Essential oils are complex mixtures of hydrocarbons and their oxygenated derivatives arising from two different isoprenoid pathways. Essential oils are produced by glandular trichomes and other secretory structures, specialized secretory tissues mainly diffused onto the surface of plant organs, particularly flowers and leaves, thus exerting a pivotal ecological role in plant. In addition, essential oils have been used, since ancient times, in many different traditional healing systems all over the world, because of their biological activities. Many preclinical studies have documented antimicrobial, antioxidant, anti-inflammatory and anticancer activities of essential oils in a number of cell and animal models, also elucidating their mechanism of action and pharmacological targets, though the paucity of in human studies limits the potential of essential oils as effective and safe phytotherapeutic agents. More well-designed clinical trials are needed in order to ascertain the real efficacy and safety of these plant products. In evolutionary terms, plant secondary metabolism greatly contributed to the colonization of terrestrial environments by plant organisms. Indeed, in an ecological context, secondary metabolites relate plants to their ecosystem. Pigments and aromatic compounds confer colour and scent to reproductive organs and fruits, thus attracting pollinators and favouring seed dispersal by animals. However, volatile compounds can also repel phytophagous organisms, including virus and phytoplasma vectors, whereas phytoalexins are broad-spectrum antimicrobial metabolites .In this complex scenario, humans have greatly benefited from plants and their secondary metabolites. During the plant-human coevolution, plants represented (and represent) a nearly unlimited source of food, feed for domesticated animals, fibres for clothes and, not the least, medicaments. Among the vastness of plant products, essential oils deserve particular attention. These are complex mixtures of hydrocarbons and oxygenated hydrocarbons arising from the isoprenoid pathways, mainly consisting in monoterpenes and sesquiterpenes. Essential oils are produced and secreted by glandular trichomes, specialized secretory tissues diffused onto the surface of plant organs, particularly flowers and leaves .This review deals with essential oils from both the plants’ and humans’ perspective, focusing on their pivotal role in plant chemoecology and as source of bioactive phytochemicals and phytotherapeutics for humans. Special emphasis will be put on the uses of essential oils in different traditional healing systems worldwide. Mechanisms of action, and molecular and biochemical targets of essential oils both in prokaryotic and eukaryotic cells will be reviewed, as well as the preclinical and clinical evidences of their efficacy.A long-standing discussion in plant physiology is whether the so-called secondary metabolites (henceforth SMs) are just waste products or they have a role in increasing plant fitness. The co-evolutionary hypothesis, as presented by Fraenkel, Erlich and others since the 1960s ,4 proposOne particular group of SMs is the volatile ones, comprising mainly terpenoids, but also phenylpropanoids, polyketides and nitrogen- and sulfur-containing compounds. Although to describe this heterogeneous group of compounds the term “essential oils” has been used, this actually defines the molecules extracted from the plants , while t2 levels and ozone levels, and biotic factors such as competitors (both interspecific and intraspecific), microbial pathogens, herbivores and other harmful insects, and beneficial animals such as pollinators and seed dispersers [PVs are supposed to mediate the relationship of a plant with abiotic factors such as light, temperature, draught, COspersers ,15,16. HThe chemical defense responses can be described as constitutive or inducible, and as direct or indirect . ConstitConstitutive PVs act on herbivores mainly by directly repelling them and/or by inhibiting their feeding. They also act against microbial pathogens by inhibiting their growth via direct antibacterial, antiviral and antifungal activities, and also by repelling viral vectors  .Inducible PVs are activated by pathogen or herbivore attacks . They haMore specifically herbivore attack and feeding cause the release of defense signals and defense responses . After an herbivore attack, there is an extensive gene expression rearrangement in the attacked plant that seems to be at the origin of HIPVs synthesis . WoundinSecreted HIPVs comprise mono- and sesquiterpenes, but also specialized groups of molecules such as green leaf volatiles (henceforth GLVs) and phytohormones such as ethylene, methyl salicylate, jasmonic acid, and others ,15,16.6 reactive electrophile species, comprising aldehydes such as (Z)-3-hexenal and n-hexenal, alcohols such as (Z)-3-hexenol, and esters such as (Z)-3-hexen-1-yl acetate and its E-isomers. They derive from cellular membrane C18 fatty acids, which are cleaved by LOX/lyase enzymes to give C12 and volatile C6 GLVs, which are released in a matter of minutes after the attack [GLVs are Ce attack ,13. Theye attack , modulatAn ideal chronology of plants’ responses to an attack could be thus described: (i) herbivore attack: immediate release of constitutively synthesized PVs upon rupture of storage structures such as glandular trichomes; (ii) from few seconds to few minutes after the attack, wounding causes the release of de novo synthesized, induced PVs (HIPVs) such as GLVs and terpenoids; (iii) continuous damage, oral secretions, oviposition fluids, infection or HIPVs signaling: release, after 12–24 h, usually for the next photoperiod, of induced phytohormones like jasmonic acid, salicylic acid, ethylene, and de novo synthesis of terpenoids and shikimate derivatives.Salvia leucophylla Greene is an exemplary case of allelopathy and of the role played by monoterpenes  as inhibitors of seed germination and of competition. A revision of the exact modality of Salvia PVs release has been proposed by Sakai and Yoshimura [oshimura : volatil2 and ozone levels. Isoprene and monoterpenes increase general thermal tolerance of photosynthesis, protect photosynthetic apparatus and help it to maintain photosynthetic activity under high temperature stress (temperatures above 40 °C) by stabilizing the thylakoid membranes and quenching ROS [PVs synthesis is affected by temperature, light, draught, COhing ROS .Z)-3-hexenyl acetate, but also constitutive PVs, can travel from a herbivore-damaged part to an undamaged one, leading to better protection of the latter, probably via activation of defense genes, priming of the tissues and consequent more vigorous response after a real attack. Since plants have a limited vascular connection, and even when it exists, phloem-mediated signaling is slow; HIPVs can be used instead to prime other parts of the plant for a possible attack [HIPVs, especially (e attack .Plants (both