al., 2019),
addition of methyl groups) (Pandey et al., 2017). Terpenoids can be and antioxidant (Wang, Chen, & Hou, 2019).
divided into alcohols, aldehydes, esters, ether, epoxides, ketones, and Terpenes and terpenoids are synthesized by the mevalonic acid
phenols. Examples of terpenoids are: carvacrol, citronellal, geraniol, (MVA) pathway in the cytosol and the 2C-methyl-D-erythritol-4-

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A. Masyita et al. Food Chemistry: X 13 (2022) 100217

phosphate (MEP) pathway in the plastid for the formation of precursors: polar solvents including acetone, aqueous methanol (80%), and ethanol,
isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate followed by re-extraction with hexane, chloroform, and ethyl acetate,
(DMAPP) (Oldfield & Lin, 2012; Stephane & Jules, 2020). resulted in sequential extraction of terpenoids. Whereas, modern
methods include supercritical carbon dioxide extraction, static head­
Phenylpropanoids space (HS) extraction, microwave-assisted hydrodistillation (MWHD),
supercritical fluid extraction (SFE) and ultrasound-assisted extraction
Phenylpropanoids are synthesized by the shikimic acid pathway and (UAE). Supercritical fluid extraction (SFE) with carbon dioxide as the
their basic structure from the six-carbon aromatic phenol group linked solvent is considered a “green extraction” method in comparison to
usually to the three-carbon propene tail of cinnamic acid, oxygenated in traditional extraction methods because it uses a solvent that is essen­
the third/fourth/fifth position frequently possess a carbon–carbon tially non-toxic, has a low potential for artifact formation, and CO2 can
double bond (Stevanovic et al., 2020). Examples of phenylpropanoids be obtained in high purity suitable for the production of food grade
such as anethole, cinnamaldehyde, eugenol, isoeugenol, myristicin, extracts. The inclusion of polarity modifiers such as EtOH, as well as the
safrole, and vanillin. In a recent study, anethole has been reported to development of SFE apparatus capable of producing pressures in excess
yield anticancer activity (Contant, Rouabhia, Loubaki, Chandad, & of 600 bar, enabled the extraction of several intermediate polarity
Semlali, 2021). Moreover, myristicin has been described to exert anti­ compounds (Essien, Young, & Baroutian, 2020). UAE was useful for the
proliferative and anti-inflammatory properties (Seneme, Dos Santos, green production of solvent-free terpenoid-rich peppermint extracts.
Silva, Franco, & Longato, 2021) and safrole has been reported to pro­ MWHD is better than traditional techniques since it requires fewer
mote diverse biological activities, such as antidiabetic, antimicrobial, extraction times and less solvent. It operates at atmospheric pressure,
analgesic, and antifungal activities (Eid & Hawash, 2021). utilizing microwaves and gravity without solvents (Pavlić et al., 2021).
Furthermore, recent report suggested that HS was the most efficient
Other constituents extraction method to recover terpenoids from various food matrices,
compared to hydrodistillation and pressurized liquid extraction (Triaux,
EOs contain several derivatives of amino acids such as alanine, Petitjean, Marchioni, Steyer, & Marcic, 2021). Compound extraction
isoleucine, leucine, valine, and methionine. Polyketides, lipids, and generates a complicated mixture of compounds. Specific compounds are
sulfur derivatives are rarely found in EOs such as jasmonic acid, methyl now isolated using purification methods. Purification procedures varies
jasmonate, cis-jasmone, (Z)-3-hexenal, allicin (Pandey et al., 2017; due to variations in terpene and terpenoids structure, and they are
Stevanovic et al., 2020). depending on the chemical characteristics of the target molecule, the
physical quality and amount of initial plant material, and the avail­
Green extraction and purification methods of terpenes and ability of equipment and reagents. The properties of a particular terpene
terpenoids will define the optimum extraction method (Yang et al., 2020; Zhang &
Hong, 2020). This is followed by compound identification, character­
Extraction is the most essential stage in extracting and purifying ization, and authentication namely Thin Layer CT (Chromatostrip),
active compounds from natural sources. Natural chemicals can be High-Performance Counter-Current Chromatography (HPCCC), Liquid-
extracted via maceration, infusion, soxhletation, percolation, or Liquid Extraction (LLE), High Performance Liquid Chromatography
digesting methods (Giacometti et al., 2018). Due to growing energy UV (HPLC-UV), Gas Chromatography Mass Spectrometry (GC–MS),
prices, CO2 emissions, and other associated environmental issues, Liquid Chromatograph (LC), High Performance Thin Layer Chroma­
extraction techniques for the chemical, food, and pharmaceutical sectors tography (HPTLC), Fast-GC Analysis and Ultra-High-Performance Liquid
have received much interest in recent years. One of the most popular Chromatography (UHPLC) (Rodríguez-Llorente et al., 2020; Uwineza &
topics in this approach is the development of methods and procedures to Waśkiewicz, 2020).
achieve maximal extraction at a low cost and in an environmentally
friendly. In general, the methods involve the following steps (Fig. S2, Role of terpenes and terpenoids on human health
Supplementary material): (a) breaking plant cells to release their
chemical constituents; (b) extracting the sample using a suitable sol­ In recent decades, numerous studies have reported that terpenes and
vent—or through distillation or compound trapping; (c) separating the terpenoids are essential in supporting human health. These bioactive
desired terpene from undesired contents of extracts that confound compounds consisting of several isoprene units is the largest class of
analysis and quantification; and (d) analyzing the product using an organic compounds produced in the EOs of various plants. It has a sig­
appropriate method (Asl & Khajenoori, 2021). nificant role to treat various types of diseases, in many studies in vitro
In this chapter, the processes in isolation of terpene and terpenoid and in vivo using as anticancer agents, antimicrobial, anti-
chemicals in plants and the technique of determining structure eluci­ inflammatory, antioxidants, antiallergic, neuroprotective, anti-
dation were presented (Fig. S3, Supplementary material). The pre- aggregator, anti-coagulation, sedative and analgesic through the activ­
treatment stage is the most time-consuming. This stage is determined ity of monoterpenes, sesquiterpenes, diterpenes, triterpenes, and tetra­
by the physical condition of the sample, which might be solid or liquid. terpenes and glycoside compounds (Zhao, Jiang, Li, Yan, & Zhang,
Several techniques are employed to decrease the size of the solid sample, 2016). The content of this compound can be found in several nutritional
including steaming, dry distillation, and heating, which is subsequently and health products of humans because it is a source of vitamins A, E, K,
milled. For liquid samples, another option is to employ solvent treat­ and coenzyme Q10. Even carotenoid and tocopherol compounds in this
ment or chemical treatment. This method is critical in sample prepara­ group are essential sources of vitamins, mostly in animals, including
tion to improve extraction efficiency. Traditional terpene and terpenoids humans (Rodriguez-Concepcion et al., 2018). The application of ter­
extraction methods include maceration, soxhlet extraction, solvent penes compounds in everyday human life and health is widely used in
extraction, pressurized liquid extraction, and hydrodistillation (Isidore, pharmaceutical, nutraceutical, food and beverage products, cosmetics,
Karim, & Ioannou, 2021). Solvent extraction used such as petroleum perfumes, synthetic chemicals, aroma and flavor additives, rubber
ether, ether, and hexane for isolating mono and sesquiterpenoids. Less products, and the biofuel industry (Tetali, 2019).
polar sesquiterpene lactones, diterpenes, sterols, and triterpenoids may
also be extracted using ether and chloroform. Oxygenated diterpenoids, Anticancer
sterols, and triterpenoids are found in the ethyl acetate and acetone
extracts. Highly oxygenated, polar triterpenes, as well as triterpenoid, Cancer is a regenerative disease that affects anybody part’s abnormal
are extracted using ethanol, methanol, and water. Total extraction using and uncontrolled cell growth. It can attack or spread to various other

