# Antimicrobial Properties of Plant Essential Oils against Human Pathogens and Their Mode of Action: An Updated Review

Authors: Mallappa Kumara Swamy; Mohd Sayeed Akhtar; Uma Rani Sinniah
Journal: Evidence-Based Complementary and Alternative Medicine
 (2016)

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## Abstract

A wide range of medicinal and aromatic plants (MAPs) have been explored for their essential oils in the past few decades. Essential oils are complex volatile compounds, synthesized naturally in different plant parts during the process of secondary metabolism. Essential oils have great potential in the field of biomedicine as they effectively destroy several bacterial, fungal, and viral pathogens. The presence of different types of aldehydes, phenolics, terpenes, and other antimicrobial compounds means that the essential oils are effective against a diverse range of pathogens. The reactivity of essential oil depends upon the nature, composition, and orientation of its functional groups. The aim of this article is to review the antimicrobial potential of essential oils secreted from MAPs and their possible mechanisms of action against human pathogens. This comprehensive review will benefit researchers who wish to explore the potential of essential oils in the development of novel broad-spectrum key molecules against a broad range of drug-resistant pathogenic microbes.


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## Body

## 1. Introduction

Medicinal and aromatic plants (MAPs) constitute a large part of natural flora and are considered an important resource in various fields such as the pharmaceutical, flavor and fragrance, perfumery, and cosmetic industries [1]. At present, more than 80% of the global population depends on traditional plant-based medications for treating various human health problems [2–4]. According to an estimate, the worth of herbal products on the global market is approximately 62 billion USD, and it is predicted to grow up to 5 trillion USD by the year 2050 [5]. More than 9000 native plants have been identified and recorded for their curative properties, and about 1500 species are known for their aroma and flavor. Essential-oil–based products or natural aroma chemicals are in higher demand in the cosmetic, food, perfume, and pharmaceutical industries, and more than 250 types of essential oils, at a value of 1.2 billion USD, are traded annually on the international market [3, 6].Essential oils obtained from MAPs are aromatic in nature because of a mixture of multifarious chemical substances that belong to different chemical families, including terpenes, aldehydes, alcohols, esters, phenolic, ethers, and ketones [3, 7]. Essential oils have tremendous business potential on the global market owing to their unique flavor and fragrance properties and also biological activities [6, 8]. Essential oils are employed in aromatherapy and for the treatment of several diseases including cardiovascular disease, diabetes, Alzheimer’s, cancer [9]. The antimicrobial impacts of essential oils and their chemical components have been recognized by several researchers in the past [3, 10–13]. Furthermore, studies have shown the synergistic effect of any two or more ingredients of essential oils against various human pathogens [14, 15].More recently, the prevalence of antimicrobial drug resistance has prompted researchers to discover novel antimicrobial lead molecules to treat various human pathogens [16]. Some of the presently available synthetic drugs fail to inhibit many pathogenic microbes. In addition, the use of synthetic chemicals for the control of pathogenic microorganisms is limited because of their carcinogenic effects, acute toxicity, and environmental hazard potential. In this regard, the exploitation of essential oils to control epidemic multidrug-resistant pathogenic microorganisms can be useful to combat various infectious diseases [17]. Therefore, the present review details the antibacterial, antifungal, and antiviral potentials of essential oils extracted from MAPs as well as their therapeutic relevance and possible mechanisms involved in the reticence of human pathogenic microorganisms. In addition, this review suggests avenues for more research studies on essential oils to be used against drug-resistant microbial pathogens.