conspecific and heterospecific) exposed to HIPVs show increased transcription of defense-related genes and altered levels of defense-related metabolites . HIPVs aDirect defense responses comprise PVs that are toxic and repellent; in addition, they can be antinutritional agents and reduce digestibility, growth and reproduction . They taIndirect defense responses are normally inducible (HIPVs) and comprise volatile compounds that attract, nourish or otherwise favor another organism that reduces herbivore pressure . HIPVs rGlandular trichomes (GTs) are modified epidermal hairs containing cells specialized for PVs synthesis and secretion . NoteworGTs is usually not connected to the vascular system , but devThey are generally divided in two large subgroups, peltate and capitate GTs. Capitate GTs usually has one basal cell, one to many stalk cells and one to a few apical cells. They usually secrete non- or poorly-volatile SMs stored in a large SCS . PeltateThe GTs cells differ from normal plant cells in that they have a very dense cytoplasm with nucleus and nucleolus, no large central vacuole, extensive endoplasmic reticulum (ER), many plastids (amoeboid leucoplasts), relatively few Golgi bodies, abundant mitochondria and numerous plasmodesmata .There are two main pathways for terpene biosynthesis, and most researchers hold that all steps of this route take place in the secretory cells themselves  Figure :Mevalonic acid (MVA) pathway operates in the cytosol, but sub-cellular details are lacking, perhaps there is an involvement of endoplasmic reticulum (ER) and peroxisomes. It synthesizes sesquiterpene precursors  .d-erythrytol 4-phosphate (MEP) pathway are located in the plastids. It synthesizes only monoterpene precursors . Although MEP is plastid-located, the enzymes necessary for sesquiterpene synthesis are cytosolic. Hence, MEP-derived intermediates isopentenyl pyrophosphate (IPP) or dimethylallyl pyrophosphate (DMAPP) need to travel from plastids to cytosol. It has been suggested that MEP dominates terpenoid production [All the enzymes of the other route, the 2C-methyl-oduction .The intracellular compartmentalization of terpene biosynthesis is still unclear. It has been observed that at secretory stage GTs show highly developed smooth endoplasmic reticulum (SER), amoeboid leucoplasts, sometimes surrounded by periplastic SER, with many plastid-SER membrane contacts. These plastids showed the greatest changes during development and in relations to secretions , correlaThe close association, in secreting peltate GTs, of plastids, SER (whose surface serves as the location of terpene enzymes) and plasma membrane, the common presence of membrane contact sites (MCSs) between ER and leucoplasts, ER and plasma membrane, and ER and mitochondria suggests that plastids (and maybe SER) have an important role in monoterpene biosynthesis .Mentha x piperita, ER, mitochondria and cytosol may be all involved: beginning with the synthesis of (−)-limonene from IPP and DMAPP in leucoplasts, its hydroxylation to (−)-trans-isopiperitenol in SER, its conversion to (−)-trans-isopiperitenone in mitochondria, and a final creation of many metabolites in cytosol [In fact, IPP and DMAPP seem to originate in the plastids from the MEP pathway, while the stroma of leucoplasts contains the enzymes for the first steps of monoterpene biosynthesis (with or without the involvement of rough ER) . As show cytosol . The nex cytosol ,23.The primary function of GTs (in particular in the Lamiaceae) is related to defense responses, both constitutive and inducible, against herbivores and pathogens , and it They can reduce insect movement, protect beneficial phylloplane organisms, deter insects and herbivores, immobilize them, inhibit fungal and bacterial attacks, and mediate allelopathy .GTs can also act, in some species, as detection sensors. The disruption of GTs by walking insects can induce a defensive readiness that allows plants to respond more quickly. It triggers release of JA, JA signaling and induction of defense genes within 3–24 h. Thus, any plant can be primed by walking, exploring or ovipositioning insects to a state of intermediate alarm. Although this priming is non-selective , it is energetically advantageous because it allows an intermediate (less expensive) step between no alarm and full-fledged alarm .In certain cases, SMs in GTs can be transported via the stalk to distal plant tissues to protect them, as in the case of pyrethrins produced in fruit GTs that are transferred to the seeds which, being hairless, cannot secrete their own chemical defenses .They also have non-defensive roles, such as temperature regulation, light reflectance, decreased water loss (via light reflection), reduced mechanical abrasion, reduced leaf humidity, reduced photosynthesis (via light reflection), attraction of pollinators and seed dispersal .Essential oils are a complex mixture of molecules, which generally contains more than 20 different components of low molecular weight with very variable concentrations. In general, monoterpenes and sesquiterpenes are the main components of essential oils, though diterpenes and phenylpropanoids can be present to a different extent. Many of these molecules are found in low concentrations, while few of them are the main components that can represent up to 70% of total oil and will be the main responsible for the biological effects of the oil ,30. UntiThe cytotoxic properties of essential oils result from the complex interaction between the different classes of compounds such as phenols, aldehydes, ketones, alcohols, esters, ethers or hydrocarbons ,32,33. IThymus and Origanum, Ocimum basilicum L. and Cinnamomum zeylanicum Breyne are mainly associated to the presence of thymol, carvacrol, eugenol and cinnamaldehyde, respectively [Plants produce a wide variety of secondary metabolites many of which play a role in plant protection against predators and microbes potentially pathogenic derived from their cytotoxic properties or reduced palatability against herbivores. In addition, the increasingly selection of bacteria resistant to many antibiotics has led to research into the use of essential oils as potential alternatives. The presence of components with phenolic structures or aldehydes, such as thymol, carvacrol, eugenol, cinnamaldehyde and citral, were greatly active against microorganisms ,37. Thesectively ,40,41. HN-phenyl-l-napthylamine indicates that formation of unregulated pores in the membrane and an increased probability of cell death. Finally, cell-to-cell communication among bacteria (quorum sensing), used to control group behaviors, including virulence factor production or biofilm formation, is another central target that could help to reduce antimicrobial resistance [The cytotoxic effects of essential oils are primarily made through disrupting the structure of membranes, leading to bacterial cell permeabilization. As a result of membrane permeabilization, all other