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A. Masyita et al. Food Chemistry: X 13 (2022) 100217

Table 1
Examples of terpene compounds in essential oils with potential anticancer effects.
Classes Compounds Plant Target cancers Cancer effects Type of Reference
assay

Monoterpene Myrcene PC Human lung adenocarcinoma Increased apoptosis via caspase induction MTT (Bai & Tang,
hydrocarbons (A549) (IC50 0.5 μg/ml) 2020)
Cyclic Limonene Navel orange Lung adenocarcinoma (A549) Reduced cell proliferation (IC50 22.10 µg/ MTT (Yang et al.,
monoterpene (Essential oil) ml) 2017)
Bicyclic α-Pinene PC Human liver cancer (HepG2) Reduced cell growth (IR 39.3%) MTT (Xu et al., 2018)
monoterpene
Acyclic Linalool PC Human ovarian cancer Increased apoptotis and cytotoxicity MTT (Han, Cho et al.,
monoterpene (SKOV3ip1, A2780, HeyA8) 2016)
Oxygenated α-Thujone Thuja Human glioblastoma multiforme Induction of cell death, reduced TB (Pudełek et al.,
monoterpene occidentalis L. (T98G), and human glioblastoma proliferation and invasive exclusion 2019)
(U-87 MG)
Terpineols α-Terpineol Navel orange Lung adenocarcinoma (A549) Increased caspase-dependent cell death MTT (Yang et al.,
Monoterpene (Essential oil) and reduced proliferation (IC50 51.37 µg/ 2017)
ml for 24 h)
Oxygenated 1,8-cineole PC Head and neck squamous cell Reduced proliferation, Wnt/β-catenin MTT (Roettger et al.,
monoterpene carcinoma (HNSCC) activity 2017)
Cyclic α-Phellandrene PC Melanoma(B-16/F-10), and Antinociceptive and tumor-reducing MTT (Pinheiro-Neto
monoterpene Murine (S-180) effect (CI50 436.0 and 217.9 μg/ml) et al., 2021)
Bicyclic 3-carene Gannan Navel Human lung cancer (A549) Reduced proliferation (IC50 70.80 µg/ml) MTT (Yang et al.,
Monoterpene (Essential oil) 2017)
Hydroxylated Perillyl alcohol PC Hepatoma cell Suppress cell invasion and migration Transwell (Ma et al., 2016)
monoterpene
Terpenophenol Bakuchiol PC Human gastric cancer (NUGC3) Increased cell death and reduced cancer MTT (Lv & Liu, 2017)
cell viability (IC50 120 µg/ml for 24 h)
Monoterpenoid Carvacrol PC Human Caucasian gastric Increased cell apoptosis, inhibited CellTiter- (Günes-Bayir
phenol adenocarcinoma (AGS) proliferation, GSH-reducing effects on Glo et al., 2017)
cell (IC50 82.57 μmol/l)
Citral isomers Geranial, Neral, PC Colorectal cancer (HCT116 and Increased mitochondrial-mediated MTT (Sheikh et al.,
and Citral HT29) apoptosis, inhibited cell growth (IC50 2017)
52.63 μM, and 91.5 μM for 72 h)
Tropolone Hinokitiol Purity ≥ 90% Human adenocarcinoma (A549) Reduced cell migration and MTT (Jayakumar
monoterpene chemoprevention et al., 2018)
Bicyclic Myrtenal PC Melanoma (B16F0, B16F10 and Decreased tumor cells migration and MTT (Martins et al.,
Monoterpene SkMel-5) invasion 2019)
Oxygenated Carvone PC Breast ductal carcinoma (MCF-7) Protective effect against tumor (IC50 MTT (Abbas, Kandil,
monoterpen 14.22 μM) & Abbas, 2020)

Note: PC = Pure Compound.

parts of the body and interfere with the normal function of homeostasis α-Thujone is another compound that has anticancer activity. In a
of its host cells (Sung et al., 2021). Today worldwide, it is one of the study carried out by Pudełek et al. (2019), the effect of α-thujone on the
leading causes of morbidity and mortality in the contemporary world, malignancy of glioblastoma multiforme (GBM) cells was investigated.
number second after cardiovascular disease and being one in six human They found that α-thujone exerts the attenuating effect on the prolifer­
deaths and constitutes 30% of all premature deaths occurring in adults ation and viability of GBM cells. They also indicated that α-thujone
(30–69 years). In addition, the number of cancer deaths is predicted to exhibits anti-invasive and pro-apoptotic effects on GBM cells (Pudełek
continue to grow and multiply. This cancer is caused by the influence of et al., 2019).
internal factors, inability, and external factors in lifestyle patterns car­ Furthermore, it has been reported by Potočnjak et al. (2018) that
ried out every day. A food diet can protect from risk factors for carci­ carvacrol exhibits anticancer activity against HeLa cells, a human cer­
nogenesis in the human body (El-Sherif, El-Sherif, Taylor, & Ayakannu, vical cancer cell line. Carvacrol induced cytotoxicity on HeLa cells and
2021). enhanced cisplatin (CP)-induced expression of light chain 3 beta in a
Terpenes and terpenoids are the largest class of organic compounds manner dependent on the inhibition of mitogen-activated protein kinase
produced in the EOs of various plants and have a significant role in the (MEK). This compound, interestingly, also increased HeLa cells resis­
prevention of malignancies in cancer (Silva, Nascimento, Silva, Silva, & tance on CP by suppressing apoptosis in an extracellular signal-regulated
Aguiar, 2021). The anticancer potencies of terpenes and terpenoids have kinase (ERK1)/ERK2-independent manner and promoting the modula­
been reported extensively in recent years (Table 1). Sheikh, Sarker, tion of autophagy in an ERK1/ERK2-dependent manner (Potočnjak
Kamarudin, and Mohan (2017) studied the effect of citral on the pro­ et al., 2018). In addition, carvacrol is a potential source of anticancer
liferation of human colorectal cancer HCT116 and HT29 cells. They agent against the human gastric adenocarcinoma (AGS) cells. Carvacrol
found that citral decreased the expression of Bc-2 and Bcl-xL while inhibited AGS cell proliferation and demonstrated genotoxic, ROS
inducing p53 protein phosphorylation and Bax expression. Citral also generating, and glutathione-reducing effects (Günes-Bayir et al., 2017).
elevated mitochondrial-mediated apoptosis via augmentation of intra­ Han et al. (2016) studied the ability of linalool-incorporated nano­
cellular ROS and attenuated the total GSH levels (Sheikh et al., 2017). particles (LIN-NPs) as novel anticancer agents. They reported that LIN-
Similarly, Jayakumar et al. (2018) evaluated the effect of hinokitiol NP had significant apoptotic and cytotoxicity activity against epithe­
on the migration of A549 lung cancer cells. They observed that hino­ lial ovarian cancer cells (Han, Cho et al., 2016). Moreover, linalool has
kitiol inhibited the migration of A549 cells via several mechanisms, also been reported to exert anticancer activity against hepatocellular
including suppression of MMPs, induction of antioxidant enzymes carcinoma HepG2 cells through modulation of Ras/MAPK and Akt/
(catalase and superoxide dismutase), and activation of caspases-9 and mTOR pathways (Rodenak-Kladniew et al., 2018).
-3. It also significantly induced the cytochrome c expression (Jayakumar In a study by Ma et al. (2016), the anticancer activity of perillyl
et al., 2018). alcohol was demonstrated. They found that perillyl alcohol has an