## 2. Chemical Composition of Essential Oils

Essential oils have the ability to hamper the growth of a diverse range of pathogens because of the presence of natural compounds produced by the organs of plants. Importantly, the unique aroma and other bioactive properties of an essential oil depend on its chemical constituents. In MAPs, essential oils generally accumulate in the secretary canals or cavities and glandular trichomes and sometimes in the epidermal cells [4]. Essential oils and their chemical constituents exhibit more bioactivity when present in the oxygenated or active form. In general, the chemical composition of essential oils is relatively complex, and about 20 to 60 different bioactive components are observed in many of these essential oils. Many of these compounds are pharmaceutically appreciated for their numerous culinary properties [1, 4, 7, 13]. Usually, the chemical characterization of many essential oils reveals the presence of only 2-3 major components at a fairly high concentration (20–70%) compared to other components present in trace amounts [101]. Most essential oils are composed of terpenes, terpenoids, and other aromatic and aliphatic constituents with low molecular weights. Terpenes or terpenoids are synthesized within the cytoplasm of the cell through the mevalonic acid pathway [15]. Terpenes are composed of isoprene units and are generally represented by the chemical formula (C5H8)n. Terpenes can be acyclic, monocyclic, bicyclic, or tricyclic [102]. Owing to the diversity in their chemical structures, terpenes are classified into several groups such as monoterpenes (C10H16), sesquiterpenes (C15H24), diterpenes (C20H32), and triterpenes (C30H40). The major component (~90%) of bioactive essential oils is constituted of monoterpenes [103]. Some of the major compounds include monoterpene hydrocarbons (p-cymene, limonene, α-pinene, and α-terpinene), oxygenated monoterpenes (camphor, carvacrol, eugenol, and thymol), diterpenes (cembrene C, kaurene, and camphorene), sesquiterpene hydrocarbons (β-caryophyllene, germacrene D, and humulene), oxygenated sesquiterpenes (spathulenol, caryophyllene oxide), monoterpene alcohols (geraniol, linalool, and nerol), sesquiterpene alcohol (patchoulol), aldehydes (citral, cuminal), acids (geranic acid, benzoic acid), ketones (acetophenone, benzophenone), lactones (bergapten), phenols (eugenol, thymol, carvacrol, and catechol), esters (bornyl acetate, ethyl acetate), and coumarins (fumarin, benzofuran) [1, 4, 8, 13, 104, 105]. The structures of some of these compounds are represented in Figure 1. The major and biologically important chemical constituents of MAPs are shown in Tables 1, 2, and 3.Table 1
Chemical composition of various essential oils and their antibacterial activity against human pathogens.
MAPs Part used Major chemical compounds Inhibited microorganisms References Achillea clavennae Leaves and flowers Camphor, myrcene, 1,8-cineole,β-caryophyllene, linalool, geranyl acetate Klebsiella pneumonia, Streptococcus pneumonia, Haemophilus influenzae, Pseudomonas aeruginosa [18]  Achillea fragrantissima Aerial parts Yomogi alcohol, 1,8-cineole, artemisia alcohol, thujone Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli [19]  Achillea ligustica Aerial parts Viridiflorol, terpinen-4-ol Streptococcus mutans [20]  Artemisia absinthium Aerial parts Myrcene,trans-thujone, trans-sabinyl acetate E. coli, S. aureus, Staphylococcus epidermidis [21]  Artemisia biennis Aerial parts (Z)-Beta-ocimene, (E)-beta-farnesene, acetylenes, (Z)- and (E)-En-yn-dicycloethers E. coli, S. aureus, S. epidermidis [21]  Artemisia cana Aerial parts Santolina triene, alpha-pinene, camphene E. coli, S. aureus, S. epidermidis [21]  Artemisia dracunculus Aerial parts Methylchavicol, methyl eugenol, beta-phellandrene, terpinolene E. coli, S. aureus, S. epidermidis, Brochothrix thermosphacta, Listeria innocua, L. monocytogenes, Pseudomonas putida, Shewanella putrefaciens [21, 22]  Artemisia longifolia Aerial parts Alpha-pinene, camphene, 1,8-cineole E. coli, S. aureus, S. epidermidis [21]  Artemisia frigida Aerial parts 1,8-Cineole, methylchavicol, camphor E. coli, S. aureus, S. epidermidis [21]  Cinnamomum zeylancium Bark, leaves Cinnamaldehyde Enterobacteriaceae,S. aureus, Streptococcus pyogenes, S. pneumoniae, Enterococcus faecalis, E. faecium, Bacillus cereus, Acinetobacter lwoffii, Enterobacter aerogenes, E. coli, Klebsiella pneumoniae, Proteus mirabilis, P. aeruginosa, Salmonella typhimurium, Clostridium perfringens, Mycobacterium smegmatis [23, 24]  Copaifera officinalis Essential oil β-Caryophyllene, β-bisabolene, germacrene B, α-copaene, germacrene D, α-humulene, δ-cadinene S. aureus, E. coli [25]  Coriandrum sativum Leaves 2E-Decenal, decanal, 2E-decen-1-ol, n-decanol S. aureus, Bacillusspp., E. coli, Salmonella typhi, K. pneumonia, Proteus mirabilis, P. aeruginosa [26, 27]  Cuminum cyminum Leaves γ-Terpin-7-al, γ-terpinene, β-pinene, cuminaldehyde S. typhimurium, E. coli [28]  Cymbopogon citratus Fruit Ethanolic compounds Enterobacteriaceae,S. aureus [29]  Cymbopogon nardus Leaves, stems Δ2-Carene, beta-citronellal Brochothrix thermosphacta, E. coli, Listeria innocua, L. monocytogenes, P. putida, S. typhimurium, S. putrefaciens [22]  Cyperus longus Arial part β-Himachalene, α-humulene, γ-himachalene S. aureus, L. monocytogenes, L. monocytogenes, E. faecium, S. Enteritidis, E. coli, P. aeruginosa [30]  Daucus littoralis Leaves, stems, roots, flowers, fruits Germacrene D, acorenone B S. aureus, E. coli [31]  Dracocephalum foetidum Leaves n-Mentha-1,8-dien-10-al, limonene, geranial, neral B. subtilis, S. aureus, M.luteus, E. hirae, S. mutans, E. coli [32]  Eremanthus erythropapps Leaves (Z)-Caryophyllene, germacrene D, viridiflorol,p-cymene, γ-terpinene S. epidermidis [33]  Eugenia caryophyllata Flower buds Phenylpropanoids such as carvacrol, thymol, eugenol, cinnamaldehyde S. epidermidis [34]  Euphrasia rostkoviana Essential oil n-Hexadecanoic acid, thymol, myristic acid, linalool E. faecalis, E. coli, K. pneumoniae, S. aureus, S. epidermidis, P. aeruginosa [35]  Foeniculum vulgare Leaves Trans-anethole, methylchavicol, limonene S. typhimurium, E. coli [28]  Fortunella margarita Leaves Gurjunene, eudesmol, muurolene B. subtilis, S. aureus, Sarcina luta, S. faecalis, E. coli, K. pneumonia, P. aeruginosa [36]  Juniperus phoenicea Arial part α-Pinene, β-phellandrene, α-terpinyl acetate S. aureus, L. monocytogenes, L. monocytogenes, E. faecium, S. Enteritidis, E. coli, P. aeruginosa [30]  Laurus nobilis Arial part Eucalyptol (1,8-cineole), linalool Mycobacterium smegmatis, E. coli [37]  Lavandula x intermedia “Provence” (Blue Lavandin) (a cross betweenL. angustifolia, L. Latifolia) Arial part Camphor, eucalyptol (1,8-cineole), linalool,β-pinene, α-pinene M. smegmatis, E. coli [37]  Juniperus excelsa Leaves and twigs α-Pinene, α-cedrol, δ-car-3-ene S. aureus [38]  Lippia sidoides Leaves Thymol and carvacrol S. mutans, S. sanguis, S. salivarius, S. mitis [39]  Mentha piperita Arial part  S. aureus, S. typhimurium, V. parahaemolyticus [40]  Mentha pulegium Arial part Piperitone, piperitenone,α-terpineol, pulegone S. aureus, S. epidermidis, B. cereus, L. monocytogenes, E. coli, S. typhimurium, V. cholera, L. monocytogenes, E. faecium, S. Enteritidis [30]  Mentha suaveolens Arial part Pulegone, piperitone, cis-cis-p-menthenolide, limonene germacrene Lactococcus lactis subsp. Lactis, S. xylosus [41]  Melaleuca alternifolia(tea tree oil) Essential oil Terpinen-4-ol, 1,8-cineole,γ-terpinene, α-terpinene, terpinolene E. coli, S. aureus, S. epidermidis, E. faecalis, P. aeruginosa, M. avium, H. influenzae, S. pyogenes, S. pneumonia [42, 43]  Momordica charantia Seed Trans-nerolidol, apiole, cis-dihydrocarve,ol germacrene D E. coli, S. aureus [44]  Myrtus communis Leaves Eugenol,α-terpineol, γ-terpinene S. aureus, L. monocytogenes, E. durans, Salmonella Typhi, E. coli, B. subtilis, M. tuberculosis, P. aeruginosa, K. pneumonia, M. aviumsubsp. paratuberculosis, E. cloacae [30, 45]  Nigella sativa Seeds Thymoquinone,p-cymene, α-thujene, thymohydroquinone, longifolene S.  aureus, B.  cereus, E. coli, P. aeruginosa [46]  Ocimum gratissimum Leaves Eugenol, methyl eugenol, cis-ocimene, trans-ocimene,α-pinene, camphor S. aureus, Bacillusspp. E. coli, P. aeruginosa,S. typhi, K. pneumoniae, P. mirabilis, E. cloacae [26, 47]  Ocimum kilimandscharicum Flowers and leaves Eugenol, borneol, linalool, methyl eugenol B. subtilis, S. aureus, Citrobacter youngae,E. coli, Klebsiellaspp., Micrococcusspp., Proteusspp., Pseudomonasspp., Salmonella spp. [48]  Origanum vulgare Leaves, Arial part Carvacrol, thymol,γ-terpinene, trans-sabinene hydrate, cis-piperitol, borneol, terpinen-4-ol, linalool Clostridium botulinum, C. perfringens, L. monocytogenes,E. coli, S. choleraesuis, S. typhimurium, S. aureus, B. subtilis, Pseudomonas aeruginosa, Shigella sonnei,Sarcina lutea, M. flavus, K. pneumoniae, K. oxytoca [49–56]  Ocimum basilicum Leaves, stems γ-Terpinene, methylchavicol Brochothrix thermosphacta, E. coli, L. innocua, L. monocytogenes, P. putida, S. typhimurium, S. putrefaciens, M. flavus [22, 57]  Petroselinum sativum Leaves, stems Myristicin, apiol, 1,2,3,4-tetramethoxy-5-(2-propenyl)- benzene B. thermosphacta, E. coli, L. innocua, L. monocytogenes, P. putida, S. typhimurium, S. putrefaciens [22]  Piper nigrum Essential oil Limonene,δ-3-carene, α-pinene, β-caryophyllene, β-pinene, sabinene, α-felandeno, myrcene, para-cymene, linalool, terpinolene, β-selinene, 1,8 cineole, α-terpinene, α-humulene, α-copaene, eugenol, terpinen-4-ol, camphene, safrole S. aureus, E. coli [25]  Pimpinella anisum Seed Trans-anethole S. typhimurium, E. coli [58]  Plectranthus barbatus Leaves (Z)-Caryophyllene, germacrene D, viridiflorol,p-cymene, γ-terpinene S. epidermidis [4, 33]  P. amboinicus Leaves (Z)-Caryophyllene, germacrene D, viridiflorol,p-cymene, γ-terpinene S. epidermidis [4, 33]  Plectranthus neochilus Leaves α-Pinene, β-pinene, trans-caryophyllene, caryophyllene oxide E. faecalis, S. salivarius, S. sobrinus, S. sanguinis, S. mitis, L. casei, S. mutans [4, 59]  Pogostemon cablin Leaves Patchoulol,δ-guaieno; gurjunene-α, α-guaiene, aromadendrene, β-patchoulene K. pneumonia, H. pylori, E. coli, B. subtilis, S. aureus, P. aeruginosa, E. faecalis [1, 60–64]  Rosmarinus officinalis Leaves, flower Camphor, camphene, limonene, geraniol, myrcene, linalool benzoylacetate, linalool,α-pinene, α-terpinolene, bornyl acetate, borneol E. coli, S. typhimurium, B. cereus, Bacillus subtilis, S. aureus, S. agalactiae, S. epidermidis, S. aureus, P. vulgaris, P. aeruginosa, K. pneumonia, E. faecalis, B. thermosphacta, L. innocua, L. monocytogenes, P. putida, S. typhimurium, S. putrefaciens, M. smegmatis [22, 37, 65, 66]  Satureja hortensis Arial part Carvacrol, thymol,γ-terpinene C. botulinum, C. perfringens, [49]  Salvia sclarea Arial part Linalool, linalyl acetate, geranyl acetate,β- ocimene acetate, caryophyllene oxide S. aureus, S. agalactiae, S. epidermis, E. coli, Proteus vulgaris, P. aeruginosa, K. pneumonia, E. faecalis, B. pumilus, B. subtilis, S. typhimurium [67–70]  Salvia officinalis Arial part α-Thujone, camphor, 1,8-cineole, α-pinene S. aureus, P. stuartii, P. stuartii, E. coli, Shigella sonnei,Sarcina lutea, M. flavus, B. thermosphacta, E. coli, L. innocua, L. monocytogenes [17, 22, 70]  Salvia lavandulifolia Essential oil Camphor,α-thujone, beta-thujone, camphene, α-pinene, terpineol P. vulgaris, P. aeruginosa, K. pneumonia, E. faecalis [68, 70]  Satureja cuneifolia Aerial parts Carvacrol andp-cymene E. coli, Campylobacter jejuni, S. sonnei, S. aureus, L. monocytogenes, B. cereus, P. aeruginosa, S. enteritidis [71]  Struchium sparganophora Leaves β-Caryophyllene, germacrene A, α-humulene, germacrene D S. typhi, B. cereus, P. mirabilis, P. aeruginosa, B. subtilis [72]  Syzygium aromaticum Leaves, flower bud Eugenol, eugenylacetate P. aeruginosa, Enterobacteriaceae [22, 25]  Syzygium cumini Leaves α-Pinene, β-pinene, trans- caryophyllene, 1,3,6-octatriene, delta-3-carene, α-caryophyllene, α-limonene E. coli, S. aureus, P. aeruginosa, N. gonorrhoeae, B. subtilis, S. aureus [73]  Trachyspermum ammi Seeds — K. pneumoniae, E. coli, S. aureus [74]  Thymus vulgaris Arial part Thymol, linalool, carvacrol, 1,8-cineole, eugenol, camphor, camphene,α-pinene, borneol, β-pinene L. monocytogenes, E. coli,S. typhimurium, S. aureus, C. botulinum, C. perfringens, S.  sonnei,S. lutea, M.  flavus, B. thermosphacta, L. innocua, L. monocytogenes, P. putida, S. putrefaciens [22, 40, 49, 53, 54, 75, 76]  Thymus zygis Essential oil — S. choleraesuis, S. typhimurium, E. coli [50]  Thymus mastichina Leaves, stems m-Thymol, carvacrol, trans-caryophyllene B. thermosphacta, E. coli, L. innocua, L. monocytogenes, P. putida, S. typhimurium, S. putrefaciens [22]  Thymus kotschyanus Arial part Carvacrol, 1,8 cineole, thymol, borneol, E-caryophyllene S. aureus, S. epidermidis, B. cereus, E. coli [77]  Thuja sp. (Thuja plicata, Thuja occidentalis) Essential oil Alpha-thujone and beta-thujone P. aeruginosa, K. pneumoniae, S. aureus, E. coli [68]  Verbena officinalis Arial part Borneol, geranoil S. aureus, E. coli, S. typhimurium, L. monocytogenes [78]  Warionia saharae Arial part β-Eudesmol, trans-nerolidol, linalool, 1,8 cineole, camphor, p-cymene, terpinen-4-ol S. aureus, B. cereus, P. aeruginosa, E. coli [79]Table 2
Chemical composition of various essential oils and their antifungal activity against human pathogens.
MAPs Part used Major chemical compounds Inhibited microorganisms References Aegle marmelos Leaves γ-Cadinene, δ-carene, α-pinene Candida albicans, Aspergillus niger, Fusarium oxysporum [36]  Artemisia biennis Aerial parts (Z)-β-Ocimene, (E)-beta-farnesene, acetylenes, (Z)- and (E)-en-yn-dicycloethers Cryptococcus neoformans, Fonsecaea pedrosoi, A. niger [21]  Cinnamomum zeylancium Bark, leaves Cinnamaldehyde C. albicans, C. parapsilosis, C. krusei [23, 24]  Coriandrum sativum Leaves 2E-Decenal, decanal, 2E-decen-1-ol, n-decanol C. albicans [26, 27]  Daucus littoralis Leaves, stems, roots, flowers, fruits Germacrene D, acorenone B C. albicans [80]  Dracocephalum foetidum Leaves n-Mentha-1,8-dien-10-al, limonene, geranial, neral C. albicans [32]  Eremanthuserythropappus Leaves (Z)-Caryophyllene, germacrene D, viridiflorol,p-cymene, γ-terpinene C. albicans, C. gattii, C. gattii, C. neoformans, S. cerevisiae [33]  Euphrasia rostkoviana Essential oil n-Hexadecanoic acid, thymol, myristic acid, linalool C. albicans [35]  Feoniculum vulgare Seed Trans-anethole, methylchavicol, limonene Alternaria alternata, F. oxysporum, A. flavus [81]  Fortunella margarita Leaves Gurjunene, eudesmol, muurolene A. niger, C. albicans [36]  Glechon spathulata Leaves β-Caryophyllene, bicyclogermacrene Trichophyton rubrum, Epidermophyton floccosum [82]  Glechon marifolia Leaves β-Caryophyllene, bicyclogermacrene T. rubrum, E. floccosum [82]  Lippia sidoides Leaves Thymol and carvacrol C. albicans [39]  Melaleuca alternifolia (tea tree oil) Essential oil Terpinen-4-ol, 1,8-cineole,γ-terpinene, α-terpinene, terpinolene Alternaria spp. A. flavus, A. fumigates, A. niger, Blastoschizomyces Capitatus, C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, Cladosporiumspp., C. neoformans, Epidermophyton floccosum, Fusariumspp., Malassezia furfur, Microsporum canis, M. sympodialis, M. gypseum, Penicilliumspp., Rhodotorula rubra, Saccharomyces cerevisiae,Trichophyton mentagrophytes, T. rubrum, T. tonsurans, Trichosporonspp. [42, 81, 83, 84]  Mentha pulegium Arial part Piperitone, piperitenone,α-terpineol pulegone A. niger, C. albicans, C. zemplinina, Kloeckera apiculata, Metschnikowia pulcherrima, Tetrapisispora phaffii [30, 41]  Momordica charantia Seed Trans-nerolidol, apiole, cis-dihydrocarveol, germacrene D C. albicans [44]  Myrtus communis Leaves Eugenol,α-terpineol, γ-terpinene, α-caryophyllene C. albicans, A. flavus [45, 85–87]  Nigella sativa Seeds Thymoquinone,p-cymene, α-thujene, thymohydroquinone, longifolene A.  flavus, Fusarium moniliforme, F.  graminearum, P.  viridicatum [46, 62]  Ocimum species (Ocimum basilicum, Ocimum gratissimum, O. kilimandscharicum, O. lamiifolium, O. suave) Leaves, flower Eugenol, methyl eugenol, cis-ocimene, trans-ocimene,α-pinene camphor C. albicans, C. tropicalis, C. glabrata, P. notatum, R. stolonifer, M. mucedo, A. ochraceus, A. versicolor, A. niger, A. fumigates, T. viride, P. funiculosum [26, 27, 47, 48, 57]  Origanum vulgare Leaves, arial part Carvacrol, thymol,γ-terpinene, trans-sabinene hydrate, cis-piperitol, borneol, terpinen-4-ol, linalool C. albicans, A. niger, M. gypseum, M. canis, A. cajetani, T. violaceum, T. mentagrophytes, E. floccosum, T. rubrum, T. tonsurans, phytopathogens B. cinerea and P. oryzae [52, 56, 88]  Pelargonium graveolens Leaves Citronellol, citronellyl formate, geraniol C. tropicalis [89]  Plectranthus barbatus and P. amboinicus Leaves (Z)-Caryophyllene, germacrene D, viridiflorol,p-cymene, γ-terpinene C. albicans, C. gattii, C. gattii, C. neoformans, S. cerevisiae. [4, 33]  Pogostemon cablin Leaves Patchoulol,δ-guaieno; gurjunene-α, α-guaiene, aromadendrene, β-patchoulene Aspergillus species,C. albicans [1, 90, 91]  Rosmarinus officinalis Leaves Camphor, camphene, limonene, geraniol, myrcene, linalool benzaylacetate, linalool,α-pinene, α-terpinolene, bornyl acetate, borneol C. albicans,M. gypseum, M. canis, A. cajetani, T. violaceum, T. mentagrophytes, E. floccosum, T. rubrum, T. tonsurans, phytopathogens B. cinerea, P. oryzae [65, 88]  Salvia sclarea Arial part Linalool, linalyl acetate, geranyl acetate,β- ocimene acetate, caryophyllene oxide C. albicans, C. tropicalis, C. krusei, C. glabrata, C. parapsilosis [39, 84]  Syzygium aromaticum Leaves Eugenol, eugenylacetate A. fumigatus, C. albicans,Candidaspp. [25, 92]Table 3
Chemical composition of various essential oils and their antiviral activity against human pathogens.
Plant Part used Chemical compounds Inhibited microorganisms References Achillea fragrantissima Aerial parts 2,5,5-Trimethyl-3,6-heptadien-2-ol, eucalyptol, artemisia alcohol, thujone ORF virus (a parapox virus) [19]  Artemisia arborescens Aerial parts β-Thujone, linalool, myrcene, carvacrol Herpes simplex virus type 1 (HSV-1) [93]  Fortunella margarita Leaves Gurjunene, eudesmol, muurolene Avian influenza A virus (H5N1), [94]  Glechon spathulata Leaves β-Caryophyllene, bicyclogermacrene HSV-1 [82]  Glechon marifolia Leaves β-Caryophyllene, bicyclogermacrene HSV-1 [82]  Hyptis mutabilis Leaves α-Phellandrene, p-cymene, E-caryophyllene HSV-1 [95]  Lepechinia salviifolia Leaves Germacrene D HSV-1 [95]  Melissa officinalis Leaves Myrcene, linalool, camphor, citronellal,β-caryophyllene, caryophyllene oxide, citral HSV-2, avian influenza virus (AIV) subtype H9N2 [19, 96]  Minthostachys mollis Leaves α-Pinene, estragole HSV-1 [95]  Ocimum campechianum Leaves Linalool, eugenol HSV-1 [95]  Pogostemon cablin Leaves Patchoulol,δ-guaieno; gurjunene-α, α-guaiene, aromadendrene, β-patchoulene Influenza A (H2N2) virus [1, 97–99]  Trachyspermum ammi Leaves Thymol,α-pinene, p-cymene, limonene Japanese encephalitis virus (JEV) [100]Figure 1
Structures of some important chemical compounds of essential oils.The chemical constituents of plant essential oils differ between species. Some factors that can affect these constituents include the geographical location, environment, and stage of maturity [4, 106]. This chemical difference is directly related to differences in antimicrobial activities against various pathogenic microorganisms [107]. For example, the major chemical constituents of origanum essential oil (carvacrol and thymol) were shown to differ in their origin as well as antimicrobial property.Furthermore, the stereochemical properties of essential oils can vary and depend upon the method of extraction [108]. However, extraction products may also vary qualitatively and quantitatively in their composition [109]. Although essential oils can be recovered using fermentation, extraction, or effleurage processes, commercial production is preferably achieved by the steam distillation process [1, 4, 110]. Likewise, the antimicrobial efficiency of essential oils depends on the type of microbes to be inhibited as well as the evaluation methods, including bioautography, diffusion, and dilution [111, 112]. Methods to evaluate the essential oil chemistry, their biological activities, and various factors that affect bioactivity are detailed in the literature [110, 112, 113].