cellular functions including membrane potential, efflux pump activity or respiratory activity are also compromised ,42,43. Msistance .Forsythia koreana Nakai induced changes in cell wall morphology, cell wall lysis, and pore formation of Escherichia coli and Listeria monocytogenes [Pimenta pseudocaryophyllus (Gomes) Landrum against the main bacteria responsible for bad perspiration odor (Staphylococcus epidermidis or Proteus hauseri) and Cinnamomum longepaniculatum (Gamble) N. Chao ex H. W. Li leaf essential oil against Staphylococcus aureus, E. coli and Salmonella enteritidis [Melaleuca alternifolia L. (tea tree) disrupted the permeability barrier of E. coli and S. aureus membranes leading to the loss of chemiosmotic control [E. coli, but also inhibited the respiration and increased the permeability of bacterial membranes as determined by uptake of propidium iodide. Origanum compactum Benth (oregano) and Cinnamomum verum J. Presl. essential oils caused potassium leakage and uptake of propidium iodide in both Pseudomonas aeruginosa and S. aureus associated with loss of membrane permeability and structural alterations [Ginkgo biloba L. leaf essential oil was also investigated against foodborne pathogenic bacteria [G. biloba oil induced considerable morphological alterations on the cell wall of diverse foodborne pathogenic bacteria which was also related to release of extracellular ATP, increase of 260 nm-absorbing materials and leakage of potassium ions. The essential oil from edible seaweed, Enteromorpha linza (L.) J. Agardh, was also highly active against the foodborne pathogenic bacteria Bacillus cereus and S. aureus, inducing significant increase in leakage of 260 nm-absorbing materials and potassium ions from the cell membrane and loss of high salt tolerance [Thymus daenensis Čelak. formulated as a water-dispersible nanoemulsion in order to facilitate the access of the essential oil into the bacterial cell [Citrus sinensis (L.) Osbeck.) and bergamot (Citrus bergamia Risso & Poit.) (1:1 v/v) was tested against Enterococcus faecium and Enterococcus faecalis [N-phenyl-1-naphthylamine. Moreover, a decrease in intracellular pH, in membrane potential and a reduced ATP synthesis were also reported. Essential oils from Satureja hortensis L. and Salvia fruticosa Mill. altered the outer membrane permeability of Fusobacterium nucleatum, key bacteria in oral biofilms [N-phenyl-1-naphthylamine uptake, was significantly increased by the treatment with both essential oils. The treatment of E. coli and L. monocytogenes with Spanish oregano (Coridothymus capitatus Rchb. f.), Chinese cinnamon (Cinnamomum cassia (L.) D. Don.), and savory (Satureja montana L.) essential oils induced the depletion of the intracellular ATP concentration, reduced intracellular pH, and evident damage to cell membranes [Diverse studies reported the capability of essential oils to alter the membrane structure and permeability observed with electron microscopy and, in most of cases, also evidenced by the release of diverse elements outside the cell. Lemongrass essential oil caused discernible cell membrane alterations and formed electron-dense inclusions detected with electron microscopy to planktonic and sessile growth of a sulfate reducing bacterium . The leaytogenes . In thiseritidis ,50. The  control . The treerations ,53. Ginkbacteria . The resolerance . An inteial cell . The nanfaecalis . The resbiofilms . Membranembranes .Chromobacterium violaceum and P. aeruginosa [C. violaceum and swarming motility in P. aeruginosa, followed by cinnamon, lavender, and peppermint oils. A similar study performed by Szabó et al. [C. violaceum as sensor strain evidenced that rose, geranium, lavender and rosemary oils were highly potent quorum sensing inhibitors. On the other hand, eucalyptus and citrus oils reported moderate effects, and chamomile, orange and juniper oils were ineffective. The oregano essential oil has been also reported to exert inhibitory quorum sensing activity using C. violaceum as bacterial model [P. aeruginosa and Aeromonas hydrophila, indicating a broad-spectrum of activities [Origanum heracleoticum L.) also inhibited the expression of virulence-associated genes in enterohaemorrhagic strain of E. coli [P. aeruginosa when treated with ferula oil (Ferula asafetida H.Karst), whereas pyoverdine and elastase production, but not pyocyanin and biofilm production were decreased after dorema (Dorema aucheri Boiss.) treatment [The effects of essential oils were also investigated against quorum sensing. An interesting work investigated the inhibitory effects of 21 essential oils against quorum sensing in ruginosa . Clove oó et al.  using thal model . Peppermtivities . Moreove E. coli . In anotreatment .E. coli strain that cinnamon bark essential oil as well as lavender essential oil induced irreversible membrane damage and also inhibited quorum sensing evidenced by reduced production of bioluminescence [Cistus ladaniferus Gouan ex Steud essential oil, which was mainly constituted by mono- and sesquiterpene alcohols, induced cell wall distortion with an outer cytoplasmic membrane detachment in a multidrug resistant strain of Enterobacter aerogenes [Eucalyptus camaldulensis Dehnh. and Myrtus communis L. essential oils were tested against multidrug resistant Acinetobacter baumannii wound isolates. Both essential oils evidenced antibacterial effects when administered alone, but also reported synergistic effects when combined with antibiotics [Finally, it is interesting to report that some investigations evidenced that essential oils can be useful against multidrug resistant bacteria. The group of Yap evidenced in multidrug resistant nescence ,67. The erogenes . Eucalypibiotics ,70.At first, most of the essential oils were investigated for their antioxidant and anti-inflammatory properties and, consequently, for their potential use in the treatment of inflammatory diseases. Moreover, essential oils could also exert anticancer effects because there is a direct relation between the production of reactive oxygen species (ROS) and oxidative and inflammatory states that can lead to cancer ,72. On oApoptosis is a well-defined form of programmed cell death to ensure homeostasis which can be triggered by endogenous or exogenous signals. An abnormality in apoptosis process can origin various types of diseases such as cancer or autoimmune diseases. Due to the high heterogeneous composition of essential oils together with the wide types of cancers, it is quite difficult to define an exclusive mechanism of action. Many studies have reported the anticancer activity of essential oils and some of their isolated components against several cancers such as glioblastoma, melanoma, leukaemia, bone, breast, lung, ovary, pancreas and prostate cancers, among others . In most of the studies, apoptotic markers including cytoskeletal alterations, plasma membrane damage, mitochondrial dysfunction, DNA fragmentation, caspase-3 activation, and