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A. Masyita et al. Food Chemistry: X 13 (2022) 100217

Table 2
Examples of terpene compounds in essential oils with the potential antimicrobial effects.
Classes Compounds Plant Microorganism strain Antimicrobial effects Type of assay Reference

Monoterpene Myrcene PC Enterococcus faecalis (ATCC 29212), Bacterial growth (MIC > 8 × Agar dilution (Chaves-Quirós
hydrocarbons Streptococcus mutans (ATCC 25175), 102 CFU/ml) et al., 2020)
S. mutans (ATCC 35668), S. mutans (ATCC
UA159), and Lactobacillus rhamnosus
(ATCC 53103)
Terpineols α-Terpineol PC Escherichia coli (CICC 21530), Shigella Good inhibitory effects Two-fold (Huang et al.,
Monoterpene flexneri (CICC 21534), and Salmonella against several gram-negative dilutions 2021)
enterica (CICC 21513) bacteria (MIC 1.531, 0.766,
and 1.531 mg/ml)
Tropolone Hinokitiol PC Bacillus subtilis, S. aureus, E. coli, and (MIC 80, 160, 80, and 320 Agar dilution (Suzuki et al.,
monoterpene Pseudomonas aeruginosa mg/ml) 2019)
Bicyclic Borneol Purity ≥ 98% E. coli (ATCC 43894), Listeria Bacteriostatic activity (MIC Double (Wang et al., 2021)
monoterpene monocytogenes (ATCC 19118), S. aureus 1.25, 5, 5, 10 mg/ml) microdilution
(ATCC 23235), P. aeruginosa (ATCC
27853)
Terpenophenol Bakuchiol PC S. aureus (ATCC29213), MRSA N315, Antibacterial activity (MIC Broth dilution (Li et al., 2021)
MRSA NCTC10442, E. coli (ATCC25922), 6.25, 3.125, 3.125, > 100, method
P. aeruginosa (ATCC9027), Acinetobacter >50, >50, >50, 12.5, and >
baumannii (ATCC17978), A. baumannii 50 μl/ ml)
(R2889), Klebsiella pneumoniae
(ATCC10031), K. pneumoniae
(ATCC14581)
Cyclic D-Limonene PC E. coli (ATCC 8739), S. aureus (ATCC Exhibit strong synergistic Serial Dilution (Zahi et al., 2017)
monoterpene 6538), B. subtilis (ATCC 6633), (MIC 1, 1, 1, and 0.5 µg/ml)
Saccharomyces cerevisiae (ATCC 9763)
Acyclic Geraniol PC B. cereus (MTCC 430), E. coli(MTCC 443) Antimicrobial effect (MIC BHI broth (Syed & Sarkar,
monoterpene 1200 µl/ml all tested) 2018)
Alcohol
Oxygenated 1,8-cineole Purity 99% S. aureus (ATCC 25923), MRSA clinical Effect against microorganisms Serial double (Şimşek & Duman,
monoterpene isolate, P. aeruginosa (ATCC 27853), E. coli (MIC 128, 128, 256, 32, 64, dilutions 2017)
(ATCC 25922), K. pneumoniae (ATCC 128, and 32 g/l)
700603), Enterococcus faecalis (ATCC
51299) Candida albicans (ATCC 90028)
Cyclic α-Phellandrene Purity > 99% Penicillium cyclopium Inhibit the mycelia growth Agar dilution (Zhang, Sun, Chen,
monoterpene (MIC 1.7 ml/L) Zeng, & Wang,
2017)
Bicyclic (+)-3-carene Purity ≥ 90.0% Brochothrix thermosphacta (ACCC 03,870), Had strong antibacterial Agar dilution (Shu et al., 2020)
Monoterpene and Pseudomonas fluorescens (ATCC activity (MIC 20 ml/L)
13,525)
Alkylbenzene p-Cymene Salvia E. coli (ATCC 8739), S. aureus (ATCC Antibacterial activity (MIC Broth (Cutillas, Carrasco,
Monoterpene officinalis 6538), C. albicans (ATCC 10231) 7.5, >15, and 3.75 μl/ml) microdilution Martinez-
(Essential oil) Gutierrez, Tomas,
& Tudela, 2017)
Oxygenated Bornyl acetate S. officinalis E. coli (ATCC 8739), S. aureus (ATCC Antibacterial activity (MIC > Broth (Cutillas et al.,
monoterpene (Essential oil) 6538), C. albicans(ATCC 10231) 15, 15, and > 15 μl/ml) microdilution 2017)
Monoterpenoid Carvacrol PC B. cereus (MTCC 430), E. coli (MTCC 443) Antimicrobial effect (MIC 400 BHI broth (Syed & Sarkar,
phenol µl/ml all tested) 2018)
Acyclic Linalool PC P. aeruginosa (ATCC9027) Antibacterial activity (MIC Medium (Liu et al., 2020)
monoterpene 431 µg/ml) dilution
Alcohol
Citral isomer Citral PC C. albicans (SC5314), C. tropicalis Antimicrobial action (MIC Serial (Gao et al., 2020)
(ATCC1369), S. aureus (ATCC25923) 0.0313, 0.0156, and 0.0313 v/ microdilutions
v%)

Note: PC = Pure Compound.