## 3. Antimicrobial Effects of Essential Oils

The antimicrobial effects of essential oils derived from MAPs are the basis of copious applications, in various revenue generating sectors such as pharmaceutical, nutraceutical, cosmetic, perfume, agronomy, and sanitary industries [1–3]. In the following section, we have broadly discussed the antibacterial, antifungal, and antiviral effects of essential oils obtained from MAPs.


### 3.1. Antibacterial Effects of Essential Oils

At present, many antibiotics are available for treating various bacterial pathogens. However, increased multidrug resistance has led to the increased severity of diseases caused by bacterial pathogens. In addition, low immunity in host cells and the ability of bacteria to develop biofilm-associated drug resistance have further increased the number of life-threatening bacterial infections in humans [114]. Thus, bacterial infections remain a major causative agent of human death, even today. In addition, the use of several antibacterial agents at higher doses may cause toxicity in humans. This has prompted researchers to explore alternative new key molecules against bacterial strains [115]. In this regard, plant essential oils and their major chemical constituents are potential candidates as antibacterial agents. Several types of essential oils and their major chemical constituents from various MAPs have been reported to possess a wide range of bacterial inhibitory potentials (Table 1).The effect of antibacterial activity of essential oils may inhibit the growth of bacteria (bacteriostatic) or destroy bacterial cells (bactericidal). Nevertheless, it is difficult to distinguish these actions. In relation to this, antibacterial activity is more frequently measured as the minimum bactericidal concentration (MBC) or the minimum inhibitory concentration (MIC) [110]. Rapid antibacterial screening of essential oils is usually conducted using the agar diffusion technique, where essential oils are added to filter paper discs or holes, which are put in agar that has been uniformly inoculated with a bacterial strain. After incubating, the inhibition zone represents the antimicrobial action [111]. The effectiveness of essential oils differs from one type to another as well as against different target bacteria depending on their structure (Gram-positive and Gram-negative bacteria). For instance, sandalwood and vetiver oils exhibit higher inhibitory activity against Gram-positive bacteria; however, they fail to inhibit Gram-negative bacterial strains [83, 114]. The essential oils of cinnamon, clove, pimento, thyme, oregano, and rosemary were shown to possess strong antibacterial activity againstSalmonella typhi,Staphylococcus aureus, andPseudomonas aeruginosa[116]. Clove oil was found to be the most effective among all the tested essential oils. The antimicrobial effect of these oils was correlated to the occurrence of the major compounds such as carvacrol, thymol, cinnamic aldehyde, eugenol, andp-cymene. Likewise, carvacrol, eugenol, and thymol obtained from MAPs have been shown to effectively inhibit food-borne pathogens such asEscherichia coli,Salmonella typhimurium,Listeria monocytogenes, andVibrio vulnificus[117]. The compounds such as benzoic acids, benzaldehydes, and cinnamic acid have shown up to 50% inhibition ofListeria monocytogenesunder anaerobic conditions [118]. Ouattara et al. [119] reported the antibacterial potential of clove, cinnamon, pimento, and rosemary essential oils against meat spoilage bacterial pathogens such asPseudomonas fluorescens,Serratia liquefaciens,Brochothrix thermosphacta,Carnobacterium piscicola,Lactobacillus curvatus, andLactobacillus sake. According to them, the 1/100 dilution of these essential oils was capable of inhibiting at least 5-6 of the tested microbes. The inhibitory effect of these oils was mainly correlated with the occurrence of eugenol and cinnamaldehyde in the essential oils. Other major compounds found were carvacrol, thymol, cinnamaldehyde, and camphor. Arora and Kaur [120] analyzed the antimicrobial activity of garlic, ginger, clove, black pepper, and green chilli on human pathogenic bacteria such asBacillus sphaericus,Enterobacter aerogenes,E. coli,Pseudomonas aeruginosa,S. aureus,Staphylococcus epidermidis,S. typhi, andShigella flexneri. They concluded that, among all these spices, the aqueous extract of garlic was sensitive against all the tested bacterial pathogens. The garlic extract inhibited 93% ofS. epidermidis andS. typhiwithin 3 h of incubation time. Similarly, the effect of clove extracts on the production of verotoxin byE. coliwas studied by Sakagami et al. [121], who found that verotoxin production was inhibited by the clove extract (MIC value of >1.0% w/v). The effectiveness of cardamom, anise, basil, coriander, rosemary, parsley, dill, and angelica essential oils against pathogenic and saprophytic microorganisms was examined by Elgayyar et al. [58]. They concluded that essential oils extracted from oregano, basil, and coriander plants have an inhibitory effect againstP. aeruginosa,S. aureus, andYersinia enterocolitica in the range of 400 ppm concentration. Skandamis et al. [122] observed the significance of oregano essential oils on the behavior ofS. typhimuriumin sterile and naturally contaminated beef fillets stored under aerobic and customized atmospheric conditions. The addition of oregano essential oils (0.8% v/w) reduced the majority of the tested bacterial pathogens. Hood et al. [23] reported that the bacterial growth may be suppressed by the ample use of essential oils or their use at high concentrations and that their mode of action results in the decline of bacterial cells. In another study,Achillea clavennae essential oil exhibited maximum inhibitory activity against respiratory disease-causing microbes likeKlebsiella pneumoniae,Streptococcus pneumoniae,Haemophilus influenzae, andP. aeruginosa [18]. The oil contained eucalyptol (1,8-cineole) and camphor as major compounds. According to Nevas et al. [49], pathogenic bacteria such asClostridium botulinum and Clostridium perfringens were effectively inhibited by oregano, savory, and thyme essential oils. The major compounds with an antibacterial effect were found to be camphor, thymol, and carvacrol. The essential oil ofSalvia officinalis contains α-thujone, camphor, and 1,8-cineole as the major chemical constituents and was shown to inhibit human bacterial pathogens such asS. aureusandProvidencia stuartii [67]. Some pathogenic bacteria (Salmonella choleraesuis,Salmonella enteritidis,S. typhimurium, andE. coli) were inhibited by the essential oils of thyme and oregano [50]. The essential oils showed an MIC value of 0.25% to ≥2% v/v. In another study,Salvia spp. (S. officinalis,S. sclarea, andS. lavandulifolia) andThuja spp. (T. plicataandT. occidentalis) essential oils exhibited potent antimicrobial properties against human pathogens [68]. The major components (α-thujone and β-thujone) of these sage species demonstrated high inhibitory activity againstP. aeruginosa andK. pneumoniae, whereasS. aureus andE. coliwere moderately inhibited.The antibacterial activity of oregano oil againstS. aureus,Bacillus subtilis,E. coli, andP. aeruginosa was reported by Santoyo et al. [51]. The MBC values ranged between 0.75 and 2.25 mg/mL. Carvacrol was the most effective compound with an MBC value of 0.75 to 1.53 mg/mL, followed by linalool with 1.04 to 1.75 mg/mL. Similarly, oregano essential oil was also shown to be effective againstProvidencia stuartiiandE. coli [52]. The essential oils ofThuja spp. (T. plicata andT. occidentalis) effectively inhibitedP. aeruginosa,K. pneumoniae,S. aureus, andE. coli[68]. Moreover, Chaieb et al. [34] revealed the antimicrobial potential of the essential oil ofEugenia caryophyllata against numerous multidrug-resistantS. epidermidis strains isolated from dialysis biomaterials. Saet et al. [32] reported the presence ofn-mentha-1,8-dien-10-al, limonene, geranial, and neral as the major constituents inDracocephalum foetidum essential oil. The oil exhibited antibacterial activity against human pathogenic bacteria such asS. aureus, B. subtilis, Enterococcus hirae,E. coli,Micrococcus luteus,Streptococcus mutans,andSaccharomyces cerevisiae. The MIC value ranged from 26 to 2592 μg/mL. Likewise, Botelho et al. [39] reported the antibacterial activity ofLippia sidoidesoil against four strains of cariogenic bacteria, namely,Streptococcus sanguis, S. mutans, Streptococcus salivarius, andStreptococcus mitis. The MIC value ranged from 0.625 to 10.0 mg/mL. Lopes-Lutz et al. [21] reported that several species ofArtemisia essential oil possessed strong activity againstE. coli,S. aureus, andS. epidermidis. Likewise,Momordica charantia seed essential oil exhibited inhibitory action againstE. coli andS. aureus with an MIC value of >500 and 125 μg/mL, respectively [44].The medicinal plantAchillea ligustica containing terpinen-4-ol, β-pinene, 1,8-cineole, and linalool showed effective inhibitory activity againstS. mutans with an MIC ranging from 155 to 625 μg/mL [20]. Many food-borne and spoilage bacterial pathogens were inhibited bySatureja cuneifolia essential oil and the MIC values were in the range of 600–1400 μg/mL [71]. The essential oil ofCoriandrum sativum demonstrated an antimicrobial potential against a wide range of bacterial pathogens, but the highest inhibition was found againstBacillus cereus andE. coli. The MIC of oil for Gram-positive bacteria was observed to be 108 mg/mL and, for Gram-negative bacteria, it ranged from 130 to 217 mg/mL [26]. Moreover, the essential oils extracted from thyme and mint leaves exhibited antibacterial activity against theS. aureus, S. typhimurium, Vibrio parahaemolyticus, L. monocytogenes, E. coli, C. botulinum, C. perfringens, Shigella sonnei, Sarcina lutea,andMicrococcus flavus [40, 75]. The Gram-negative bacterial strains showed more sensitivity towards the thyme oil. The MIC value ranged from 0.33 to 2.67 mg/mL [75]. The essential oil ofMyrtus communis was reported to inhibit various bacterial strains such asS. aureus, L. monocytogenes, Enterococcus durans, S. typhi,Enterobacter cloacae, E. coli, B. subtilis, Mycobacterium tuberculosis, P. aeruginosa, K. pneumoniae,andMycobacterium avium[85, 123]. Similarly, Unlu et al. [24] reported that diverse range of bacterial pathogens such asS. aureus, Streptococcus pyogenes, S. pneumoniae, Enterococcus faecalis, Enterococcus faecium, B. cereus, Acinetobacter lwoffii, E. aerogenes, E. coli, K. pneumoniae, Proteus mirabilis, P. aeruginosa, S. typhimurium, C. perfringens,andMycobacterium smegmatiswere inhibited by the essential oil ofCinnamomum zeylancium. In a study by Shan et al. [78], the essential oils of cinnamon, oregano, clove, pomegranate peels, and grape seeds were found to be effective againstS. enterica, but the clove extracts possessed the highest antibacterial activity.Melaleuca alternifolia (tea tree oil) and its major constituent, terpinen-4-ol, were shown to possess potential antibacterial properties against many pathogens includingE. coli, S. aureus, S. epidermidis, E. faecalis, P. aeruginosa, M. avium, H. influenzae, S. pyogenes,andS. pneumoniae. Overall, it was shown that tea tree oil and terpinen-4-ol have limited influence on the development of antibacterial resistance and susceptibility [42]. Ait-Ouazzou et al. [30] studied the essential oil composition and antibacterial potential ofMentha pulegium,Juniperus phoenicea, andCyperus longus and concluded that all these oils were effective against food-borne pathogens (S. aureus, L. monocytogenes, E. faecium, S. Enteritidis, E. coli,andP. aeruginosa). According to them,M. pulegium exhibited the best antibacterial activity compared toJ. phoenicea andC. longus. The MIC value ofM. pulegiumoil was <0.5 forE. faecium and 1 μL/mL forS. aureus, L. monocytogenes,E. coli, andS. enteritidis. Lawal et al. [124] have reported the antibacterial activity of essential oil ofOcimum gratissimum, O. kilimandscharicum,O. lamiifolium, andO. suave againstS. aureus, Bacillussp.,E. coli, P. aeruginosa, S. typhi, K. pneumoniae,andP. mirabilis. The MIC values varied between 1.25 and 10 mg/mL (flower oil) and between 0.16 and 10 mg/mL (leaf oil). The thyme oil obtained from leaves showed the presence of camphor, camphene, α-pinene, 1,8-cineole, borneol, and β-pinene, which exhibited effective antibacterial activity againstS. aureus, S. epidermidis, Streptococcussp., Pantoasp., andE. coli[53, 76]. The thyme oil showed MIC and MBC values of 627.7 μg/mL and 990.2 μg/mL, respectively, against theE. coli strain. The major compound thymol showed MIC and MBC values of 2786 μg/mL and 2540 μg/mL, respectively. Therefore, this study proposes the possible use of thyme oil as a potential antimicrobial agent for food preservation [76]. The oil obtained fromLaurus nobilis andLavandula intermediashowed inhibitory potential againstMycobacterium smegmatisandE. coli [37]. The bacterial strains (Shigella sonnei, Sarcina lutea,andMicrococcus flavus) were inhibited by the essential oil ofOriganum vulgare [54]. The zone of inhibition and MIC values ofO. vulgare oil were in the range of 9–36 mm and 125–600 μg/mL, respectively. Several food-borne pathogens such asBrochothrix thermosphacta, E. coli, Listeria innocua, L. monocytogenes, Pseudomonas putida, S. typhimurium,andShewanella putrefaciens were inhibited by some commercial essential oils including those ofOcimum basilicum,Petroselinum sativum, andRosmarinus officinalis [22]. The essential oil ofSyzygium cumini was found to contain α-pinene, β-pinene,trans-caryophyllene, 1,3,6-octatriene, delta-3-carene, α-caryophyllene, and limonene as major chemical compounds and possessed effective antibacterial activity against pathogenic bacterial strains such asE. coli, S. aureus, P. aeruginosa, Neisseria gonorrhoeae,B. subtilis, and S. aureus [73]. The essential oil exhibited moderate inhibition zones (12–14 mm) against the tested microbes. Andrade et al. [25] studied the antimicrobial activity of 27 different essential oils employed in aromatherapy procedures and found thatPiper nigrum, Melaleuca alternifolia, Copaifera officinalis,andCinnamomum cassiaessential oils were effective againstS. aureus andE. coli, whereasS. aromaticum essential oil was efficient againstP. aeruginosa strains. Khoury et al. [38] have reported thatJuniperus excelsa essential oil obtained from leaves and twigs was efficient at inhibitingS. aureus (MIC value of 64 mg/ml) andTrichophyton rubrum (MIC value of 128 mg/mL). Although the essential oil ofMentha suaveolens showed strong antibacterial activity againstS. xylosus with an MIC value of 14.4 μL/mL, it showed no activity against lactic acid bacterial strains exceptLactococcus lactis[41]. The essential oil of the herbStruchium sparganophora revealed the presence of β-caryophyllene, germacrene A, α-humulene, and germacrene D as major chemical constituents and it exhibited antibacterial activity againstS. typhi, B. cereus, B. subtilis, P. mirabilis,andP. aeruginosa[72]. The inhibitory zone for leaf oil ranged from 9.0±1.0 to 14.3±2.55 mm, whereas the essential oil from stem had inhibitory activity ranging from 18.5±2.2 to 20.0±0.0 mm.Daucus littoralis oil obtained from different parts of the plant has showed a strong antibacterial activity againstE. coliandS. aureus with an MIC value ranging from 20 to 40 μL/mL [31]. Likewise, Beatovic et al. [57] have reported the antibacterial activity ofOcimum basilicum oil againstS. typhimurium andE. coli. The MIC values ranged between 0.009 and 23.48 μg/mL, whereas the MBC values ranged from 0.28 to 135 μg/mL. In addition, essential oil of Australian-grownOcimum tenuiflorum (Tulsi) showed antibacterial activity against selected microbial pathogens including methicillin-resistantS. aureus(MRSA), E. coli,andP. aeruginosa with MIC values ranging from 2.25 to >4.5 μg/mL [125]. The essential oil ofPogostemon cablinwas shown to have effective antibacterial activity against many pathogenic bacterial strains includingE. coli, S. aureus, K. pneumoniae,andH. pylori [1, 60–64]. The GC-MS analysis of essential oils ofFoeniculum vulgare (Fennel) showed the occurrence oftrans-anethole, methylchavicol, limonene, and fenchone, whereasCuminum cyminum L. had γ-terpin-7-al, γ-terpinene, β-pinene, and cuminaldehyde as the major constituents. Both essential oils were effective againstS. typhimuriumandE. coli [28]. TheF. vulgare oil exhibited the lowest MIC values of 0.062 and 0.031% (v/v) againstE. coli andS. typhimurium, respectively, whereasC. cyminum oil showed MIC values of 0.250 and 0.125% (v/v) againstE. coli andS. typhimurium, respectively. The bacterial strainsS. aureus, B. cereus,andP. aeruginosawere strongly inhibited by the essential oil ofWarionia saharae,which contained β-eudesmol,trans-nerolidol, linalool, 1,8-cineole, camphor,p-cymene, and terpinen-4-ol as major compounds [79]. The MICs ranged between 0.039 and 0.156 mg/mL for all tested bacterial strains. The essential oil extracted from seeds ofTrachyspermum ammishowed activity against all 36 clinical isolates ofK. pneumoniae, E. coli,andS. aureusisolated from patients suffering from urinary tract infections [74]. An MIC value of 250 ppm was observed forK. pneumoniae, whereas it was observed to be 100 ppm forE. coli andS. aureus. The seed essential oils ofNigella sativa containing thymoquinone,p-cymene, α-thujene, thymohydroquinone, and longifolene as major phytocompounds were shown to exhibit strong antibacterial activity againstB.  cereus, E.  coli, P. aeruginosa, andS.  aureus. The oil was highly effective againstB. cereus, B. subtilis, andS. aureusand showed a complete zone of inhibition at 3000 ppm concentration. Moreover, the zones of inhibition forP. aeruginosa andE. coli were 20 and 25 mm, respectively [126]. A study by Cui et al. [69] has shown thatSalvia sclareaoil showed a considerable inhibitory potential against the growth ofE. coli, S. aureus, Bacillus pumilus, K. pneumoniae, B. subtilis, S. typhimurium,andP. aeruginosa with MIC and MBC of 0.05 and 0.1%, respectively. Ahmadi et al. [77] reported the antibacterial properties ofThymus kotschyanus essential oil againstB. cereus,E. coli, S. aureus, andS. epidermidis.The MIC values for these pathogens ranged from 0.097 to 6.25 μL/mL. The antibacterial activity ofEuphrasia rostkoviana essential oil againstE. faecalis,E. coli,K. pneumoniae,S. aureus,S. epidermidis, andP. aeruginosa was reported by Novy et al. [35]. In the study, all Gram-positive bacteria were effectively inhibited with an MIC of 512 μg/mL. The bacterial strainS. epidermidis was inhibited by the essential oils ofPlectranthus barbatus andP. amboinicus with an MIC value of 31 μg/mL [4, 33]. Likewise, the essential oil ofPlectranthus neochilus was shown to inhibit some cariogenic bacteria such asE. faecalis, S. salivarius, Streptococcus sobrinus, Streptococcus sanguinis, S. mitis, S. mutans,andLactobacillus casei[59]. The essential oil displayed moderate antibacterial activity againstE. faecalis(MIC=250μg/mL) andS. salivarius(MIC=250μg/mL). Meanwhile,S. sobrinus (MIC=62.5μg/mL),S. sanguinis (MIC=62.5μg/mL),S. mitis (MIC=31.25μg/mL), andLactobacillus casei (MIC=31.25μg/mL) were significantly inhibited. Interestingly, the MIC value forS. mutans was found to be 3.9 μg/mL. In another study, the essential oil ofFortunella margarita was shown to inhibitStreptococcus faecalis andP. aeruginosa significantly with inhibitory zones of 30 mm and 28 mm, respectively. In addition, moderate activity was observed forB. subtilis, S. aureus, Sarcina lutea,andE. coliwith inhibitory zones ranging from 20 to 25 mm [36]. Similarly,Achillea fragrantissima essential oil was effective againstS. aureus,S. epidermidis, andE. coli with the highest inhibition zone of 26 mm, 16 mm, and 16 mm, respectively [19]. In a study by Radaelli et al. [127], a major food-borne disease-causing agent,C. perfringens, was inhibited by essential oils of Brazilian MAPs such as basil, rosemary, marjoram, peppermint, thyme, andPimpinella anisum (anise). The MIC values were 1.25 mg/mL for thyme, 5.0 mg/mL for marjoram and basil, and 10 mg/mL for peppermint, rosemary, and anise. Mahmoud et al. [128] have shown the antimicrobial potential of 11 essential oils against all the tested microbes (S. aureus,E. coli, P. aeruginosa, andK. pneumoniae). Onion oil exhibited good antibacterial activity (MIC=12μg/mL) againstS. aureus. Chamomile (Anthemis nobilis) oil showed the best activity againstP. aeruginosa (MIC=5.1μg/mL). Origanum and chamomile oils showed the highest antibacterial activity (MIC7.2,7.5,and7.7μg/mL) againstE. coli.Origanum and ivy (Dolichos lablab) oils were effective againstK. pneumoniae with MIC values of 6.2 and 6.5 μg/mL, respectively. More recent studies have revealed that essential oils ofEucalyptus globulus, Matricaria chamomilla, Termitomyces schimperi,andR. officinalispossess antimicrobial activity againstS. aureus, S. pyogenes, S. typhi, Shigellaspp., E. coli,andP. aeruginosa[129]. The essential oil ofTermitomyces schimperi showed MIC values of <15.75 mg/mL for most of the tested bacteria, whereas other essential oils exhibited MIC values of 15.75–36.33 mg/mL against tested bacteria.