cleavage of pro-survival proteins have been reported ,77,78,79Abies balsamea (L.) Mill.  essential oil was tested against solid tumour cell lines  and reported significant cytotoxicity in all these cell lines [Zanthoxylum schinifolium Siebold & Zucc. also induced apoptotic death in HepG2 human hepatoma cells and significantly increased ROS production [Aniba rosaeodora Ducke were investigated on the human epidermoid carcinoma cell line A431 and on immortal HaCaT cells [Pinus densiflora Siebold & Zucc. inhibited the proliferation and survival and induced apoptosis in YD-8 human oral squamous cell carcinoma cells [N-terminal kinase (JNK)-1/2. Melissa officinalis L. essential oil was also tested in glioblastoma multiforme cells showing a significant induced apoptosis as it was evidenced by DNA fragmentation and caspase-3 activation [C. bergamia essential oil induced apoptotic and necrotic cell death in human neuroblastoma SH-SY5Y cells [One of the mechanisms by which essential oils can induce apoptosis is through increased generation of ROS. The ll lines . The treoduction . HoweveraT cells . The trema cells . The tretivation . The cyt5Y cells . The incBoswellia sacra Flueck. essential oil induced tumor cell-specific apoptosis in several human breast cancer cells with significant fragmented genomic DNA, caspase-3 activation and cleavage of PARP [B. sacra essential oil suppressed Akt, reducing the levels of phospho-Akt (Ser473), and ERK1/2 activation in human breast cancer cell lines except to MDA-MB-231 cells. In a further research from the same group, B. sacra essential oil also induced apoptosis in pancreatic cancer cells, but, in this case, it was associated with a transient activation of PI3K/Akt and ERK1/2 pathways [Litsea cubeba Pers. seeds induced apoptosis and cell cycle arrest in human A549 non-small cell lung carcinoma cells [Curcuma zedoaria Roxb. essential oil in the same non-small cell lung carcinoma cells [Monarda citriodora Cerv. ex Lag. activated apoptosis in human promyelocytic leukemia HL-60 cells by means of disruption of the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR signaling cascade [Pinus koraiensis Siebold & Zucc. were investigated in EOPK in HCT116 colorectal cancer cells [Another target for essential oils is the protein kinase B, also known as Akt, which regulates p53. Moreover, the Akt pathway is found to be activated in early stages of diverse cancers, and activation of Akt signalling protects cancer cells from tamoxifen-induced apoptosis ,87. Bosw of PARP . B. sacrpathways . This dima cells . The trema cells . Another cascade . The anter cells . The essArtemisia capillaris Thunb. essential oil exerted cytotoxicity in human oral epidermoid carcinoma cells [C. zedoaria essential oil in non-small cell lung carcinoma cells in addition to Akt was also mediated by ERK1/2, JNK1/2 and p38. Thymus vulgaris L. essential oil cytotoxicity was investigated towards head and neck squamous cell carcinoma UMSCC1 cell line [N-glycan biosynthesis, interferon and ERK-5 signalling pathways.Mitogen-activated protein kinases (MAPKs) are also essential targets for the essential oils as it was shown in some of data mentioned above. Diverse MAPKs including JNK, ERK and p38 kinases are involved in the apoptosis process in cancer cells. Essential oils can induce apoptosis through phosphorylated MAPKs, a process that can be favoured by ROS production . Artemisma cells . The resma cells , apoptosell line . The mosCymbopogon flexuosus (Nees ex Steud.) W.Watson induced apoptosis in a dose-dependent manner as evidenced by increased annexin V binding, DNA laddering and apoptotic bodies in HL-60 cells [Pogostemon cablin (Blanco) Benth. (patchouli) exerts anti-cancer activity against diverse human colorectal cancer cells by inducing apoptosis and decreasing cell growth [Curcuma wenyujin Y.H.Chen & C.Ling extract inhibited tumour growth in human cervical cancer HeLa cells through blockade of cell cycle progression at G1 phase and apoptosis [Cinnamomum cassia (L.) J. Presl inhibited tumor cell proliferation and induced cell death by activating pro-apoptotic molecules and inhibiting NF-κβ and activator protein-1  activities and their downstream genes such as Bcl-2, BcL-xL and survivin in a mouse melanoma model [Nuclear factors play an important role in the development of cancer and may also be affected by essential oils so they are an interesting target to be investigated. NF-κβ plays a central role in the regulation of apoptosis, oncogenesis and inflammation and is associated with cancer when over-expressed . In this60 cells . The oill growth . The propoptosis . The trema model .Cryptomeria japonica (Thunb. ex L.f.) D. Don on human oral epidermoid carcinoma cells could be also mediated by mitochondrial stress and activation of caspases [C. wenyujin activated the mitochondrial apoptotic pathway in human cervical cancer HeLa cells as it was evidenced by a decrease in myeloid cell leukemia sequence 1 (Mcl-1) and Bcl-xL levels, leading to mitochondrial membrane potential loss and caspase activation [Artemisia vulgaris L. essential oil against HL-60 cells is mediated by a mitochondria-dependent apoptosis [Cephalotaxus griffithii Hook. f. needle essential oil on human cervical cancer cells  evidenced a mitochondria-initiated apoptosis [Finally, mitochondrion is another key target for essential oils as this organelle can initiate apoptotic processes. The apoptotic effects of caspases . In facttivation . The cytpoptosis . The esspoptosis . The essOriganum syriacum var. bevanii (Holmes) letsw.), thyme (Thymbra spicata L. subsp. spicata), lavender (Lavandula stoechas L. subsp. stoechas), rosemary , fennel (Foeniculum vulgare Mill.) and laurel (Laurus nobilis L.) against tomato late blight disease agent Phytophthora infestans and tomato grey mould disease agent Botrytis cinerea. The treatment with the essential oils provoked the loss of integrity of the cell wall and plasma membrane permeability with important morphological alterations in hyphae. The antifungal activity of phenolic-rich Lavandula multifida L. essential oil has been evidenced against Candida albicans [Curcuma longa L. was cytotoxic for Aspergillus flavus, and inhibited aflatoxin production. Analysis with scanning electron microscopy reported significant damage to hyphae membranes and conidiophores in A. flavus exposed to the essential oil. The antifungal effects of Thymus eriocalyx (Ronniger) Jalas and Thymus x-porlock essential oils were studied in Aspergillus niger. Transmission electron microscopy reported that A. niger exposed to essential oils reported irreversible damage to cell wall, cell membrane and diverse cellular organelles. Matricaria chamomilla L. flower essential oil was probed against A. niger growth and ultrastructure [Natural products with antifungal properties are also an interesting new therapeutic alternative to the synthetic drugs. These products also become more important by the fact