inhibitory effect on protein synthesis of hypoxia-inducible factor 1α bakuchiol yield its anticancer activity via the induction of
(HIF-1α) which causes a decrease in HCT116 cell growth in a xenograft mitochondrial-dependent cell death and modulation of the phosphoi­
colon tumor model. In addition, perillyl alcohol was also able to increase nositide 3-kinase (PI3K)/protein kinase B (Akt) and mitogen-activated
the expression of p53 and p21, decrease the expression of cyclin D1, c- protein kinase (MAPK) pathways of Nagoya University-Gastric Cancer-
Myc, and S-phase kinase-associated protein 2 (Skp2) and induce cell 3 (NUGC3) cells (Lv & Liu, 2017).
cycle catch in phase G1 in cancer cells (Ma et al., 2016).
The monoterpene myrtenal has also been reported to exhibit anti­
Antimicrobial
cancer properties. Myrtenal plays an important role in controlling tumor
malignancy and metastasis through inhibition of V-ATPase enzymes,
The antimicrobial activity of EOs has been reported in many studies,
disruption of H + flow to V-ATPase-dependent extracellular matrix,
but most of these studies attribute such action to the most common
induction of autophagy, and alteration of ion gradients (Martins,
compounds without analyzing it independently (Guimarães et al.,
Arruda, Costa, Jerdy, De Souza, Santos, De Freitas, Kanashiro, De Car­
2019). Infections caused by sensitive and drug-resistant bacteria or
valho, Sant’anna, Antunes, Martinez-Zaguilan, Souad, Okorokova-
other microorganisms seriously harm human health and global public
Façanha, & Façanha, 2019). Lastly, bakuchiol, an example of mer­
health. Therefore, finding and developing new antimicrobial agents to
oterpene, has been reported to exert anticancer activity in the human
combat multidrug-resistant organisms is essential (Liu et al., 2020).
stomach cancer cells. Preliminary investigation demonstrated that
The use of terpene and terpenoid compounds as antimicrobial agents

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Table 3
Examples of terpene compounds in EO with the potential anti-inflammatory effects.
Classes Compounds Plant Type of inflammation Anti-inflammatory effects Assay/method Reference

Monoterpene Myrcene PC Renal tissues of rats Inhibited the activities of inflammatory ELISA (Yang & Liao, 2021)
hydrocarbons cytokine, pro-inflammatory signalling
Cyclic R- Purity > 99% Gastric ulcer in rats Decreased the levels of TNF-a, IL-6, and ELISA kits (De Souza et al.,
monoterpene (+)-limonene (Sigma Aldrich, IL-1β and increased the level of IL-10 2019)
St. Louis, MO,
USA)
Bicyclic Borneol PC Acute pancreatitis mice Inhibited TNF-α, IL-1β, IL-6, and ELISA (Bansod et al., 2021)
monoterpene model modulated Nrf2/NF-κB pathway
Tropolone Hinokitiol PC Inflammation in primary Inhibited LPS-mediated up-regulation Quantitative Real- (Lee et al., 2017)
monoterpene human keratinocytes of pro-inflammatory factors including Time PCR
tumor necrosis factor alpha, IL-6, and
prostaglandin E2 (PGE2), and Sirt1
activity
Terpenophenol Bakuchiol Psoralea Cerebral ischemic injury in Exhibit its anti-inflammatory property Immuno- (Xu, Gao, Wang,
corylifolia mouse BV-2 microglia via activating Nrf2 signaling fluorescence Yang, & Xie, 2021)
(Seeds essential staining
oil)
Bicyclic α-Pinene PC Focal cerebral Neuroprotective effect during ischemic ELISA (Khoshnazar,
monoterpene ischemia–reperfusion in stroke through attenuating Parvardeh, & Bigdeli,
rats neuroinflammation. 2020)
Acyclic Linalool Boswellia Ear edema model and a More potent pharmacological effects on Immuno- (Li, Yang, Li, Zhang,
monoterpene carterii formalin-inflamed hind hind paw inflammation and COX-2 histochemistry & Tang, 2016)
Alcohol paw model overexpression
Acyclic Geraniol PC Lungs in mice model Improved the inflammatory changes ELISA (Lin et al., 2021)
monoterpene
Alcohol
Cyclic α-Phellandrene PC Wound healing Suppressed the overproduction of pro- ELISA (De Christo Scherer
monoterpene inflammatory cytokines of IL-6 and et al., 2019)
TNF-α.
Hydroxylated Perillyl alcohol Purity 96% Lung tissue in rats Inhibited cellular inflammation ELISA (Beik et al., 2021)
monoterpene
Citral isomer Citral Purity ≥ 95% Hyperalgesia and pleurisy Anti-inflammatory activities ELISA (Campos, Lima,
in mice Trindade, Souza,
Mota, Heimfarth, &
Thangaraj, 2019)
Monoterpenoid Carvacrol PC Asthma in rats Reduced of AEC, IgE, IL-4, IL-5, IL-13, Colorimetric and (Ezz-Eldin, Aboseif,
phenol TNF-α, IFN-γ, iNOS and MDA Quantitative Real- & Khalaf, 2020)
Time PCR
Oxygenated 1,8-cineole PC Upper Ileum Tissues Prevented low-grade inflammation Quantitative Real- (Jiang et al., 2021)
monoterpene Time PCR

Note: PC = Pure Compound.

is very promising. It has been used in several industrial fields, including suitable for use as promising food additives (Wang et al., 2021).
cosmetics, foods, and some health care products, such as hair tonics, Hinokitiol is effective against Candida strain panels with several
toothpaste, eyelid cleansers, hair restorers, skin soaps, and body lotions azole-resistant mechanisms and inhibits the growth of Candida albicans
(El Hachlafi et al., 2021). Terpene and terpenoid compounds have been (Jin et al., 2021). The mechanism of action of hinokitiol is attributed to
reported to yield bactericidal effects (Guimarães et al., 2019). For the chelated effect of intracellular iron fungus and inhibits the respira­
example, limonene have synergistic modulation effects with gentamicin tion of fungal cells but has little effect on the mammalian cells. It has
antibiotics in the inhibition of Gram-positive Staphylococcus aureus and been reported that hinokitiol also inhibits the activity of mitochondrial
Gram-negative Escherichia coli as and several resistant bacteria (Costa respiratory chains complex I and II and reduces the potential of mito­
et al., 2019). In addition, a combination of limonene and ε-Polylysine chondrial membranes, thereby reducing intracellular ATP synthesis and
demonstrates an additive and useful synergistic effect against E. coli, increasing the intracellular reproductive stress. Thus, hinokitiol shows
S. aureus, Bacillus subtilis and Saccharomyces cerevisiae (Zahi, El Hattab, low potential to induce resistance in some Candida species and greatly
Liang, & Yuan, 2017), improves the survival of Candida-infected Galleria mellonella (Jin et al.,
Monoterpene terpineol’s isomers (α-terpineol, terpinen-4-ol, and 2021). Furthermore, hinokitiol has also been demonstrated to yield
δ-terpineol) have a good inhibitory effect on several Gram-negative prospective antibacterial effect with low or no negative effect on the
bacteria, especially Shigella flexneri with bacterial membrane perme­ human host or environment (Suzuki et al., 2019).
ability mechanisms resulting in the release of nucleic acids and proteins Other examples of EO with antimicrobial effect are eugenol (Devi,
along with a decrease in membrane potential. In addition to that, the Nisha, Sakthivel, & Pandian, 2010). Eugenol showed rapid bactericidal
release of AKP indicates that the bacterial cell wall is destroyed, thus the action against Salmonella enterica serovar Typhimurium. Eugenol also
potential use of terpineol in food as a natural antibacterial agent that is demonstrated excellent bactericidal activity against strains of S. aureus.
capable to destroy cell membranes and walls, resulting in bacterial cell The compounds carveol, citronellol, and geraniol have a rapid bacteri­
death (Huang et al., 2021). Borneol and citral also have synergistic ef­ cidal effect against E. coli. Furthermore, carvacrol, l-carveol, eugenol,
fects as bacteriostatic and antibiofilm agents in the packaging materials trans-geraniol, and thymol, showed higher activity when compared to
and common surface disinfectants. The synergistic effects of borneol and sulfanilamide. The inhibition of microbial growth and the death of
citral demonstrates a good elimination effect on the formation of bio­ bacterial cells is based on the loss of integrity in the function of cellular
films produced by Listeria monocytogenes and Pseudomonas aeruginosa, membranes (Guimarães et al., 2019). Terpenes and other terpenoid
most likely attributed to the ability of those two components to increase compounds, such as bakuchiol, α-pinene, linalool, champene, geraniol,
porosity and lytic effect on bacterial cell membranes as particularly 1,8-cineole, α-phellandrene, 3-carene, p-cymene, perillyl alcohol, bornyl