### 3.2. Antifungal Effects of Essential Oils

The essential oils and their constituents have been used against a broad range of fungal pathogens. Table2 summarizes various essential oils, their chemical compositions, and their antifungal activity against human pathogens. The essentials oils extracts from many plants such as basil, citrus, fennel, lemon grass, oregano, rosemary, and thyme have shown considerable antifungal activity against a wide range of fungal pathogens [65]. Arora and Kaur [120] observed the antimicrobial activity of essential oils extracted from spices against fungal pathogens. They found that garlic and clove extracts inhibited the growth ofCandida acutus, C. albicans, C. apicola, C. catenulata. C. inconspicua, C. tropicalis, Rhodotorula rubra, Saccharomyces cerevisiae,andTrigonopsis variabilis. Similarly, Grohs and Kunz [29] investigated mixtures of ground spices and demonstrated their efficacy against theC. lipolytica. According to the report of Ultee and Smid [55], oregano and thyme essential oils were some of the best inhibitors of fungal pathogens, because of the phenolic compounds (carvacrol and thymol) as main constituents, which disrupt fungal cell membranes. Likewise, Delaquis and Mazza [130] reported the antimicrobial effects of isothiocyanate isolated from the essential oils of onion and garlic plants. They stated that isothiocyanates may inactivate the extracellular enzymes through oxidative cleavage of disulfide bonds. Isothiocyanate was effective againstBotrytis, Fusarium, Penicillium, andCladosporium species. The antifungal activity of essential oils and their derivatives on the cell viability, mycelium growth, and mycotoxin-producing ability of molds has been studied [131]. It was concluded that, among all the tested essential oils, clove, cinnamon, and oregano essential oils were effective againstAspergillus parasiticus andFusarium moniliforme. The oil ofOriganum vulgare was efficient at inhibitingC. albicans,Aspergillus niger,Microsporum gypseum,Microsporum canis, Arthroderma cajetani, Trichophyton violaceum,Trichophyton mentagrophytes,Epidermophyton floccosum,T. rubrum, andTrichophyton tonsurans [52, 56]. The MIC values ranged from 0.625 to 10.0 mg/mL against all the tested microbes. The essential oils ofLippia sidoides,Rosmarinus officinalis,Salvia sclarea, andMomordica charantia were shown to inhibitC. albicans effectively [39, 44, 65]. Clove essential oil showed an MIC value of 0.125 and 0.062% (v/v) againstC. albicans andA. niger, respectively. Rosemary essential oil exhibited MIC values of 0.25 and 1.0% (v/v) againstC. albicans andA. niger, respectively [65]. Thymol and carvacrol effectively inhibitedC. albicans with inhibition zones of 10.6 and 9 mm, respectively [39].Similarly, Jirovetz et al. [70] analyzed the antifungal activity ofCoriandrum sativum oil againstCandida species. The essential oil obtained from leaves and flowers of theOcimumsp. showed considerable antifungal potential againstC. albicans, C. tropicalis, C. glabrata, Penicillium notatum, Rhizopus stolonifer, andMucor mucedo [27, 47, 48]. Likewise,Myrtus communis oil also inhibitedC. albicans, Aspergillus flavus, andFusarium culmorum [45, 85, 86]. The essential oils of thyme and clove completely inhibited the mycelial growth ofA. flavus when 3 μL of oil was added to the Petri-dish [86]. The MIC values ofM. communis oil were found to be 50 μL/mL forA. flavus and 30 μL/mL forA. ochraceus and F. culmorum [45]. In addition, Bouzabata et al. [87] analyzed the antifungal activity ofM. communis oil againstE. floccosum,Microsporum canis,Trichophyton rubrum(dermatophytes), andCryptococcus neoformans(yeast). An MIC value of 0.64 mg/mL was found to be lethal forM. canis,T. rubrum, andE. floccosum. However,Candida sp. andAspergillus sp. strains were relatively less inhibited, with MIC values of 1.25 mg/mL and 5 mg/mL, respectively. Tea tree oil(Melaleuca alternifolia) was effective against many fungal pathogens such asAlternariaspp.,A. flavus, A. fumigates, A. niger, Blastoschizomyces capitatus, C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, Cladosporiumspp.,Cryptococcus neoformans, E. floccosum, Fusariumspp., Malassezia furfur, Malassezia sympodialis, Microsporum canis, M. gypseum, Penicilliumspp.,Rhodotorula rubra, S. cerevisiae, T. mentagrophytes, T. rubrum, T. tonsurans,andTrichosporonsp. [81]. The essential oil ofSalvia sclarea, a medicinal plant, contained 56.88% linalyl acetate, 20.75% linalool, 5.08% germacrene D, and 3.41%  β-caryophyllene as the chief chemical compounds. The essential oil and the pure compounds (linalyl acetate and linalool) were shown to possess antifungal properties againstC. albicans, C. tropicalis, C. krusei, C. glabrata,andC. parapsilosis [84]. The antifungal activity ofPogostemon cablin oil againstAspergillus species andC. albicans has been reported by many authors [1, 90, 91]. MIC values of 0.064 mg/mL (cinnamon oil) and 0.032 mg/mL (pogostemon oil) forC. albicans, 0.129 mg/mL (cinnamon oil) and 0.064 mg/mL (pogostemon oil) forC. tropicalis, and 0.129 mg/mL (cinnamon oil) and 0.064 mg/mL (pogostemon oil) forC. krusei were observed [90]. The essential oils ofMentha pulegiumandM. suaveolens were efficient at inhibiting fungal species such asS. cerevisiae, Kloeckera apiculata, Candida zemplinina, Metschnikowia pulcherrima,andTetrapisispora phaffii [41]. The essential oil ofM. insularis showed the highest activity againstStaphylococcus xylosuswith an MIC value of 3.6 μL/mL. Moreover, Venturi et al. [82] reported the antifungal action of the essential oils extracted fromGlechon spathulata andG. marifolia against the dermatophytic fungiTrichophyton rubrum andEpidermophyton floccosum. The MIC values ranged from 10 to 83 mg/mL againstT. rubrum and 83 to 500 mg/mL againstE. floccosum. The essential oil ofDaucus littoralis was effective againstC. albicans with the MIC value ranging from 20 to 40 μL/mL [80]. Seed essential oil ofNigella sativa was shown to possess activity againstA.  flavus,F. moniliforme,Fusarium graminearum,andPenicillium viridicatum[46]. This oil was very effective and showed up to 90% zone inhibition againstF. moniliforme. Moreover, the dermatophytic fungusT. rubrum was repressed by the essential oil ofJ. excelsa and the MIC value was observed to be 128 mg/mL [38].More recently, eugenol (an essential oil compound from clove) was shown to cause permanent damage to the cells ofC. albicans and was considered to be an efficient antifungal agent. The MIC value of eugenol was found to be 1.0% v/v [92]. Beatovic et al. [57] have reported its antifungal potential againstOcimum basilicum,Aspergillus ochraceus, A. versicolor, A. niger, A. fumigates, Trichoderma viride,andP. funiculosum. Similarly, the inhibitory potential ofAegle marmelos oil againstC. albicans, A. niger,andF. oxysporumwas demonstrated. The essential oils extracted fromEremanthus erythropappus,P. barbatus,andP. amboinicus were shown to inhibit the growth ofC. albicans, Cryptococcus gattii, Cryptococcus neoformans, andS. cerevisiae [33]. Papajani et al. [88] have reported the antifungal activity of rosemary essential oil against dermatophytes such asA. cajetani,E. floccosum,M. gypseum,M. canis,T. violaceum,T. mentagrophytes,T. rubrum, andT. tonsurans and phytopathogens such asBotrytis cinerea andPleomorphomonas oryzae. According to them, concentration below 20 μg/mL was not effective and they suggested the use of concentrations above 100 μg/ml for better antifungal activity. The essential oil ofFortunella margarita exhibited activity againstA. nigerandC. albicans with a zone of inhibition of more than 30 mm [36]. In a recent study by Souza et al. [89], the essential oil ofPelargonium graveolens showed effective inhibitory potential againstC. tropicalis, a pathogen resistant to clinically used antifungal agents. The essential oil ofP. graveolens was found to be rich in geraniol and linalool. Four common essential oils of MAPs including litsea(Litsea cubeba), oregano, marjoram(Origanum majoranaL.), thymus, and their mixtures showed varied levels of antifungal activity againstC. albicans,C. tropicalis,C. krusei,C. guilliermondii,C. parapsilosis, andS. cerevisiae [132]. More recently, the essential oils obtained fromE. globulus, M. chamomilla, T. schimperi,andR. officinalis demonstrated effective antifungal activity againstTrichophytonspp.andAspergillusspp. [129].