that, similar to bacteria, fungal drug-resistant strains are increasing rapidly . Many stalbicans . The apoalbicans  showed ttructure . The resCinnamomum jensenianum Hand–Mazz essential oil showed significant alterations in plasma membrane, fibrillar layer, and cytoplasm of A. flavus [Coriaria nepalensis Wall. essential oil cytotoxicity was examined against fluconazole-sensitive and -resistant Candida isolates [Candida isolates by disrupting membrane integrity and also inhibiting ergosterol biosynthesis. The treatment with the essential oil from Ocimum sanctum L. induced significant cytotoxicity in C. albicans cells [Coriandrum sativum L. essential oil was also reported to bind to membrane ergosterol, increasing ionic permeability and inducing membrane damage which leads to cell death in different Candida strains [C. sativum essential oil decreased the proteolytic activity of C. albicans. Similar results were reported when treating Candida strains  with Mentha piperita L. essential oil [In addition to ultrastructural alterations, some studies investigated the mechanisms underlying the pro-apoptotic effects of essential oils. In a study, . flavus . Mitocho. flavus . Coriariisolates . The essns cells . This ef strains . In additial oil . ExposedAnethum graveolens L. seed essential oil was reported to induce apoptosis in an human pathogen C. albicans strain as it was clearly evidenced by a decrease in ATPase activity, chromatin condensation, DNA fragmentation, and phosphatidylserine exposure, cytochrome c release and metacaspase activation [l-cysteine was able to prevent apoptosis indicating that ROS participated in the essential oil-induced apoptosis. In an investigation by Ferreira et al. [M. piperita cytotoxic to the yeast Saccharomyces cerevisiae was associated with increased levels of intracellular ROS, mitochondrial destruction and chromatin condensation, without loss of the plasma membrane integrity.Induction of ROS overproduction and oxidative stress has been also reported to mediate the cytotoxic effects of essential oils. tivation . In thisa et al. , the essEphedra major Host essential oil reduced growth and aflatoxin production by Aspergillus parasiticus [Chenopodium ambrosioides L. was cytotoxic against a broad number of fungi and also inhibited the aflatoxin B1 production by the aflatoxigenic strain of A. flavus [T. eriocalyx and Thymus x-porlock significantly inhibited A. parasiticus growth, aflatoxin production and induced irreversible damage in cell membranes [A. flavus after treatment with diverse essential oils such as Piper betle L. var. magahi [Zataria multiflora Boiss. essential oil reduced growth and aflatoxin production in A. parasiticus [Z. multiflora oil on toxin production were associated to an inhibition of the genes of aflatoxin biosynthesis pathway.Another point to take into account is the production of mycotoxins which can be toxic for humans. Aflatoxins are very harmful fungal toxins and, consequently, the potential effects of natural compounds against toxin production are of great interest . In accoasiticus . The ess. flavus . The essembranes . Antifun. magahi ,124,125.asiticus . The inhPlasmodium falciparum and Leishmania donovani are protozoan parasites which are becoming resistant to conventional drugs, and this leads to an increase of the mortality and morbidity rates [Plant essential oils can be used as alternatives against endo- and ectoparasites. In this way, ty rates ,128. In ty rates . Some auLavandula angustifolia Mill. and Lavandula x intermedia essential oils were assayed against the human protozoal pathogens Giardia duodenalis and Trichomonas vaginalis and also against the fish pathogen Hexamita inflata [C. ambrosioides evidenced significant cytotoxic effects against intracellular amastigote form [Piper cubeba L.f. was active against Schistosoma mansoni [Cymbopogon species, C. citratus (DC) Stapf., C. giganteus Chiov., C. nardus (L.) Rendle and C. schoenantus (L.) Spreng. were cytotoxic when tested against Trypanosoma brucei brucei and Plasmodium falciparum [Ocimum gratissimum L. [Artemisia indica Willd. oil showed in vitro antimalarial activity, in addition to potential malaria prophylactic effect [Artemisia absinthium L. showed toxic activity on two parasitic protozoa Trypanosoma cruzi and Trichomonas vaginalis [Tetradenia riparia leaves and Foeniculum vulgare Mill. decreased the number of eggs produced and the percentage of developed eggs in Schistosoma mansoni [The antiparasitic activity  inflata . Both esote form ,132. The mansoni . The esslciparum . The samsimum L. . In anotc effect . The essaginalis . Respect mansoni .Hesperozygis ringens (Benth.) Epling. essential oil was tested on engorged females and larvae of the cattle tick Riphicephalus (Boophilus) microplus [R. microplus [C. longa and the members of the Lippia genus the most effective and the Croton genus the worst. Essential oils were also effective against host-seeking nymphs of the lone star tick, Amblyomma americanum, being oregano essential oil the most effective [Chrysopogon zizanioides (L.) Roberty essential oils were assayed on Amblyomma cajennense and Rhipicephalus microplus (Acari: Ixodidae), and promising cyototoxic effects were documented [Leishmania amazonensis and treated with C ambrosioides essential oil for 15 days [C. ambrosioides showed higher toxic activity compared with animals treated with the conventional drugs glucantime, amphotericin B, and pentamidine.Diverse studies also reported evidences of cytotoxicity against ectoparasites such as ticks and mites. The toxicity of icroplus . Anothericroplus . All essffective . The acacumented . Finally 15 days . The treArtemisia annua L. leaf essential oil against visceral Leishmaniasis induced by Leishmania donovani [Syzygium aromaticum (L.) Merr. & L.M.Perry against promastigotes and intracellular amastigotes [P. betle landrace Bangla Mahoba essential oils differing in their content of eugenol against visceral Leishmaniasis [L. donovani associated to generation of ROS targeting the mitochondria without any cytotoxicity towards macrophages. Thymus capitellatus Hoffmans. & Link essential oil also reported anti-parasitic activity on Leishmania species [The molecular mechanisms associated to the antiparasitic effects of essential oils were investigated using donovani . The cytstigotes . In bothmaniasis . The tes species . TransmiEssential oils have been used for over 5000 years for a variety of different purposes, including personal care , foods, home care, repellents for humans and animals , and health-promoting agents for the treatment of various diseases. Despite differences in chemical composition of essential oils obtained from different plants with diverse preparation methods, their main constituents belong to the same chemical classes, such as mono- and sesquiterpenes , aldehydEucalyptus (Myrtaceae), native to Australia, is one of the most widely distributed planted genera worldwide. It includes