7
A. Masyita et al. Food Chemistry: X 13 (2022) 100217

acetate, and citral isomers, also have been reported to yield inhibitory cytokines and has the potential to alleviate cerulein-induced acute
effects on the growth of microorganisms (Table 2). These convincing pancreatitis by reducing oxidative damage and inflammation of the
data further indicate the potential use of these compounds as efficient pancreas in a manner dependent on the modulating of the Nrf2/NF-κB
antimicrobial agents in the food industry (Zahi et al., 2017), thus has a pathway (Bansod et al., 2021).
valuable contribution in supporting human health. Another example is bakuchiol, a meroterpene in the class of terpe­
nophenol, and hinokitiol, a natural monoterpenoid. Bakuchiol has been
Anti-inflammatory demonstrated to be effective in the suppression of pro-inflammatory
cytokine expression and mitigation of delayed hypersensitivity re­
Recent decades have shown that terpenes and terpenoids are physi­ sponses compared to the control group (Kumar et al., 2021). Hinokitiol
ologically important to alleviate various symptoms caused by inflam­ inhibits LPS-mediated regulation, including tumor necrosis factor-alpha,
mation, most likely by inhibiting multiple pathological steps in the IL-6, and prostaglandin E2 (PGE2). Hinokitiol is suggested to act
inflammatory process (Kim, Song, Cho, & Lee, 2020). Inflammation is a through the inhibition of LPS-mediated proinflammatory signals via the
protective response of the host to non-self objects that are usually activation of histone sirt1 deacetylase in primary human keratinocytes.
generated by microbial infection and/or tissue damage. Dysregulation of Hence, hinokitiol has been suggested as a potential therapeutic agent in
inflammatory responses can lead to acute and chronic inflammatory the treatment of inflammatory skin diseases such as psoriasis (Lee,
diseases that cause excessive or long-lasting tissue damage (Chen et al., Moon, Lee, & Park, 2017).
2017).
Macrophages, one of key immune cells, play a central role in many
different immune pathological phenomena during inflammation, Antioxidant
including overproduction of pro-inflammatory cytokines and inflam­
matory mediators, such as interleukin-1β (IL-1β), IL-6, tumor necrosis Some EOs have an important role in reducing oxidative stress and
factor-alpha (TNF-α), and nitric oxide (NO) synthesized by non-reduced often used to prevent several chronic diseases. Chamazulene, a bicyclic
NO synthase (iNOS), and prostaglandin E2 (PGE-2) synthesized by sesquiterpene derivative from EOs of Matricaria chamomilla, was able to
cyclooxygenase-2 (COX-2). Lastly, a central transcription factor, nu­ balance ROS level on bovine aortic endothelial cells-1 (BAECs), which
clear-κB (NF-κB) factor, holds a central role in the expression of pro- increase due to high glucose and H2O2 treatment (Querio et al., 2018).
inflammatory genes during inflammation (Liu, Zhang, Joo, & Sun, Ursolic acid which isolated from Entada abyssinica is a pentacyclic tri­
2017). terpenoid carboxylic acid. Ursolic acid has antioxidant activity with IC50
Some cellular processes, including oxidative stress and autophagy, 1.43 ± 0.080, 2.87 ± 1.19, and 7.04 ± 1.29 µg/ml by using FRAP, DPPH,
also play an essential role in inflammation. Reactive oxygen species and ABTS method, respectively (Dzoyem et al., 2017). FRAP, DPPH, and
(ROS), which results from several sources, including mitochondria, ABTS are radical compound which can assist in the measurement of
mediate increased leukocyte migration and junctional permeability antioxidant activity through color change. DPPH will change into a non-
through various signaling mechanisms. In addition, a recent study radical compound (diphenylpicrylhydrazine), characterized by a change
showed that ROS regulates the release of IL-1β by directly interfering in the color of the solution from purple to pale yellow, if its free electrons
with NF-κB signals (Warnatsch et al., 2017). bind to the hydrogen atom of an antioxidant compound. In the ABTS
The application of terpenes and terpenoids to alleviate inflammation method, the solution will change from blue or green to colorless due to
has been shown successful in the mitigation of respiratory inflammation, the acceptance of proton donors from antioxidant compounds. Mean­
atopic dermatitis, arthritis, and neuroinflammation (Kim, Song et al., while, in the FRAP method, the solution will change color from yellow to
2020). Table 3 shows that terpene compounds and terpenoids are blue when ferri-tripyridyl-triazine (Fe(III)TPTZ) becomes ferro-
beneficial as an anti-inflammatory in some disease conditions. tripyridyl-triazine (Fe(II)TPTZ) due to electron transfer from antioxi­
The prospective anti-inflammatory effect of myrcene in the treat­ dant compounds (Moon & Shibamoto, 2009).
ment of renal inflammation was tested in the adrenalectomized rat Some terpeneoids (α-pinene, limonene, nerol, terpinol, geraniol,
models (Islam et al., 2020). The mechanisms were suggested to be linalool, and myrcene) are responsible for specific aroma in wine.
associated with the downregulation of pro-inflammatory cytokine (IL- α-Pinene showed the strongest radical scavenging effect with IC50 12.57
1β, IL-6, and TNF-α) and anti-inflammatory markers (IL-4 and IL-10) as ± 0.18 mg/ml, followed by limonene and nerol with IC50 13.35 ± 0.26
well as the upregulation of endogenous antioxidants such as catalase and 26.08 ± 2.28 mg/ml, respectively. This is in line with the result of
(CAT), superoxide dismutases (SODs) and glutathione (GSH) (Islam reducing power assay, where α-pinene has the greatest reducing power
et al., 2020). among others (213.7 ± 5.27 mg/ml), followed by limonene (133.48 ±
Limonene, a cyclic monoterpene, has been reported to exert gastro­ 6.22 mg/ml), nerol (79.15 ± 3.75 mg/ml), terpinol (73.92 ± 3.34 mg/
protective effect in rats (De Souza et al., 2019). The precise mechanism ml), geraniol (73.78 ± 3.94 mg/ml), linalool (43.97 ± 1.09), and the
of its gastroprotective action remains unclear. However, current exper­ lowest was myrcene (21.59 ± 1.14 mg/ml) (Wang et al., 2019).
imental evidence suggested that this effect may be due to its ability in Magnolia biondii, one of traditional Chinese herb, contain many
the modulation of the oxidative stress (via upregulation of endogenous active components in its essential oil. Of all, α-terpineol showed the
antioxidant glutathione peroxidase) and the alleviation of inflammatory highest % rate of scavenging (84.1%) followed by c-cadinene (83.9%),
responses (via inhibition of NF-κB-mediated gene expression) (De Souza geraniol (75.5%), linalool (65.5%), and citronellol (58.1%) by DPPH
et al., 2019). assays. Similar results were also obtained in the ABTS assays, where
Several terpenes and terpenoids such as (+)-α-terpineol, these five components had the highest scavenging activity compared to
(− )-β-pinene, and (+)-α-pinene reported to reduce the expression of the others, ranging from 89.1% to 83.0% (Nie et al., 2020). Essential oil
genes associated with inflammation (IL-4 and IL-13) and secretion of of Cinnamon contains cinnamaldehyde which has high scavenging rate
β-hexosaminidase in RBL-2H3 cells stimulated by LPS. The application of 93.0% by using DPPH assay (Farag, Alagawany, & Tufarelli, 2017).
of these compounds in the treatment of inflammatory conditions and the Eugenol and isoeugenol which found in a variety of plants including
basis for the development of new anti-inflammatory drugs (Yang, Choi, cinnamon, basil, clove, spices, and nutmeg have quite promising anti­
Kim, Eom, & Park, 2021). Borneol, for example, has been reported to oxidant activity, with EC50 of 22.1 ± 3.5 and 17.6 ± 4.1 µg/ml for DPPH
significantly increase the activation of nuclear factors E2-related factor 2 assay, 146.5 ± 5.6 and 87.9 ± 4.7 µg/ml for ABTS assay, and 11.2 ± 1.5
(Nrf2) and the expression of superoxide dismutase (SOD) 1 but at the and 18.4 ± 1.2 µg/ml for FRAP assay, respectively. These results indi­
same time downregulate the expression of NF-κB and p65. Treatment cate that isoeugenol has slightly higher scavenging activity than eugenol
with borneol significantly inhibited the pro-inflammatory expression of (Zhang, Zhang, Xu, & Hu, 2017).