### 3.3. Antiviral Effects of Essential Oils

Plant-based products and bioactive pure compounds may be a new source of antiviral drugs, as natural products have inherently high chemical diversity. Viral diseases are still a major problem for human health worldwide. So far, only a limited number of drugs are effective against many of these viruses, which has prompted research into finding new antiviral lead molecules. From our literature survey, it is evident that many essential oils possess antiviral properties against many DNA and RNA viruses, such as herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), dengue virus type 2, Junin virus, influenza virus adenovirus type 3, poliovirus, and coxsackievirus B1 [96, 105, 114, 133, 134].The antiviral activities of essential oils of major MAPs along with their constituents are detailed in Table3. The oregano and clove essential oils also exhibited strong antiviral activity against several nonenveloped RNA and DNA viruses such as adenovirus type 3, poliovirus, and coxsackievirus B1 [133, 134]. The replication capability of HSV-1 virus could be repressed by various essential oils under in vitro experimental conditions [135–137]. HSV-1 is the cause of common viral infections in humans, such as herpetic keratitis, herpetic encephalitis, mucocutaneous herpes infections, and neonatal herpes. Studies on the essential oils ofArtemisia arborescens, Glechon spathulata, andGlechon marifolia found that they strongly suppressed HSV-1 [82, 93, 138].Melissa officinalis essential oils have major constituents, namely, citral and citronellal, which could inhibit the replication of HSV-2 [96, 133, 137]. Likewise, the antiherpes activities of Australian tea tree oil, eucalyptus oil, and thyme oil have been previously reported [93, 135–138]. The major chemical constituent α-caryophyllene, which occurs in many essential oils of medicinal plants, is considered to be the best antiviral agent [135].Likewise, several phenylpropanoids and sesquiterpenes including eugenol, trans-anethole,β-eudesmol, β-caryophyllene, and farnesol, which are present in essential oils, also have antiviral properties against HSV [135]. Similarly, another major compound of essential oils, eugenol, showed virucidal activity against human herpesvirus [137, 139]. Some triterpenes and sesquiterpenes also possess antiviral activity against different herpesviruses and rhinovirus [140–143]. García et al. [144] reported the antiviral activity ofArtemisia douglasiana andEupatorium patens essential oils against the dengue virus. In addition,Lippia junellianaandLippia turbinate essential oils showed activity against the Junin virus. Anti-influenza A (H2N2) activity was exhibited by the essential oil compounds ofPogostemon cablin [1, 97–99] and the antiviral property of the essential oils obtained from fruits and leaves ofFortunella margarita exhibited potential activity against avian influenza A virus (H5N1) [94]. Roy et al. [100] indicated the potential antiviral activity ofTrachyspermum ammi oil against Japanese encephalitis virus (JEV). Similarly, Zeedan et al. [19] reported the antiviral activity ofAchillea fragrantissima against the ORF virus (a parapox virus). More recently, Pourghanbari et al. [145] evaluated in vitro antiviral activity ofM. officinalis (lemon balm) essential oil and oseltamivir and their synergistic effect on avian influenza virus (AIV) subtype H9N2. They found that various concentrations of lemon balm essential oil suppressed influenza virus replication. However, it had improved efficacy when coadministered with the antiviral agent oseltamivir. Essential oils obtained from Colombian MAPs such asLepechinia salviifolia,Minthostachys mollis,Hyptis mutabilis,Lepechinia vulcanicola, andOcimum campechianum were reported to possess antiviral activity against human herpes viruses types 1 and 2 [95]. They also reported that these essential oils inhibit viral activity during their early stages of infection. Thus, plant-based essential oils could be used as antiviral agents against several viral diseases in humans and have the potential to be used as alternatives to synthetic antiviral drugs.