approximately 900 species, of which about 300 species contain volatile oil and under 20 species have traditionally been used as herbal remedies. Antiseptic, antimicrobial, anti-inflammatory and antipyretic properties have been ascribed to the essential oils of certain Eucalyptus species, such as Eucalyptus globulus Labill., Eucalyptus citriodora Hook., Eucalyptus gunnii Hook. f., and Eucalyptus camaldulensis Dehnh. The essential oils extracted from these species are used in traditional medicine to cure various human ailments, such as diarrhea and chronic dysentery, infections of the upper respiratory tract , and toothache and oral infection [Eucalyptus essential oil has been used as an antiseptic wash to sterilize sores, cuts, and skin infections [Many examples of essential oils used in traditional medicine can be cited. The genus nfection . Moreovefections .Mentha genera, which belongs to Lamiaceae botanic family, include species (Mentha piperita L. and Mentha spicata L.) which grow worldwide and are cultivated on a large scale for their flavoring properties used for food and cosmetic products. Mint essential oil, obtained from mint leaves, was used for its healthy properties by many cultures in ancient times, including the Assyrians, the Babylonians, the Persians, the Carthaginians, and the Greeks. The main medicinal properties these traditions ascribed to mint essential oil include carminative properties, anti-inflammatory, analgesic, and antispasmodic activities, and diaphoretic, diuretic, and emmenagogue effects. In addition, the essential oils of some species of mint have often found external use for their astringent, rubefacient, antiseptic, and antimicrobial properties as well as the treatment of neuralgia, myalgia, headaches and migraines [Syzygium aromaticum (L.) Merr. & L. M. Perry (Myrtaceae), has found various medicinal purposes in Chinese Medicine. It has been used for mouth, skin, and genitourinary health for its antimicrobial properties. In fact, clove oil is active against oral bacteria associated with dental caries and periodontal disease, Staphylococcus aureus, involved in the pathogenies of acne, and Candida albicans, which is the most common infectious agent, responsible for mucocutaneous candidiasis . Moreover, undiluted clove essential oil has been traditionally used on gums for its anti-inflammatory properties, aiding in the treatment of toothache and various dental disorders. In addition, clove oil is used for the treatment of digestive disorders and gastrointestinal diseases in Ayurvedic medicine, acting as a carminative [igraines . Clove eminative ,152.Myristica fragrans Houtt. (Myristicaceae). Arabian Traditional Medicine used this essential oil as a remedy for digestive disorders (stomachache) for its analgesic and carminative properties, and its ability to stimulate the secretion of digestive enzymes and gastric juices. Moreover, it has been used for its aphrodisiac effects. Traditional Chinese Medicine used nutmeg essential oil for its analgesic properties, to treat dysmenorrhea, painful menstruation, abdominal pain and liver problems. Ayurvedic uses of nutmeg essential oil include memory improvement and tonic effects on nervous, respiratory, and circulatory functions [Another example of an essential oil widely used in several traditional medicines is nutmeg essential oil, which is extracted through steam distillation of ground seeds of unctions ,154,155.Olea europaea L., Oleaceae), castor oil  and hemp  [The medical use of oils in Traditional Persian Medicine (TPM) dates back prior to 637 AD . Howeverabaceae) ,158.Generally, pharmaceutical dosages of medicinal oils were prepared by two primary methods: direct extraction from the herbs via compression of oil-bearing components or distillation of aromatic plant parts, or indirect, which involved the extraction of plants to prepare vegetable oils . In the Medicinal oils (Adhaan) have been used in TPM for thousands of years to treat various ailments. Currently, many of these formulations are used as ethnomedical preparations by traditional practitioners in Iran . The effSeveral traditional oils were prepared by a boiling and evaporation method , in whicMedicinal oils have been traditionally used via topical, oral and even nasal routes to target particular areas of the body to combat specific ailments. Oils for gastrointestinal, respiratory, urinary and reproductive interventions were administered orally, while the nasal route was considered for disorders affecting the central nervous system. Topical forms were most often applied for nervous, musculoskeletal and integumentary afflictions. Some traditional applications reported in the Persian literature correspond to current applications. Out of the cited medicinal oils, 31 herbs comprised the main components and reportedly showed pharmacological effects in medieval Persian reports, in which analgesic and anti-inflammatory activities were the most relevant pharmacological properties. Most of the effects have been confirmed by recent in vitro or in vivo studies. Only one study on humans relevant to the traditional report was found ; hence, Notably, only a few pharmacological effects of essential oils noted in the ancient literature can be directly matched to current reports, such as clove and damask rose oils as analgesic agents ,166, cinOver the past decade, a great interest has been focused by the Iranian medicine on the use of plant oils in the treatment of epilepsy. Although no clinical study is available as regards this application, several in vivo experiments would corroborate a potential anticonvulsant activity of many traditional Iranian essential oils.Eugenia caryophyllata Thunb (Myrtaceae), an antiepileptic remedy in Iranian traditional medicine, against seizures induced by maximal electroshock (MES) or pentylenetetrazole (PTZ) in male mice. The essential oil obtained by distillation of dried buds was administered to male mice (21–28 g) at increasing concentrations (2.5–100 µL/mL) in a volume not higher than 10 mL/kg of body weight, using sesame oil as control. Then, seizures were induced by employing each of the following methods: PTZ (1.0%) at the dose of 85 mg/kg  injected i.p. to induce clonic-tonic convulsions in animals; electroconvulsive shock  to induce tonic hind limb extension. Essential oil at the dose of 0.050 mL/kg and higher, significantly suppressed tonic electroshock-induced convulsions and mortality only at a 10 min injection–stimulation interval, while increased the dose of i.v. infused PTZ required to produce general clonus in unrestrained mice , in a dose-dependent manner. Essential oil up to dose of 0.1 mL/kg had no anticonvulsant activity against PTZ-induced tonic–clonic seizures. By adopting a similar experimental protocol, the same authors have demonstrated analogous effects of EO from Pimpinella anisum L. (Umbelliferae) fruits [Laurus nobilis L. (Lauraceae) leaves. In all of these studies, the anticonvulsant