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A. Masyita et al. Food Chemistry: X 13 (2022) 100217

Anti-allergic used in vitro digestion method (Jones, Caballero, & Davidov-Pardo,

2019). In vitro methods can also be carried out using a Caco-2 cell
Allergic diseases are characterized by inflammation with infiltration model wherein the absorbed target compound is collected on the
of T cells and granulocytes (eosinophils, neutrophils, and mast cells). basolateral side of the monolayer model cell (Jones et al., 2019). In vivo
Mast cells play a major role in almost all allergic diseases, generally in methods were carried out using animal models prior to clinical studies.
the end reaction of allergic disease (Modena, Dazy, & White, 2016). The matrix of medicinal plants is related to the bioavailability of the
Mast cells begin to synthesize prostanoids and proinflammatory leuko­ terpenes they contain because they must pass through digestion in the
trienes, and subsequently produce inflammatory cytokines, such as IL-4, mouth and stomach before accessing the small intestine. Furthermore,
IL-5, IL-13, IL-1α/β, thereby stimulating the activation of other cells these compounds will undergo mechanical and enzymatic actions,
such as neutrophils, monocytes, basophils, eosinophils and lympho­ changes in pH conditions, as well as water-soluble transformations,
cytes. Anti-allergic compounds derived from plants, animals, and mi­ which occur mainly in the liver and other tissues such as the lungs,
crobes, with various mechanisms of action such as binding to the epitope gastrointestinal, kidney, blood and brain. Terpenes describe high lipo­
present in allergens, affecting gut microbiota and intestinal epithelial philic behavior that influences their solubility in the aqueous phase of
cells, changing antigen presentation and T cell differentiation, and the gut lumen, thus incorporation with the lipid phase becomes very
inhibiting effector cell degranulation (Yang, Li, Xue, Huang, & Wang, important in the bioavailability of terpenes, either during digestion or
2021). during food processing (Mouhid et al., 2017). Even though intravenous
Some terpenes and terpenoids have been studied for anti-allergic administration is assumed has maximal (100%) bioavailability of EOs,
activity. Atractylone (Atr), one of sesquiterpene components from skin application, oral intake, and inhalation are the primary intake
Atractylodes japonica, can inhibit rat peritoneal mast cells (RPMC) routes of EOs (Stevanovic et al., 2020). Some studies have been con­
degranulation, tryptase and histamine release, and intracellular calcium ducted in order to understand bioavailability and bioaccessibilty of
levels. Also, reduced tryptase and histamine release from PMA plus terpenes and terpenoids (Table S1).
A23187-stimulated HMC-1 cells, led to decreased actvity and expression Terpenoids easily enter the body by penetration through the skin due
of histidine decarboxylase in activated HMC-1 cells. Atr decreased levels to their lipophilic properties although the amount depends on the area of
of histamine, IgE, IL-4, IL-5, IL-6, vascular endothelial growth factor, skin applied, skin characteristics, concentration of compounds and
and IL-13 in the serum of PCA-induced mice. Atr has activity as a exposure time. Following oral administration of terpenoids, the upper
treatment for allergic reactions mediated by mast cells (Han, Moon gastrointestinal tract did not have a significant role in the absorption.
et al., 2016). Carvone (S- and R-) at concentrations 10 mg/kg via oral However, using the route of inhalation, terpenoids may be absorbed by
route has been reported to reduce the total eosinophil and leukocytes the lungs so that they are available systemically. This absorption de­
counts in the murine model of airway allergic inflammation induced by pends on the type of compound and the respiratory mechanics of the
sensitization and challenge with ovalbumin (OVA). S-carvone signifi­ subject. Enterohepatic circulation, pulmonary and renal excretion play a
cantly increased the concentrations of IFN- and neutrophil counts in the role in the elimination of terpenoids in the form of feces, expired air, and
BAL of allergic mice. R-carvone could stimulate IL-10 synthesis and urine. A minor part is eliminated along with the feces, and the rest
inhibit IgE secretion (Ribeiro-Filho et al., 2020). β-Amyrin, 2α,3α,23- through the urine as terpene conjugates and in the expired air with CO2.
trihydroxyursa-12,20(30)-dien-28-oic acid, and euscaphic acid at 10 Drug biotransformation occurs in the liver by phase I and phase II re­
µM, inhibited histamine release with percentage of inhibitions of 46.7, actions, but in many terpenoids it takes only one phase to eliminate
57.9, and 54.2%, respectively. In addition, β-amyrin and 2α,3α,23- these volatile compounds (Jäger & Höferl, 2020; Kohlert et al., 2000).
trihydroxyursa-12,20(30)-dien-28-oic acid showed strong inhibition of Camphor undergoes phase II metabolism to 5-exo-hydroxycamphor.
TNF- α and IL-6 in the test for pro-inflammatory cytokines (Choi, Kim, Menthol and peppermint oil are excreted through the kidneys as
Kim, & Kim, 2016). menthol glucuronide. Terpenoids have high clearance and a short
Citronellol, one of major component from geranium EOs, at con­ elimination half-life making accumulation of their metabolites are
centrations 0.5 mM can inhibit degranulation of mast cells by 69.4% and impossible.
significantly inhibit IgE- induced tumor necrosis factor -α (TNF-α) pro­ Some EOs were used as penetration enhancer of drug via transdermal
duction (Kobayashi et al., 2016). Vernodalin isolated from Vernonia administration. Galangal EO was added to flurbiprofen microemulsion
amygdalina increase filaggrin (FLG) mRNA expression levels and reduce gel to increase bioavailability of flurbiprofen as anti-inflammatory drugs
IL-33mRNA expression in mice (vs. control group) also significantly (Dong et al., 2020). Menthol and menthone can enhance penetration of
reduce the dermatitis score (vs. control) in regard to ear skin lesions at ligustrazine hydrochloride, an anti-platelet aggregation, on transdermal
100 µg/ml via topical administration (Hirota & Ngatu, 2018). Moja­ absorption (Wang et al., 2017). In the oral administration, the main
banchromanol, a constituent isolated from Sargassum horneri, has anti- absorption site, the intestine, the absorption rate of EOs depends on
allergy effect on bone marrow-derived cultured mast cells. Mojabanch­ lipophilicity, polarity, solubility, and molecular weight (Stevanovic
romanol shows inhibitory effect on the β-hexosaminidase release and et al., 2020). Due to different physiological and chemical condition of
inhibited the mRNA expression levels of allergic cytokines in bone absorption site in GI tract, different rates of absorption can be happened
marrow cultured mast cells (BMCMCs) (Kim, Han et al., 2020). in different terpenes. For example, sesquiterpene lactones and diterpene
lactones, which have similar structures, have often been reported to
Bioaccessibility and bioavailability of terpenes and terpenoids have changeable pharmacokinetics, particularly unstable absorption
and extensive metabolism. Although this compound is quite permeable
Bioavailability is a term that refers to a measure of the rate and in the intestinal epithelium, its absorption can be unstable due to the
fraction of the initial dose of a drug that successfully reaches the site of influence of gastrointestinal pH and efflux transporters (P-glycoprotein).
action or body fluids of the target drug to produce the desired biologic P-gp expression increases from the proximal to the distal end of the small
effect (Currie, 2018). Bioavailability includes two interrelated parts, intestine causing a different absorption area of the P-gp substrate.
namely: bioaccessibility and bioactivity. Bioaccessibility is defined as Sesquiterpene lactone and diterpene lactone tend to be absorbed most
the quantity or fraction released from the food matrix in the digestive effectively in the duodenum, followed by the jejunum, ileum and colon
tract that is available for absorption (Thakur et al., 2020). (Liu et al., 2019). In addition, differences in pH in the GI tract also affect
Studies on the bioavailability and bioaccessibility of a compound are terpene absorption, where the pH of the stomach, duodenum and colon
generally carried out by in vitro or in vivo methods. Simulation of the is 1.2, 5.5 and 7.0, respectively (Wang et al., 2020).
condition of the gastrointestinal system by adjusting the pH, digestive
enzymes and some chemical reactions that occur, is the most widely