## 3.1. Antibacterial Effects of Essential Oils

At present, many antibiotics are available for treating various bacterial pathogens. However, increased multidrug resistance has led to the increased severity of diseases caused by bacterial pathogens. In addition, low immunity in host cells and the ability of bacteria to develop biofilm-associated drug resistance have further increased the number of life-threatening bacterial infections in humans [114]. Thus, bacterial infections remain a major causative agent of human death, even today. In addition, the use of several antibacterial agents at higher doses may cause toxicity in humans. This has prompted researchers to explore alternative new key molecules against bacterial strains [115]. In this regard, plant essential oils and their major chemical constituents are potential candidates as antibacterial agents. Several types of essential oils and their major chemical constituents from various MAPs have been reported to possess a wide range of bacterial inhibitory potentials (Table 1).The effect of antibacterial activity of essential oils may inhibit the growth of bacteria (bacteriostatic) or destroy bacterial cells (bactericidal). Nevertheless, it is difficult to distinguish these actions. In relation to this, antibacterial activity is more frequently measured as the minimum bactericidal concentration (MBC) or the minimum inhibitory concentration (MIC) [110]. Rapid antibacterial screening of essential oils is usually conducted using the agar diffusion technique, where essential oils are added to filter paper discs or holes, which are put in agar that has been uniformly inoculated with a bacterial strain. After incubating, the inhibition zone represents the antimicrobial action [111]. The effectiveness of essential oils differs from one type to another as well as against different target bacteria depending on their structure (Gram-positive and Gram-negative bacteria). For instance, sandalwood and vetiver oils exhibit higher inhibitory activity against Gram-positive bacteria; however, they fail to inhibit Gram-negative bacterial strains [83, 114]. The essential oils of cinnamon, clove, pimento, thyme, oregano, and rosemary were shown to possess strong antibacterial activity againstSalmonella typhi,Staphylococcus aureus, andPseudomonas aeruginosa[116]. Clove oil was found to be the most effective among all the tested essential oils. The antimicrobial effect of these oils was correlated to the occurrence of the major compounds such as carvacrol, thymol, cinnamic aldehyde, eugenol, andp-cymene. Likewise, carvacrol, eugenol, and thymol obtained from MAPs have been shown to effectively inhibit food-borne pathogens such asEscherichia coli,Salmonella typhimurium,Listeria monocytogenes, andVibrio vulnificus[117]. The compounds such as benzoic acids, benzaldehydes, and cinnamic acid have shown up to 50% inhibition ofListeria monocytogenesunder anaerobic conditions [118]. Ouattara et al. [119] reported the antibacterial potential of clove, cinnamon, pimento, and rosemary essential oils against meat spoilage bacterial pathogens such asPseudomonas fluorescens,Serratia liquefaciens,Brochothrix thermosphacta,Carnobacterium piscicola,Lactobacillus curvatus, andLactobacillus sake. According to them, the 1/100 dilution of these essential oils was capable of inhibiting at least 5-6 of the tested microbes. The inhibitory effect of these oils was mainly correlated with the occurrence of eugenol and cinnamaldehyde in the essential oils. Other major compounds found were carvacrol, thymol, cinnamaldehyde, and camphor. Arora and Kaur [120] analyzed the antimicrobial activity of garlic, ginger, clove, black pepper, and green chilli on human pathogenic bacteria such asBacillus sphaericus,Enterobacter aerogenes,E. coli,Pseudomonas aeruginosa,S. aureus,Staphylococcus epidermidis,S. typhi, andShigella flexneri. They concluded that, among all these spices, the aqueous extract of garlic was sensitive against all the tested bacterial pathogens. The garlic extract inhibited 93% ofS. epidermidis andS. typhiwithin 3 h of incubation time. Similarly, the effect of clove extracts on the production of verotoxin byE. coliwas studied by Sakagami et al. [121], who found that verotoxin production was inhibited by the clove extract (MIC value of >1.0% w/v). The effectiveness of cardamom, anise, basil, coriander, rosemary, parsley, dill, and angelica essential oils against pathogenic and saprophytic microorganisms was examined by Elgayyar et al. [58]. They concluded that essential oils extracted from oregano, basil, and coriander plants have an inhibitory effect againstP. aeruginosa,S. aureus, andYersinia enterocolitica in the range of 400 ppm concentration. Skandamis et al. [122] observed the significance of oregano essential oils on the behavior ofS. typhimuriumin sterile and naturally contaminated beef fillets stored under aerobic and customized atmospheric conditions. The addition of oregano essential oils (0.8% v/w) reduced the majority of the tested bacterial pathogens. Hood et al. [23] reported that the bacterial growth may be suppressed by the ample use of essential oils or their use at high concentrations and that their mode of action results in the decline of bacterial cells. In another study,Achillea clavennae essential oil exhibited maximum inhibitory activity against respiratory disease-causing microbes likeKlebsiella pneumoniae,Streptococcus pneumoniae,Haemophilus influenzae, andP. aeruginosa [18]. The oil contained eucalyptol (1,8-cineole) and camphor as major compounds. According to Nevas et al. [49], pathogenic bacteria such asClostridium botulinum and Clostridium perfringens were effectively inhibited by oregano, savory, and thyme essential oils. The major compounds with an antibacterial effect were found to be camphor, thymol, and carvacrol. The essential oil ofSalvia officinalis contains α-thujone, camphor, and 1,8-cineole as the major chemical constituents and was shown to inhibit human bacterial pathogens such asS. aureusandProvidencia stuartii [67]. Some pathogenic bacteria (Salmonella choleraesuis,Salmonella enteritidis,S. typhimurium, andE. coli) were inhibited by the essential oils of thyme and oregano [50]. The essential oils showed an MIC value of 0.25% to ≥2% v/v. In another study,Salvia spp. (S. officinalis,S. sclarea, andS. lavandulifolia) andThuja spp. (T. plicataandT. occidentalis) essential oils exhibited potent antimicrobial properties against human pathogens [68]. The major components (α-thujone and β-thujone) of these sage species demonstrated high inhibitory activity againstP. aeruginosa andK. pneumoniae, whereasS. aureus andE. coliwere moderately inhibited.The antibacterial activity of oregano oil againstS. aureus,Bacillus subtilis,E. coli, andP. aeruginosa was reported by Santoyo et al. [51]. The MBC values ranged between 0.75 and 2.25 mg/mL. Carvacrol was the most effective compound with an MBC value of 0.75 to 1.53 mg/mL, followed by linalool with 1.04 to 1.75 mg/mL. Similarly, oregano essential oil was also shown to be effective againstProvidencia stuartiiandE. coli [52]. The essential oils ofThuja spp. (T. plicata andT. occidentalis) effectively inhibitedP. aeruginosa,K. pneumoniae,S. aureus, andE. coli[68]. Moreover, Chaieb et al. [34] revealed the antimicrobial potential of the essential oil ofEugenia caryophyllata against numerous multidrug-resistantS. epidermidis strains isolated from dialysis biomaterials. Saet et al. [32] reported the presence ofn-mentha-1,8-dien-10-al, limonene, geranial, and neral as the major constituents inDracocephalum foetidum essential oil. The oil exhibited antibacterial activity against human pathogenic bacteria such asS. aureus, B. subtilis, Enterococcus hirae,E. coli,Micrococcus luteus,Streptococcus mutans,andSaccharomyces cerevisiae. The MIC value ranged from 26 to 2592 μg/mL. Likewise, Botelho et al. [39] reported the antibacterial activity ofLippia sidoidesoil against four strains of cariogenic bacteria, namely,Streptococcus sanguis, S. mutans, Streptococcus salivarius, andStreptococcus mitis. The MIC value ranged from 0.625 to 10.0 mg/mL. Lopes-Lutz et al. [21] reported that several species ofArtemisia essential oil possessed strong activity againstE. coli,S. aureus, andS. epidermidis. Likewise,Momordica charantia seed essential oil exhibited inhibitory action againstE. coli andS. aureus with an MIC value of >500 and 125 μg/mL, respectively [44].The medicinal plantAchillea ligustica containing terpinen-4-ol, β-pinene, 1,8-cineole, and linalool showed effective inhibitory activity againstS. mutans with an MIC ranging from 155 to 625 μg/mL [20]. Many food-borne and spoilage bacterial pathogens were inhibited bySatureja cuneifolia essential oil and the MIC values were in the range of 600–1400 μg/mL [71]. The essential oil ofCoriandrum sativum demonstrated an antimicrobial potential against a wide range of bacterial pathogens, but the highest inhibition was found againstBacillus cereus andE. coli. The MIC of oil for Gram-positive bacteria was observed to be 108 mg/mL and, for Gram-negative bacteria, it ranged from 130 to 217 mg/mL [26]. Moreover, the essential oils extracted from thyme and mint leaves exhibited antibacterial activity against theS. aureus, S. typhimurium, Vibrio parahaemolyticus, L. monocytogenes, E. coli, C. botulinum, C. perfringens, Shigella sonnei, Sarcina lutea,andMicrococcus flavus [40, 75]. The Gram-negative bacterial strains showed more sensitivity towards the thyme oil. The MIC value ranged from 0.33 to 2.67 mg/mL [75]. The essential oil ofMyrtus communis was reported to inhibit various bacterial strains such asS. aureus, L. monocytogenes, Enterococcus durans, S. typhi,Enterobacter cloacae, E. coli, B. subtilis, Mycobacterium tuberculosis, P. aeruginosa, K. pneumoniae,andMycobacterium avium[85, 123]. Similarly, Unlu et al. [24] reported that diverse range of bacterial pathogens such asS. aureus, Streptococcus pyogenes, S. pneumoniae, Enterococcus faecalis, Enterococcus faecium, B. cereus, Acinetobacter lwoffii, E. aerogenes, E. coli, K. pneumoniae, Proteus mirabilis, P. aeruginosa, S. typhimurium, C. perfringens,andMycobacterium smegmatiswere inhibited by the essential oil ofCinnamomum zeylancium. In a study by Shan et al. [78], the essential oils of cinnamon, oregano, clove, pomegranate peels, and grape seeds were found to be effective againstS. enterica, but the clove extracts possessed the highest antibacterial activity.Melaleuca alternifolia (tea tree oil) and its major constituent, terpinen-4-ol, were shown to possess potential antibacterial properties against many pathogens includingE. coli, S. aureus, S. epidermidis, E. faecalis, P. aeruginosa, M. avium, H. influenzae, S. pyogenes,andS. pneumoniae. Overall, it was shown that tea tree oil and terpinen-4-ol have limited influence on the development of antibacterial resistance and susceptibility [42]. Ait-Ouazzou et al. [30] studied the essential oil composition and antibacterial potential ofMentha pulegium,Juniperus phoenicea, andCyperus longus and concluded that all these oils were effective against food-borne pathogens (S. aureus, L. monocytogenes, E. faecium, S. Enteritidis, E. coli,andP. aeruginosa). According to them,M. pulegium exhibited the best antibacterial activity compared toJ. phoenicea andC. longus. The MIC value ofM. pulegiumoil was <0.5 forE. faecium and 1 μL/mL forS. aureus, L. monocytogenes,E. coli, andS. enteritidis. Lawal et al. [124] have reported the antibacterial activity of essential oil ofOcimum gratissimum, O. kilimandscharicum,O. lamiifolium, andO. suave againstS. aureus, Bacillussp.,E. coli, P. aeruginosa, S. typhi, K. pneumoniae,andP. mirabilis. The MIC values varied between 1.25 and 10 mg/mL (flower oil) and between 0.16 and 10 mg/mL (leaf oil). The thyme oil obtained from leaves showed the presence of camphor, camphene, α-pinene, 1,8-cineole, borneol, and β-pinene, which exhibited effective antibacterial activity againstS. aureus, S. epidermidis, Streptococcussp., Pantoasp., andE. coli[53, 76]. The thyme oil showed MIC and MBC values of 627.7 μg/mL and 990.2 μg/mL, respectively, against theE. coli strain. The major compound thymol showed MIC and MBC values of 2786 μg/mL and 2540 μg/mL, respectively. Therefore, this study proposes the possible use of thyme oil as a potential antimicrobial agent for food preservation [76]. The oil obtained fromLaurus nobilis andLavandula intermediashowed inhibitory potential againstMycobacterium smegmatisandE. coli [37]. The bacterial strains (Shigella sonnei, Sarcina lutea,andMicrococcus flavus) were inhibited by the essential oil ofOriganum vulgare [54]. The zone of inhibition and MIC values ofO. vulgare oil were in the range of 9–36 mm and 125–600 μg/mL, respectively. Several food-borne pathogens such asBrochothrix thermosphacta, E. coli, Listeria innocua, L. monocytogenes, Pseudomonas putida, S. typhimurium,andShewanella putrefaciens were inhibited by some commercial essential oils including those ofOcimum basilicum,Petroselinum sativum, andRosmarinus officinalis [22]. The essential oil ofSyzygium cumini was found to contain α-pinene, β-pinene,trans-caryophyllene, 1,3,6-octatriene, delta-3-carene, α-caryophyllene, and limonene as major chemical compounds and possessed effective antibacterial activity against pathogenic bacterial strains such asE. coli, S. aureus, P. aeruginosa, Neisseria gonorrhoeae,B. subtilis, and S. aureus [73]. The essential oil exhibited moderate inhibition zones (12–14 mm) against the tested microbes. Andrade et al. [25] studied the antimicrobial activity of 27 different essential oils employed in aromatherapy procedures and found thatPiper nigrum, Melaleuca alternifolia, Copaifera officinalis,andCinnamomum cassiaessential oils were effective againstS. aureus andE. coli, whereasS. aromaticum essential oil was efficient againstP. aeruginosa strains. Khoury et al. [38] have reported thatJuniperus excelsa essential oil obtained from leaves and twigs was efficient at inhibitingS. aureus (MIC value of 64 mg/ml) andTrichophyton rubrum (MIC value of 128 mg/mL). Although the essential oil ofMentha suaveolens showed strong antibacterial activity againstS. xylosus with an MIC value of 14.4 μL/mL, it showed no activity against lactic acid bacterial strains exceptLactococcus lactis[41]. The essential oil of the herbStruchium sparganophora revealed the presence of β-caryophyllene, germacrene A, α-humulene, and germacrene D as major chemical constituents and it exhibited antibacterial activity againstS. typhi, B. cereus, B. subtilis, P. mirabilis,andP. aeruginosa[72]. The inhibitory zone for leaf oil ranged from 9.0±1.0 to 14.3±2.55 mm, whereas the essential oil from stem had inhibitory activity ranging from 18.5±2.2 to 20.0±0.0 mm.Daucus littoralis oil obtained from different parts of the plant has showed a strong antibacterial activity againstE. coliandS. aureus with an MIC value ranging from 20 to 40 μL/mL [31]. Likewise, Beatovic et al. [57] have reported the antibacterial activity ofOcimum basilicum oil againstS. typhimurium andE. coli. The MIC values ranged between 0.009 and 23.48 μg/mL, whereas the MBC values ranged from 0.28 to 135 μg/mL. In addition, essential oil of Australian-grownOcimum tenuiflorum (Tulsi) showed antibacterial activity against selected microbial pathogens including methicillin-resistantS. aureus(MRSA), E. coli,andP. aeruginosa with MIC values ranging from 2.25 to >4.5 μg/mL [125]. The essential oil ofPogostemon cablinwas shown to have effective antibacterial activity against many pathogenic bacterial strains includingE. coli, S. aureus, K. pneumoniae,andH. pylori [1, 60–64]. The GC-MS analysis of essential oils ofFoeniculum vulgare (Fennel) showed the occurrence oftrans-anethole, methylchavicol, limonene, and fenchone, whereasCuminum cyminum L. had γ-terpin-7-al, γ-terpinene, β-pinene, and cuminaldehyde as the major constituents. Both essential oils were effective againstS. typhimuriumandE. coli [28]. TheF. vulgare oil exhibited the lowest MIC values of 0.062 and 0.031% (v/v) againstE. coli andS. typhimurium, respectively, whereasC. cyminum oil showed MIC values of 0.250 and 0.125% (v/v) againstE. coli andS. typhimurium, respectively. The bacterial strainsS. aureus, B. cereus,andP. aeruginosawere strongly inhibited by the essential oil ofWarionia saharae,which contained β-eudesmol,trans-nerolidol, linalool, 1,8-cineole, camphor,p-cymene, and terpinen-4-ol as major compounds [79]. The MICs ranged between 0.039 and 0.156 mg/mL for all tested bacterial strains. The essential oil extracted from seeds ofTrachyspermum ammishowed activity against all 36 clinical isolates ofK. pneumoniae, E. coli,andS. aureusisolated from patients suffering from urinary tract infections [74]. An MIC value of 250 ppm was observed forK. pneumoniae, whereas it was observed to be 100 ppm forE. coli andS. aureus. The seed essential oils ofNigella sativa containing thymoquinone,p-cymene, α-thujene, thymohydroquinone, and longifolene as major phytocompounds were shown to exhibit strong antibacterial activity againstB.  cereus, E.  coli, P. aeruginosa, andS.  aureus. The oil was highly effective againstB. cereus, B. subtilis, andS. aureusand showed a complete zone of inhibition at 3000 ppm concentration. Moreover, the zones of inhibition forP. aeruginosa andE. coli were 20 and 25 mm, respectively [126]. A study by Cui et al. [69] has shown thatSalvia sclareaoil showed a considerable inhibitory potential against the growth ofE. coli, S. aureus, Bacillus pumilus, K. pneumoniae, B. subtilis, S. typhimurium,andP. aeruginosa with MIC and MBC of 0.05 and 0.1%, respectively. Ahmadi et al. [77] reported the antibacterial properties ofThymus kotschyanus essential oil againstB. cereus,E. coli, S. aureus, andS. epidermidis.The MIC values for these pathogens ranged from 0.097 to 6.25 μL/mL. The antibacterial activity ofEuphrasia rostkoviana essential oil againstE. faecalis,E. coli,K. pneumoniae,S. aureus,S. epidermidis, andP. aeruginosa was reported by Novy et al. [35]. In the study, all Gram-positive bacteria were effectively inhibited with an MIC of 512 μg/mL. The bacterial strainS. epidermidis was inhibited by the essential oils ofPlectranthus barbatus andP. amboinicus with an MIC value of 31 μg/mL [4, 33]. Likewise, the essential oil ofPlectranthus neochilus was shown to inhibit some cariogenic bacteria such asE. faecalis, S. salivarius, Streptococcus sobrinus, Streptococcus sanguinis, S. mitis, S. mutans,andLactobacillus casei[59]. The essential oil displayed moderate antibacterial activity againstE. faecalis(MIC=250μg/mL) andS. salivarius(MIC=250μg/mL). Meanwhile,S. sobrinus (MIC=62.5μg/mL),S. sanguinis (MIC=62.5μg/mL),S. mitis (MIC=31.25μg/mL), andLactobacillus casei (MIC=31.25μg/mL) were significantly inhibited. Interestingly, the MIC value forS. mutans was found to be 3.9 μg/mL. In another study, the essential oil ofFortunella margarita was shown to inhibitStreptococcus faecalis andP. aeruginosa significantly with inhibitory zones of 30 mm and 28 mm, respectively. In addition, moderate activity was observed forB. subtilis, S. aureus, Sarcina lutea,andE. coliwith inhibitory zones ranging from 20 to 25 mm [36]. Similarly,Achillea fragrantissima essential oil was effective againstS. aureus,S. epidermidis, andE. coli with the highest inhibition zone of 26 mm, 16 mm, and 16 mm, respectively [19]. In a study by Radaelli et al. [127], a major food-borne disease-causing agent,C. perfringens, was inhibited by essential oils of Brazilian MAPs such as basil, rosemary, marjoram, peppermint, thyme, andPimpinella anisum (anise). The MIC values were 1.25 mg/mL for thyme, 5.0 mg/mL for marjoram and basil, and 10 mg/mL for peppermint, rosemary, and anise. Mahmoud et al. [128] have shown the antimicrobial potential of 11 essential oils against all the tested microbes (S. aureus,E. coli, P. aeruginosa, andK. pneumoniae). Onion oil exhibited good antibacterial activity (MIC=12μg/mL) againstS. aureus. Chamomile (Anthemis nobilis) oil showed the best activity againstP. aeruginosa (MIC=5.1μg/mL). Origanum and chamomile oils showed the highest antibacterial activity (MIC7.2,7.5,and7.7μg/mL) againstE. coli.Origanum and ivy (Dolichos lablab) oils were effective againstK. pneumoniae with MIC values of 6.2 and 6.5 μg/mL, respectively. More recent studies have revealed that essential oils ofEucalyptus globulus, Matricaria chamomilla, Termitomyces schimperi,andR. officinalispossess antimicrobial activity againstS. aureus, S. pyogenes, S. typhi, Shigellaspp., E. coli,andP. aeruginosa[129]. The essential oil ofTermitomyces schimperi showed MIC values of <15.75 mg/mL for most of the tested bacteria, whereas other essential oils exhibited MIC values of 15.75–36.33 mg/mL against tested bacteria.