activity observed may be related mainly to eugenol, estragole, and carvacrol, present in the plants [Pourgholami et al.  have eva) fruits , and Say) fruits  have dese plants , and pree plants .More recent studies have highlighted much attention on the antimicrobial properties, especially antifungal activity, of different traditional Iranian essential oils.Heracleum persicum Desf. ex Fisch., C. A. Mey. & Avé-Lall. (Umbelliferae) against six bacterial , and two fungal strains . None of the essential oils showed significant activity against Gram negative, Gram positive or fungal microorganisms.Firuzi et al.  have tesPulicaria vulgaris Gaertn essential oil against Gram-positive bacteria (Bacillus cereus and Staphylococcus aureus), Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) and fungi . Results of antibacterial test of P. vulgaris essential oil showed that all assayed concentrations significantly (p < 0.05) inhibited the growth of B. cereus, S. aureus, E. coli, and P. aeruginosa. Minimum inhibitory concentrations (MICs) for B. cereus, S. aureus, E. coli, P. aeruginosa were 17.5, 25.2, 19.4, and 33.2 μg/mL, respectively. Antifungal screening of the essential oil of P. vulgaris showed that the oil significantly inhibited the growth of A. niger and C. albicans .Sharifi-Rad et al.  investigXanthium strumarium L. against Gram-positive and Gram-negative bacteria and fungi The antibacterial and antifungal screening of the essential oil showed that all assayed concentrations significantly inhibited the growth of Staphylococcus aureus, Bacillus subtilis, Klebsiella pneumoniae, Pseudomonas aeruginosa, Candida albicans and Aspergillus niger .Sharifi-Rad et al.  evaluateStreptococcus mutants, S. salivarius, Enterococcus faecalis, Staphylococcus aureus, Candida albicans and C. glabrata.Sharifi-Rad et al.  have repLallemantia royleana Benth. Antibacterial screening of L. royleana essential oil showed that all assayed concentrations significantly (p < 0.05) inhibited the growth of Staphylococcus aureus, Bacillus subtilis, Klebsiella pneumoniae and Pseudomonas aeruginosa. MICs for S. aureus, B. subtilis and K. pneumoniae were 5.6, 4.8 and 3.5 μg/mL, respectively; L. royleana oil was inactive against P. aeruginosa in this study. Also antifungal screening showed that essential oil of L. royleana significantly inhibited the growth of Candida albicans and Aspergillus niger .The same authors  investigZataria multiflora Boiss. EOs, an Iranian thyme-like medicinal plant, on the growth and sporulation of Aspergillus niger both in vitro and on lime fruits. In vitro antifungal assays were carried out by measuring direct fungal inhibition of essential oil for both mycelial growth and sporulation, at different concentrations (500–2000 µL in 0.5 mL Tween 80), while fruits wounded and inoculated with 0.1 mL of spore suspension (105 spores/mL) of A. niger were dipped into 200, 400 and 600 µL/L concentrations of essential oil. EC50 of essential oil for mycelial growth in direct method was 819.3 µg/L, which indicates a 50% reduction in fungal growth at this concentration. Mycelial growth of fungal cultures with essential oil treatment was significantly reduced by up to 8 days post-incubation. Furthermore, a significant positive correlation was observed between percent mycelial growth inhibition and essential oil content. The fungal growth was completely prevented at 2000 mg/L. Essential oil of Z. multiflora also significantly inhibited sporulation of A. niger. Fungal sporulation decreased steadily by increasing essential oil concentrations, and at concentration ≥1500 mg/L, no sporulation occurred. The results showed that the storage life of fruits treated with 600 mg/L essential oil in the cold room was increased by 50 days, and compared with control, fruit rot started with a 10-day delay. Only 15% of the fruits treated with 600 mg/L essential oil and stored in the cold room were rotten at 50 days of storage. Other interesting findings due to the essential oil treatment were the increase of storage and shelf life of lime fruits and no changes in the appearance and quality of the fruits. Among other studies reporting similar appreciable results concerning the effects of essential oils from typical Iranian plants on fungal strains of agricultural and food interest [Candida zeylanoides activity of the essential oils of five Iranian medicinal plants, namely Trachyspermum copticum (L.) Link., Z. multiflora, Nigella sativa L., Ziziphora clinopodioides Lam. and Heracleum persicum Desf. ex Fisch., C.A.Mey. & Avé-Lall. Clinical strains of C. zeylanoides, obtained from different parts of subjects’ genitalia, were incubated with essential oils isolated by water distillation from the aerial parts and seeds, and tested in comparison with reference standards, such as fluconazole, ketoconazole and nystatin. The essential oils of T. copticum and Z. multiflora showed a significant (p < 0.05) antifungal activities against C. zeylanoides, while the essential oils of the remaining plants showed a moderate to weak inhibition. In a previous study conducted by Naeini et al. [Z. multiflora showed a significant (p < 0.05) antifungal activity against C. albicans, while the essential oils of Z. clinopodioides, N. sativa and H. persicum exhibited a moderate to weak inhibition. Although essential oil concentrations were high when compared with those of the antifungal drugs, these results are of interest as dealing with complex mixtures and not a pure product. Shokri et al. [T. copticum oil. Z. multiflora main components were carvacrol (61%) and thymol (25%). Trans-anthol (39%) and r-cymene (17%) were identified from N. sativa oil. The GC/MS analysis of Z. clinopodioides and H. persicum essential oils showed pulegone (37%) and aperitone (19.6%), and hexyl butyrate (30.2%) and octyl acetate (12.8%), respectively, as main constituents.Abdollahi et al.  have deminterest ,185, Shointerest  have suci et al. , the essi et al.  have indLavandula angustifolia Mill.) essential oil, whose peculiar chemical composition has been indicated as responsible for many of the biological effects observed.Very recent clinical trials have highlighted specific positive effects of traditional Iranian essential oils on both the physiological conditions and psychological sphere in human subjects. Interestingly, the most significant in human studies have focused the attention on the healthy potential of lavender  in reducing the score of symptoms . Moreover, the estimated odds of moderate and heavy bleedings in the lavender group were 1.4, 0.7 and 0.3 times the estimated odds of moderate and heavy bleedings in the control group in the first, second and third day of menstruation, respectively.Lavender essential oil has been also tested for its potential effects on the symptoms of primary dysmenorrhea and the amount of menstrual bleeding through inhalation . A randoA further investigation on the potential bioactivity of lavender essential oil through