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Table 4
Examples of conducted studies on preservation of food products by essential oils.
Food product Investigated essential oil Main bioactive compounds Key findings Reference

Bread Cymbopogon citratus (z)-Citral (62.58%), cis-verbenol (6.29%), The vapor of lemongrass EO (750 µl of EO/ (Mani López, Valle
(lemongrass) geranyl acetate (5.36%), isoeugenol (4.52%), Lair) could inhibit Penicillium expansum Vargas, Palou, & López
caryophyllene (3.91%) inoculated on bread for 21 days at 20 ◦ C. Malo, 2018)
Cake Thymus vulgaris Thymol (53.57%), p-cymene (15.51%), Addition of encapsulated thyme essential oil (Gonçalves et al., 2017)
limonene (7.14%), carvacrol (6.93%), trans- (0.60 mg/ml) in the cake formulation
caryophyllene (3.26%), α-pinene (2.80%) enhanced the shelf life of the product for 30
days of storage.
Dry fruits Mentha cardiaca L. Carvone (59.6%), limonene (23.3%), β-myrcene M. cardiaca EO showed strong antifungal (Dwivedy, Prakash,
(2.5%), 1,8-cineole (2.1%), β-bourbonene activity (MIC 1.25 µl/ml) against Chanotiya, Bisht, &
(1.5%), cis-dihydrocarvone (1.5%) biodeterioration fungi of dry fruits and Dubey, 2017)
potentially to reduce aflatoxin secretion.
Green gram Lippia alba Geranial (36.94%), neral (29.32%), myrcene Utilization of a dose of 80 μl/0.25 L of Lippia (Pandey, Sonker, &
seeds (18.65%), α-caryophyllene (2.07%), eugenol alba oil in green gram seeds significantly Singh, 2016)
(1.82%), α-phelandrine (1.02%) inhibited the proliferation of fungal and
production of aflatoxin B1 without affecting
the seed germination rate during storage.
Orangina Eucalyptus globulus essential oil 1,8-cineole (94.03%), α-pinene (2.93%), EGEO (0.8 to 4 μl/ml) was effective and (Boukhatem et al., 2020)
fruit juice γ-terpinene (1.93%), α-phellandrene (0.59%), potent to reduce S. cerevisiae growth in the
β-pinene (0.20%), myrcene (0.19%) fruit juice of Orangina.
Pineapple Cymbopogon citratus D.C. Stapf. Geraniol (46.16%), neral (31.74%), geranyl- The incorporation of CCEO in pineapple juice (Leite et al., 2016)
juice essential oil (CCEO) acetate (4.34%), caryophyllene (2.02%), 6- at all tested concentrations (5, 2.5, and 1.25
methyl-5-hepten-2-ona (1.77%), dipentyl- μl/ml) caused a decrease in viable counts of
ketone (1.06%), linalool (1.03%) E. coli, L. monocytogenes, and Salmonella
enterica.
Chicken Zingiber officinale(Ginger) α-Zingiberene (24.96%), β-sesquiphellandrene Ginger essential oils nanoemulsion (6%) (Noori, Zeynali, &
breast (12.74%), sesquisabinene hydrate (6.19%), significantly reduced L. monocytogenes growth Almasi, 2018)
fillets camphene (5.90%), zingiberenol (4.26%), (E)- in refrigerated chicken filets during 12 days of
citral (3.93%), sabinene (3.75%), (E)-farnesene storage.
(3.73%), and italicene (3.21%)
Chicken Ziziphora clinopodioides Carvacrol (65.22%), thymol (19.51%), p- Z. clinopodioides EO (0.3%) efficiently (Shahbazi, Karami, &
meatballs cymene (4.86%),and γ-terpinene (4.63%) inhibited the growth of L. monocytogenes in Shavisi, 2018)
chicken meatball during 12 days storage 4 ◦ C
without any unfavorable sensory properties.
Dry Juniperus communis L. β-myrcene (14.12%), sabinene (9.51%), d,l- Juniperus communis EO can be utilized to (Tomović et al., 2020)
Fermented limonene (8.36%), 4-terpineol (6.88%), control foodborne pathogens
Sausages α-amorphene (5.43%), β-pinene (5.39%), (L. monocytogenes, Salmonella spp., E. coli, and
caryophyllene (3.94%), p-cymene (3.92%), sulfite-reducing clostridia) in dry fermented
germacrene D (3.81%), sausages during storage period (225 days).
The sample with 0.10 µl/g of Juniperus
communis EO had untypical flavor.
Ground beef Melaleuca alternifolia (tea tree) Terpinen-4-ol (43.1%), γ-terpinene (22.8%), The incorporation of 1.5% v/w Melaleuca (Silva, Figueiredo,
α-terpinene (9.3%), α-terpineol (5.2%), alternifolia EO in ground beef was effective Stamford, & Silva, 2019)
terpinolene (3.5%), and α-pinene (3.0%) against L. monocytogenes with MIC and MBC
values of 0.10 μl/g and 0.15 μl/ml,
respectively. Melaleuca alternifolia EO was not
significantly effective in the sample with the
suspension at 1.5 × 108 CFU/ml.
Minced beef Citrus limon (lemon) β-Pinene (25.44%), limonene (39.74%), linalool The application of Citrus limon EO (0.06 and (Ben Hsouna, Ben
meat (2.16%), α-terpineol (7.30%), linalyl acetate 0.312 mg/g) can be considered as a natural Halima, Smaoui, &
(3.01%), acetate geranyl (3.03%), nerolidol substance in controlling growth of Hamdi, 2017)
(6.91%), acetate neryl (1.74%), and farnesol L. monocytogenes during storage at 4 ◦ C of
(4.28%). minced beef meat.
Sausages Thyme essential oil Thymol (38.2%), p-cymene (25.4%) and Thyme EO inhibited development of (Blanco-Lizarazo,
terpineol with γ-terpinene (16.2%), α-pinene L. monocytogenes in sausages. The main Betancourt-Cortés,
(2.2%) constituents of thyme EO related to thymol Lombana, Carrillo-
that disrupts membrane cells and reduces the Castro, & Sotelo-Díaz,
activity of ATPase of L. monocytogenes. 2017)
Turkey meat Zataria multiflora Boiss and Zataria multiflora Boiss: carvacrol (51.55%), Nanoemulsion of BEO and ZEO could extend (Keykhosravy, Khanzadi,
Bunium persicum Boiss thymol (25.49%), p-cymene (5.23%), and the shelf life of turkey meat to 9 days. The Hashemi, & Azizzadeh,
γ-terpinene (4.44%). Bunium persicum Boiss: chitosan-loaded nanoemulsion containing 2020)
cumic aldehyde (38.39%), p-cymene (18.36%), ZEO 1% provided the best antimicrobial
and 2-caren-10-al (13.26%) activity. Nanoemulsion containing BEO and
ZEO significantly decreased the population of
Salmonella Enteritidis and L. monocytogenes
about 3 log CFU/g and 2 log CFU/g,
respectively.
UHT milk Syzygium aromaticum(clove), Syzygium aromaticum (clove): eugenol (74.5%), The combination of 2.4% S. aromaticum, (Falleh et al., 2019)
Cinnamomum zeylanicum caryophyllene (20.4%), aceteugenol (2.6%), 38.2% L. stoechas, and 59.4% C. zeylanicum
(cinnamon), Myrtus communis β-selinene (2%). Cinnamomum zeylanicum significantly restricted the viability of E. coli
(myrtle), and Lavandula stoechas (cinnamon): Cinnamaldehyde (89%), camphene to 1 × 106 CFU.ml− 1. These findings are to be
(lavender) (3.5%), α-terpineol (1.6%), 1,8-cineole (1.6%). taken into consideration for a successful
Myrtus communis (myrtle): Butanoic acid, 2- application of these essential oils as food
methyl, 2-methylbutyl ester (74.6%), 1,8- preservatives in milk and dairy industries.
cineole (11.5%), d-limonene (6.5%), linalool
(continued on next page)