## 3.2. Antifungal Effects of Essential Oils

The essential oils and their constituents have been used against a broad range of fungal pathogens. Table2 summarizes various essential oils, their chemical compositions, and their antifungal activity against human pathogens. The essentials oils extracts from many plants such as basil, citrus, fennel, lemon grass, oregano, rosemary, and thyme have shown considerable antifungal activity against a wide range of fungal pathogens [65]. Arora and Kaur [120] observed the antimicrobial activity of essential oils extracted from spices against fungal pathogens. They found that garlic and clove extracts inhibited the growth ofCandida acutus, C. albicans, C. apicola, C. catenulata. C. inconspicua, C. tropicalis, Rhodotorula rubra, Saccharomyces cerevisiae,andTrigonopsis variabilis. Similarly, Grohs and Kunz [29] investigated mixtures of ground spices and demonstrated their efficacy against theC. lipolytica. According to the report of Ultee and Smid [55], oregano and thyme essential oils were some of the best inhibitors of fungal pathogens, because of the phenolic compounds (carvacrol and thymol) as main constituents, which disrupt fungal cell membranes. Likewise, Delaquis and Mazza [130] reported the antimicrobial effects of isothiocyanate isolated from the essential oils of onion and garlic plants. They stated that isothiocyanates may inactivate the extracellular enzymes through oxidative cleavage of disulfide bonds. Isothiocyanate was effective againstBotrytis, Fusarium, Penicillium, andCladosporium species. The antifungal activity of essential oils and their derivatives on the cell viability, mycelium growth, and mycotoxin-producing ability of molds has been studied [131]. It was concluded that, among all the tested essential oils, clove, cinnamon, and oregano essential oils were effective againstAspergillus parasiticus andFusarium moniliforme. The oil ofOriganum vulgare was efficient at inhibitingC. albicans,Aspergillus niger,Microsporum gypseum,Microsporum canis, Arthroderma cajetani, Trichophyton violaceum,Trichophyton mentagrophytes,Epidermophyton floccosum,T. rubrum, andTrichophyton tonsurans [52, 56]. The MIC values ranged from 0.625 to 10.0 mg/mL against all the tested microbes. The essential oils ofLippia sidoides,Rosmarinus officinalis,Salvia sclarea, andMomordica charantia were shown to inhibitC. albicans effectively [39, 44, 65]. Clove essential oil showed an MIC value of 0.125 and 0.062% (v/v) againstC. albicans andA. niger, respectively. Rosemary essential oil exhibited MIC values of 0.25 and 1.0% (v/v) againstC. albicans andA. niger, respectively [65]. Thymol and carvacrol effectively inhibitedC. albicans with inhibition zones of 10.6 and 9 mm, respectively [39].Similarly, Jirovetz et al. [70] analyzed the antifungal activity ofCoriandrum sativum oil againstCandida species. The essential oil obtained from leaves and flowers of theOcimumsp. showed considerable antifungal potential againstC. albicans, C. tropicalis, C. glabrata, Penicillium notatum, Rhizopus stolonifer, andMucor mucedo [27, 47, 48]. Likewise,Myrtus communis oil also inhibitedC. albicans, Aspergillus flavus, andFusarium culmorum [45, 85, 86]. The essential oils of thyme and clove completely inhibited the mycelial growth ofA. flavus when 3 μL of oil was added to the Petri-dish [86]. The MIC values ofM. communis oil were found to be 50 μL/mL forA. flavus and 30 μL/mL forA. ochraceus and F. culmorum [45]. In addition, Bouzabata et al. [87] analyzed the antifungal activity ofM. communis oil againstE. floccosum,Microsporum canis,Trichophyton rubrum(dermatophytes), andCryptococcus neoformans(yeast). An MIC value of 0.64 mg/mL was found to be lethal forM. canis,T. rubrum, andE. floccosum. However,Candida sp. andAspergillus sp. strains were relatively less inhibited, with MIC values of 1.25 mg/mL and 5 mg/mL, respectively. Tea tree oil(Melaleuca alternifolia) was effective against many fungal pathogens such asAlternariaspp.,A. flavus, A. fumigates, A. niger, Blastoschizomyces capitatus, C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, Cladosporiumspp.,Cryptococcus neoformans, E. floccosum, Fusariumspp., Malassezia furfur, Malassezia sympodialis, Microsporum canis, M. gypseum, Penicilliumspp.,Rhodotorula rubra, S. cerevisiae, T. mentagrophytes, T. rubrum, T. tonsurans,andTrichosporonsp. [81]. The essential oil ofSalvia sclarea, a medicinal plant, contained 56.88% linalyl acetate, 20.75% linalool, 5.08% germacrene D, and 3.41%  β-caryophyllene as the chief chemical compounds. The essential oil and the pure compounds (linalyl acetate and linalool) were shown to possess antifungal properties againstC. albicans, C. tropicalis, C. krusei, C. glabrata,andC. parapsilosis [84]. The antifungal activity ofPogostemon cablin oil againstAspergillus species andC. albicans has been reported by many authors [1, 90, 91]. MIC values of 0.064 mg/mL (cinnamon oil) and 0.032 mg/mL (pogostemon oil) forC. albicans, 0.129 mg/mL (cinnamon oil) and 0.064 mg/mL (pogostemon oil) forC. tropicalis, and 0.129 mg/mL (cinnamon oil) and 0.064 mg/mL (pogostemon oil) forC. krusei were observed [90]. The essential oils ofMentha pulegiumandM. suaveolens were efficient at inhibiting fungal species such asS. cerevisiae, Kloeckera apiculata, Candida zemplinina, Metschnikowia pulcherrima,andTetrapisispora phaffii [41]. The essential oil ofM. insularis showed the highest activity againstStaphylococcus xylosuswith an MIC value of 3.6 μL/mL. Moreover, Venturi et al. [82] reported the antifungal action of the essential oils extracted fromGlechon spathulata andG. marifolia against the dermatophytic fungiTrichophyton rubrum andEpidermophyton floccosum. The MIC values ranged from 10 to 83 mg/mL againstT. rubrum and 83 to 500 mg/mL againstE. floccosum. The essential oil ofDaucus littoralis was effective againstC. albicans with the MIC value ranging from 20 to 40 μL/mL [80]. Seed essential oil ofNigella sativa was shown to possess activity againstA.  flavus,F. moniliforme,Fusarium graminearum,andPenicillium viridicatum[46]. This oil was very effective and showed up to 90% zone inhibition againstF. moniliforme. Moreover, the dermatophytic fungusT. rubrum was repressed by the essential oil ofJ. excelsa and the MIC value was observed to be 128 mg/mL [38].More recently, eugenol (an essential oil compound from clove) was shown to cause permanent damage to the cells ofC. albicans and was considered to be an efficient antifungal agent. The MIC value of eugenol was found to be 1.0% v/v [92]. Beatovic et al. [57] have reported its antifungal potential againstOcimum basilicum,Aspergillus ochraceus, A. versicolor, A. niger, A. fumigates, Trichoderma viride,andP. funiculosum. Similarly, the inhibitory potential ofAegle marmelos oil againstC. albicans, A. niger,andF. oxysporumwas demonstrated. The essential oils extracted fromEremanthus erythropappus,P. barbatus,andP. amboinicus were shown to inhibit the growth ofC. albicans, Cryptococcus gattii, Cryptococcus neoformans, andS. cerevisiae [33]. Papajani et al. [88] have reported the antifungal activity of rosemary essential oil against dermatophytes such asA. cajetani,E. floccosum,M. gypseum,M. canis,T. violaceum,T. mentagrophytes,T. rubrum, andT. tonsurans and phytopathogens such asBotrytis cinerea andPleomorphomonas oryzae. According to them, concentration below 20 μg/mL was not effective and they suggested the use of concentrations above 100 μg/ml for better antifungal activity. The essential oil ofFortunella margarita exhibited activity againstA. nigerandC. albicans with a zone of inhibition of more than 30 mm [36]. In a recent study by Souza et al. [89], the essential oil ofPelargonium graveolens showed effective inhibitory potential againstC. tropicalis, a pathogen resistant to clinically used antifungal agents. The essential oil ofP. graveolens was found to be rich in geraniol and linalool. Four common essential oils of MAPs including litsea(Litsea cubeba), oregano, marjoram(Origanum majoranaL.), thymus, and their mixtures showed varied levels of antifungal activity againstC. albicans,C. tropicalis,C. krusei,C. guilliermondii,C. parapsilosis, andS. cerevisiae [132]. More recently, the essential oils obtained fromE. globulus, M. chamomilla, T. schimperi,andR. officinalis demonstrated effective antifungal activity againstTrichophytonspp.andAspergillusspp. [129].


## 3.3. Antiviral Effects of Essential Oils

Plant-based products and bioactive pure compounds may be a new source of antiviral drugs, as natural products have inherently high chemical diversity. Viral diseases are still a major problem for human health worldwide. So far, only a limited number of drugs are effective against many of these viruses, which has prompted research into finding new antiviral lead molecules. From our literature survey, it is evident that many essential oils possess antiviral properties against many DNA and RNA viruses, such as herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), dengue virus type 2, Junin virus, influenza virus adenovirus type 3, poliovirus, and coxsackievirus B1 [96, 105, 114, 133, 134].The antiviral activities of essential oils of major MAPs along with their constituents are detailed in Table3. The oregano and clove essential oils also exhibited strong antiviral activity against several nonenveloped RNA and DNA viruses such as adenovirus type 3, poliovirus, and coxsackievirus B1 [133, 134]. The replication capability of HSV-1 virus could be repressed by various essential oils under in vitro experimental conditions [135–137]. HSV-1 is the cause of common viral infections in humans, such as herpetic keratitis, herpetic encephalitis, mucocutaneous herpes infections, and neonatal herpes. Studies on the essential oils ofArtemisia arborescens, Glechon spathulata, andGlechon marifolia found that they strongly suppressed HSV-1 [82, 93, 138].Melissa officinalis essential oils have major constituents, namely, citral and citronellal, which could inhibit the replication of HSV-2 [96, 133, 137]. Likewise, the antiherpes activities of Australian tea tree oil, eucalyptus oil, and thyme oil have been previously reported [93, 135–138]. The major chemical constituent α-caryophyllene, which occurs in many essential oils of medicinal plants, is considered to be the best antiviral agent [135].Likewise, several phenylpropanoids and sesquiterpenes including eugenol, trans-anethole,β-eudesmol, β-caryophyllene, and farnesol, which are present in essential oils, also have antiviral properties against HSV [135]. Similarly, another major compound of essential oils, eugenol, showed virucidal activity against human herpesvirus [137, 139]. Some triterpenes and sesquiterpenes also possess antiviral activity against different herpesviruses and rhinovirus [140–143]. García et al. [144] reported the antiviral activity ofArtemisia douglasiana andEupatorium patens essential oils against the dengue virus. In addition,Lippia junellianaandLippia turbinate essential oils showed activity against the Junin virus. Anti-influenza A (H2N2) activity was exhibited by the essential oil compounds ofPogostemon cablin [1, 97–99] and the antiviral property of the essential oils obtained from fruits and leaves ofFortunella margarita exhibited potential activity against avian influenza A virus (H5N1) [94]. Roy et al. [100] indicated the potential antiviral activity ofTrachyspermum ammi oil against Japanese encephalitis virus (JEV). Similarly, Zeedan et al. [19] reported the antiviral activity ofAchillea fragrantissima against the ORF virus (a parapox virus). More recently, Pourghanbari et al. [145] evaluated in vitro antiviral activity ofM. officinalis (lemon balm) essential oil and oseltamivir and their synergistic effect on avian influenza virus (AIV) subtype H9N2. They found that various concentrations of lemon balm essential oil suppressed influenza virus replication. However, it had improved efficacy when coadministered with the antiviral agent oseltamivir. Essential oils obtained from Colombian MAPs such asLepechinia salviifolia,Minthostachys mollis,Hyptis mutabilis,Lepechinia vulcanicola, andOcimum campechianum were reported to possess antiviral activity against human herpes viruses types 1 and 2 [95]. They also reported that these essential oils inhibit viral activity during their early stages of infection. Thus, plant-based essential oils could be used as antiviral agents against several viral diseases in humans and have the potential to be used as alternatives to synthetic antiviral drugs.


## 4. Mechanism of Antimicrobial Action of Essential Oils against Human Pathogens

MAPs contain several types of chemical constituents that have antimicrobial properties. These are synthesized to protect the plants from microbial pathogens. The antimicrobial properties of essential oils mainly depend on their chemical constituents and the quantity of the major single compounds [15]. These chemical compounds are secreted through a series of molecular interactions under specific biotic/abiotic stress conditions [15, 146]. Each compound may exhibit a different mechanism of action against microbes. Overall, the mechanism of antibacterial action is mediated by a series of biochemical reactions in the bacterial cell, which are dependent on the type of chemical constituents present in the essential oil [15, 110]. Moreover, the antibacterial activity of essential oils also differs because of different bacterial architecture, such as Gram-positive and Gram-negative bacteria, which differ in their cell membrane compositions [83, 114]. In the following sections, the mechanism of antimicrobial activities of essential oils is described with reference to the available literature. The possible antimicrobial actions of essential oils are illustrated in Figure 2.Figure 2
Antimicrobial mechanisms of essential oils on microbes.


### 4.1. Action against Bacterial Pathogens

Various mechanisms of antibacterial activity of essential oils have been proposed. Essential oils primarily destabilize the cellular architecture, leading to the breakdown of membrane integrity and increased permeability, which disrupts many cellular activities, including energy production (membrane-coupled), membrane transport, and other metabolic regulatory functions. The disruption of the cell membrane by essential oils may assist various vital processes such as energy conversion processes, nutrient processing, the synthesis of structural macromolecules, and the secretion of growth regulators [66]. The essential oils may affect both the external envelope of the cell and the cytoplasm [15, 114]. Owing to their lipophilic nature, essential oils are easily penetrable through the bacterial cell membranes. Essential oils of various MAPs were reported to cause increased bacterial cell membrane permeability leading to the leakage of cellular components and loss of ions [66, 114, 147]. The antibacterial effect of essential oils is also linked to reduced membrane potentials, the disruption of proton pumps, and the depletion of the ATP [148]. This alteration in the cell organization may cause a cascade effect, resulting in other cell organelles being affected [43]. Likewise, Cox et al. [149, 150] have demonstrated that tea tree oil inhibits the growth ofS. aureus andE. coli by altering cell permeability, increasing the leakage of intracellular K+ ions and disturbing cell respiration. The essential oils pass through the cell wall and cytoplasmic membrane, which may disrupt the arrangement of dissimilar fatty acids, phospholipids bilayers, and polysaccharides molecules [114, 147, 151]. All these events may be responsible for the coagulation of inner cellular components in the cytoplasm and break down of the bonds between the lipid and protein layers [110].In some cases, the pure compounds of essential oils exhibit higher antibacterial activity compared to the essential oil. The antibacterial effect of essential oil constituents such as thymol, menthol, and linalyl acetate is because of a perturbation of the lipid fractions of bacterial plasma membranes [152]. This may affect the permeability of the membrane and induce leakage of intracellular materials. Carvacrol is a hydrophobic compound that influences cell membranes by altering the composition of fatty acids, which then affects the membrane fluidity and permeability [16]. However, its exact mechanism of action is still unclear. It was reported that carvacrol significantly depleted the internal ATP pool of bacterial cells [16, 153]. In another study, carvacrol induced the leakage and loss of ATP from bacterial cells [154]. Likewise, the compounds methyl carvacrol, menthol, citronellol, and thymol also cause an enlargement of the cell membrane that leads to passive diffusion of ions between the expanded phospholipids [16, 147, 153, 154]. Another effect of essential oils on cell membranes is the inhibition of toxin secretion. Ultee and Smid [55] reported that exposure ofB. cereusto carvacrol resulted in the inhibition of toxin production, and application of oregano essential oil completely abolished the enterotoxin production ofS. aureus.Thus, the secretion of toxins may be prevented by modifications in the bacterial membrane due to the influence of the essential oil compounds on the trans-membrane transport process in the plasma membrane, which limits the release of toxins to the external environment [155]. Another mechanism of action is bytrans-cinnamaldehyde, which enters the periplasm of the cell and disrupts cellular functions [16, 156]. Moreover,p-cymene has a greater affinity towards bacterial cell membranes and thus may disturb the membrane integrity [16, 157]. The outer membrane proteins are also affected by essential oil components. For example, carvacrol can disturb the insertion and folding of proteins such as DnaK and GroEL [16, 110]. Carvacrol can also inhibit the synthesis of flagellin, a microbial protein required for bacterial motility [16]. The phenylpropene, eugenol, also exhibits activity by modifying the fatty acid outline to alter the cytoplasmic membrane of different bacteria. In addition, it can destroy various bacterial enzymes such as ATPase, amylase, histidine carboxylase, and proteases [158, 159]. Likewise, cinnamaldehyde was reported to inhibit ATPase enzymes and disrupt the outer cell membrane [160]. Other studies have found that vanillin exhibited antimicrobial activity by obstructing the pathways of bacterial respiration and disrupting the flux of K+ ions and pH gradient [161]. Similarly, carveol, citronellal, and carvone essential oils were shown to modify hydrophobicity and disrupt membrane integrity, leading to the leakage of K+ions [162]. Some essential oils can inhibit the cell-cell communication quorum sensing network mediated by various bacterial signal molecules [163]. The efficacy of the antibacterial effect of essential oils or their individual compounds may differ from one microbe to another. Hence, elucidation on the exact mechanisms of action of each essential oil and their components is required, including further study on the numerous microbial strains/species. Furthermore, detailed study on the components of essential oils would be helpful to improve our understanding of their mechanism of antimicrobial activity.


### 4.2. Action against the Fungal Pathogens

The antifungal actions of essential oils are similar to that of previously explained antibacterial mechanisms. Generally, exposure of essential oils leads to the coagulation of the cellular components because of irreversible cell membrane damage. In yeast cells, essential oils establish a membrane potential across the cell membrane and disrupt the production of ATP, which leads to cell membrane damage [85]. The essential oils have the ability to penetrate and disrupt the fungal cell wall and cytoplasmic membranes through a permeabilization process, which leads to the disintegration of mitochondrial membranes. This is caused by alterations in the flow of electrons inside the electron transport system (ETS) pathway. This may also damage the lipids, proteins, and nucleic acid contents of cells infected by the fungal pathogens [164]. The essential oils could also disrupt the depolarization of the mitochondrial membranes by affecting ions channels, especially Ca2+ions, proton pumps, and ATP pools, and therefore decrease the membrane potential. This change in the fluidity of membranes may cause electrolyte leakage and hinder cytochrome C pathways, proteins metabolism, and calcium ion concentrations. Therefore, the permeabilization of inner and outer mitochondrial membranes may result in the cell apoptosis or necrosis leading to cell death [165].


### 4.3. Actions against the Viruses

At present, various essential oils may be a promising alternative against viral infections [105]. However, the detailed understanding on the antiviral action of essential oils still requires more research. Some of the reported mechanisms of action of essential oils are reported in this section. Essential oils might interfere with virion envelopment, designed for entry into host cells. For instance, the sesquiterpene triptofordin C-2 was reported to suppress the synthesis of viral proteins and inhibit the early gene expression process of the HSV-1 virus [141]. Schnitzler et al. [135] investigated the antiviral activity of star anise essential oil as well as compounds such as eugenol,trans-anethole, farnesol, β-eudesmol, β-caryophyllene, and β-caryophyllene oxide against HSV-1. They found the direct inactivation of HSV-1 particles, which is also reported in another study where eugenol was used [141]. Moreover, eugenol directly inactivates the growth of the herpes virus [139], whereas isoborneol (monoterpene) affected the glycosylation process of viral proteins, which inhibited the growth of HSV-1 [166]. Similarly, essential oils of ginger, thyme, hyssop, and sandalwood were able to inhibit acyclovir-resistant HSV-1 [136]. Possible mechanisms of action include the inhibition of virus replication by hindering cellular DNA polymerase and alteration in phenylpropanoid pathways. Furthermore, sesquiterpenes are known to inhibit cytomegalovirus (CMV) early gene expression [142]. According to Pourghanbari et al. [145], the essential oil of lemon balm inhibits influenza virus replication at different replication cycles by directly interacting with the virus particles.


## 4.1. Action against Bacterial Pathogens

Various mechanisms of antibacterial activity of essential oils have been proposed. Essential oils primarily destabilize the cellular architecture, leading to the breakdown of membrane integrity and increased permeability, which disrupts many cellular activities, including energy production (membrane-coupled), membrane transport, and other metabolic regulatory functions. The disruption of the cell membrane by essential oils may assist various vital processes such as energy conversion processes, nutrient processing, the synthesis of structural macromolecules, and the secretion of growth regulators [66]. The essential oils may affect both the external envelope of the cell and the cytoplasm [15, 114]. Owing to their lipophilic nature, essential oils are easily penetrable through the bacterial cell membranes. Essential oils of various MAPs were reported to cause increased bacterial cell membrane permeability leading to the leakage of cellular components and loss of ions [66, 114, 147]. The antibacterial effect of essential oils is also linked to reduced membrane potentials, the disruption of proton pumps, and the depletion of the ATP [148]. This alteration in the cell organization may cause a cascade effect, resulting in other cell organelles being affected [43]. Likewise, Cox et al. [149, 150] have demonstrated that tea tree oil inhibits the growth ofS. aureus andE. coli by altering cell permeability, increasing the leakage of intracellular K+ ions and disturbing cell respiration. The essential oils pass through the cell wall and cytoplasmic membrane, which may disrupt the arrangement of dissimilar fatty acids, phospholipids bilayers, and polysaccharides molecules [114, 147, 151]. All these events may be responsible for the coagulation of inner cellular components in the cytoplasm and break down of the bonds between the lipid and protein layers [110].In some cases, the pure compounds of essential oils exhibit higher antibacterial activity compared to the essential oil. The antibacterial effect of essential oil constituents such as thymol, menthol, and linalyl acetate is because of a perturbation of the lipid fractions of bacterial plasma membranes [152]. This may affect the permeability of the membrane and induce leakage of intracellular materials. Carvacrol is a hydrophobic compound that influences cell membranes by altering the composition of fatty acids, which then affects the membrane fluidity and permeability [16]. However, its exact mechanism of action is still unclear. It was reported that carvacrol significantly depleted the internal ATP pool of bacterial cells [16, 153]. In another study, carvacrol induced the leakage and loss of ATP from bacterial cells [154]. Likewise, the compounds methyl carvacrol, menthol, citronellol, and thymol also cause an enlargement of the cell membrane that leads to passive diffusion of ions between the expanded phospholipids [16, 147, 153, 154]. Another effect of essential oils on cell membranes is the inhibition of toxin secretion. Ultee and Smid [55] reported that exposure ofB. cereusto carvacrol resulted in the inhibition of toxin production, and application of oregano essential oil completely abolished the enterotoxin production ofS. aureus.Thus, the secretion of toxins may be prevented by modifications in the bacterial membrane due to the influence of the essential oil compounds on the trans-membrane transport process in the plasma membrane, which limits the release of toxins to the external environment [155]. Another mechanism of action is bytrans-cinnamaldehyde, which enters the periplasm of the cell and disrupts cellular functions [16, 156]. Moreover,p-cymene has a greater affinity towards bacterial cell membranes and thus may disturb the membrane integrity [16, 157]. The outer membrane proteins are also affected by essential oil components. For example, carvacrol can disturb the insertion and folding of proteins such as DnaK and GroEL [16, 110]. Carvacrol can also inhibit the synthesis of flagellin, a microbial protein required for bacterial motility [16]. The phenylpropene, eugenol, also exhibits activity by modifying the fatty acid outline to alter the cytoplasmic membrane of different bacteria. In addition, it can destroy various bacterial enzymes such as ATPase, amylase, histidine carboxylase, and proteases [158, 159]. Likewise, cinnamaldehyde was reported to inhibit ATPase enzymes and disrupt the outer cell membrane [160]. Other studies have found that vanillin exhibited antimicrobial activity by obstructing the pathways of bacterial respiration and disrupting the flux of K+ ions and pH gradient [161]. Similarly, carveol, citronellal, and carvone essential oils were shown to modify hydrophobicity and disrupt membrane integrity, leading to the leakage of K+ions [162]. Some essential oils can inhibit the cell-cell communication quorum sensing network mediated by various bacterial signal molecules [163]. The efficacy of the antibacterial effect of essential oils or their individual compounds may differ from one microbe to another. Hence, elucidation on the exact mechanisms of action of each essential oil and their components is required, including further study on the numerous microbial strains/species. Furthermore, detailed study on the components of essential oils would be helpful to improve our understanding of their mechanism of antimicrobial activity.


## 4.2. Action against the Fungal Pathogens

The antifungal actions of essential oils are similar to that of previously explained antibacterial mechanisms. Generally, exposure of essential oils leads to the coagulation of the cellular components because of irreversible cell membrane damage. In yeast cells, essential oils establish a membrane potential across the cell membrane and disrupt the production of ATP, which leads to cell membrane damage [85]. The essential oils have the ability to penetrate and disrupt the fungal cell wall and cytoplasmic membranes through a permeabilization process, which leads to the disintegration of mitochondrial membranes. This is caused by alterations in the flow of electrons inside the electron transport system (ETS) pathway. This may also damage the lipids, proteins, and nucleic acid contents of cells infected by the fungal pathogens [164]. The essential oils could also disrupt the depolarization of the mitochondrial membranes by affecting ions channels, especially Ca2+ions, proton pumps, and ATP pools, and therefore decrease the membrane potential. This change in the fluidity of membranes may cause electrolyte leakage and hinder cytochrome C pathways, proteins metabolism, and calcium ion concentrations. Therefore, the permeabilization of inner and outer mitochondrial membranes may result in the cell apoptosis or necrosis leading to cell death [165].


## 4.3. Actions against the Viruses

At present, various essential oils may be a promising alternative against viral infections [105]. However, the detailed understanding on the antiviral action of essential oils still requires more research. Some of the reported mechanisms of action of essential oils are reported in this section. Essential oils might interfere with virion envelopment, designed for entry into host cells. For instance, the sesquiterpene triptofordin C-2 was reported to suppress the synthesis of viral proteins and inhibit the early gene expression process of the HSV-1 virus [141]. Schnitzler et al. [135] investigated the antiviral activity of star anise essential oil as well as compounds such as eugenol,trans-anethole, farnesol, β-eudesmol, β-caryophyllene, and β-caryophyllene oxide against HSV-1. They found the direct inactivation of HSV-1 particles, which is also reported in another study where eugenol was used [141]. Moreover, eugenol directly inactivates the growth of the herpes virus [139], whereas isoborneol (monoterpene) affected the glycosylation process of viral proteins, which inhibited the growth of HSV-1 [166]. Similarly, essential oils of ginger, thyme, hyssop, and sandalwood were able to inhibit acyclovir-resistant HSV-1 [136]. Possible mechanisms of action include the inhibition of virus replication by hindering cellular DNA polymerase and alteration in phenylpropanoid pathways. Furthermore, sesquiterpenes are known to inhibit cytomegalovirus (CMV) early gene expression [142]. According to Pourghanbari et al. [145], the essential oil of lemon balm inhibits influenza virus replication at different replication cycles by directly interacting with the virus particles.


## 5. Conclusion and Future Prospects

The essential oils extracted from various MAPs possess strong antimicrobial activity against various bacterial, fungal, and viral pathogens. The reactivity of essential oils depends upon the nature of their functional groups and orientation. Essential oils are considered to be potent against a diverse range of pathogens. Essential oils may disrupt the cell membrane of the targeted pathogens by increasing membrane permeability, inducing leakage of vital intracellular constituents, and interrupting the cellular metabolism and enzyme kinetics of the targeted pathogens. The present study reveals more information on in vitro research studies of essential oils; however, more efforts are required to conduct clinical trials in the future. Most of these antimicrobial studies using essential oils have failed to provide definite information on their chemical nature as well as their mechanisms of action. This poses ambiguity on the reproducibility and accuracy of their discoveries. Therefore, further research should focus on exploring the molecular mechanisms of essential oils and their individual chemical compounds. Biopharmaceutical industries are in need of ecofriendly alternative drug molecules to treat diseases associated with microbial pathogens and body metabolism. Thus, essential oils of MAPs might be a prospective source of alternative antimicrobial agents and may play an important role in the discovery of new drugs for the treatment of a wide range of pathogenic microorganisms in the near future.



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*Source: 3012462-2016-12-20.xml*