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A. Masyita et al. Food Chemistry: X 13 (2022) 100217

Table 4 (continued )
Food product Investigated essential oil Main bioactive compounds Key findings Reference

(1.9%). Lavandula stoechas (lavender): camphor

(35.4%), α-fenchone (32.5%), 1,8-cineole
(7.4%), camphene (4.3%), α-pinene (2.8%).

Potential and limitation application of EO as natural food medical industries with several potential activities such as anticancer,
preservatives antimicrobial, anti-inflammatory, antioxidant, and anti-allergic.
Nevertheless, more studies are necessarily required to understand the
One of the crucial matters in the food industry is to provide safe and mechanism behind the biological properties of EOs. Major bioactive
healthy food. Thereby, to improve safety and extend the shelf life of food compounds of EOs need to be clearly elucidated to improve their po­
products, many synthetic preservatives have been permitted to be used tential efficiencies in disease management. In addition to their function
in the food industry to prevent contamination of foodborne pathogens in health, EOs show high potential to be used as natural food pre­
and/or to control spoilage (Yousefi, Khorshidian, & Hosseini, 2020). servatives in the food industry. However, organoleptic impact and
Nevertheless, following the consumers’ preference to consume food probable contamination of EOs in food products have been suggested to
products with natural substances, the food industry has also been limit their use. Indeed, careful and thorough investigations are urgently
exploiting the use of natural preservatives in their products. In this needed to reduce the disadvantages of EOs to meet the needs for food
sense, EOs exhibit various activities including antibacterial, antioxidant industry applications. Accordingly, scientific efforts need to be further
and antifungal properties that are considered as alternative eco-friendly initiated and developed to evaluate the effects of incorporating EOs into
food preservatives (Pandey et al., 2017). packaging systems and to ensure their safety for the consumers and the
Several EOs and their constituents were approved by the United environment.
States Food and Drug Administration (FDA) as Generally Recognized as
Safe (GRAS) status to be used as flavorings and food preservatives (Ben
Declaration of Competing Interest
Jemaa et al., 2017). The registered EOs have GRAS status including
basil, cinnamon, clove, coriander, ginger, lavandin, menthol, nutmeg,
The authors declare that they have no known competing financial
oregano, rose, sage, and thyme EOs. Likewise, the reported EO constit­
interests or personal relationships that could have appeared to influence
uent comprise carvacrol, carvone, citral, cinnamaldehyde, eugenol,
the work reported in this paper.
limonene, linalool, thymol, and vanillin. The main constituents of EOs
such as terpenes, play an important role in food safety without affecting
the quality (Falleh et al., 2020). Acknowledgements
EOs have the potential to be used as a food preservative for various
food products (Table 4) such as meat, breads, grains, fruits, vegetables, Funding for open access charge: Universidade de Vigo/CISUG.
milk, and dairy products (Pandey et al., 2017). Various pathogens
including E. coli, Clostridium spp., Salmonella spp., Campylobacter jejuni, Appendix A. Supplementary data
Aeromonas hydrophila, S. cerevisiae, Penicillium expansum, and Listeria
monocytogenes involved in the spoilage of food products. Among them, Supplementary data to this article can be found online at https://doi.
L. monocytogenes has been reported as the main causative agent of org/10.1016/j.fochx.2022.100217.
serious diseases in humans and animals (Yousefi et al., 2020).
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