inhalation has consisted in assessing its effects on stress and vital signs in patients undergoing coronary artery bypass graft surgery (CABG) . A singln = 50) and the control (n = 50). Spielberger’s state anxiety inventory with 20 items and the VAS questionnaire  were filled out by the two groups before and after aromatherapy. Lavender patients inhaled essential oil for 60 s and, to be stable, the patient’s nose was shortly massaged with the extract, whereas the control group was treated with 0.1% lemon using the same procedure. This study revealed that the apparent anxiety level in patients who inhaled lavender essential oil was noticeably lower than before intervention results and also compared with control group, especially at the levels of severe and highly severe anxiety. The mechanism of action of lavender essential oil has not been completely investigated, but, according to various studies, its psychological effects may derive by affecting limbic system, especially amygdala and hippocampus, where there could be activities similar to benzodiazepines and gamma aminobutyric acid [Another interesting in human study regarding the influence of lavender essential oil on the psychological sphere concerns its effects on preoperative anxiety in patients undergoing diagnostic curettage . In thisric acid . Accordiric acid , linalooAyurveda, the classical Hindu traditional medicine, has been in practice in many countries for centuries. Ayurvedic medicine can be defined as the administration of oral remedies according to the principles of Ayurveda. One of the key concept of Ayurveda is Svastha, or a healthy living being . This isSeveral scientific studies are on-going to give scientific validation for the use of the components of Ayurvedic medications; this is aimed to channel regulations and acceptance for the clinical practice. Aromatic plants which are rich in essential oils represent one of the major ingredients of Ayurvedic medications. The use of essential oils in Ayurvedic traditional and complementary medicine is gaining more popularity over the years. This is due to their well-studied biological effects which include antimicrobial ,202, phsDiabetes mellitus (DM) is characterized by hyperglycemia (high blood glucose levels) due to the inability of the pancreas to produce enough insulin or of the cells to respond to the insulin that is produced . Type 2 Ocimum basilicum L.) leaves was investigated in vitro on α-amylase, α-glucosidase and angiotensin-I-converting enzymes (ACE). In addition, these authors also investigated the antioxidant properties of the essential oil via inhibition of Fe2+ and sodium nitroprusside (SNP)-induced lipid peroxidation in rats’ pancreas and heart tissue homogenates. The phytoconstituents of the oil were analyzed using gas chromatography (GC). Sweet basil essential oil inhibited the activities of α-amylase (IC50 = 3.21 mg/mL), α-glucosidase (IC50 = 3.06 mg/mL) and ACE (IC50 = 0.89 mg/mL), as well as both Fe2+ and SNP-induced lipid peroxidation in tissue homogenate. The bioactivities were largely correlated with the main constituents of O. basilicum essential oil, including limonene (47.40%), borneol (8.66%), geranial (6.93%), neral (5.71%), myrcene (4.68%), β-caryophyllene (4.68%), α-terpineol (4.60%), 1,8-cineole (4.17%), linalool (3.53%), β-elemene (3.05%), germacrene D (2.68%), and terpinen-4-ol (2.21%). Hence, this plant species widely known in Ayurvedic practices could offer protection against diabetes and its complications via its enzyme inhibitory and antioxidant properties.In a study conducted by Ademiluyi et al. , the inhEugenia aromatic O.Berg). Clove bud is a spice of vast culinary and medicinal values. Its bioactive properties have been largely ascribed to its constituent phytochemicals such as the terpenoids, monoterpenes and sesquiterpenes. In their study, Oboh et al. [Piper guineense Schumach. & Thonn.) seeds, in an in vitro system by assessing their α-amylase, α-glucosidase (key enzymes linked to type-2 diabetes), and angiotensin-I converting enzyme (ACE) (key enzyme linked to hypertension) inhibitory activity. According to them, the essential oil inhibited the three enzymes concentration dependently, while also exhibiting significant antioxidant activity. These bioactivities were attributed to the individual compounds in the essential oil which GC characterization revealed to include α-pinene, β-pinene, cis-ocimene, myrcene, allo-ocimene, and 1,8-cineole. Therefore, they concluded that the phenolic content, antioxidant activity, and inhibition of α-amylase, α-glucosidase, and angiotensin-I converting enzyme activities by the essential oil extract of black pepper could be part of the mechanism by which it could be used to manage and/or prevent type-2 diabetes and hypertension.In another study, Oboh et al.  investigh et al.  observedh et al.  also stuSalvia species such as Salvia aurea L., Salvia judaica Boiss. and Salvia viscosa Jacq. are popular among many local indigenes for the therapeutic properties of their essential oils [Salvia species are often used as Ajurvedic components in many multiherb products commonly patronized in Lebanon and surrounding countries for the treatment of cancer and other diseases [Salvia species, as well as their biological activity against human melanoma cells and the anticancer mechanisms involved, as cell membrane integrity, genomic DNA fragmentation and caspase-3 activity. The authors reported that all the essential oils were able to decrease the growth of cancer cells by inducing apoptotic cell death. These activities were associated to their constituents which predominantly includes sesquiterpenes, particularly oxygenated sesquiterpenes with caryophyllene oxide.According to traditional Lebanese medicine, ial oils . These Sdiseases ; neverthdiseases  investigS-2-(3-aminopropyl-amino) ethyl phosphorothioic acid (WR-2721), amifostine, ethiophos, and gammaphos are toxic especially at their optimal concentrations which greatly limits the therapeutic benefits they offer [Radiotherapy is a treatment option in oncological practices. However, the search for radioprotective agents to selectively protect non-target tissues against radiation injury is a pivotal and current topic ; this wiey offer ,214,215.Ocimum sanctum L. popularly known as the Holy Basil is an aromatic herb that belongs to the family Lamiaceae [amiaceae . The plaamiaceae . Tulsi iamiaceae . This plamiaceae ,216,217.Phytochemical profiling of the leaf of Tulsi has revealed that it is rich in volatile oil with eugenol, methyl eugenol, carvacrol and caryophyllene as main constituents ,216,217.Neurodegenerative diseases represent a group of chronic disorders characterized by progressive and selective decline in neuronal and cognitive functions, found in about 5% of reported cases of brain diseases . The uniSyzygium aromaticum (L.) Merr. & Perry) and Ethiopian pepper  showed neuroprotective properties in vitro by exhibiting anticholinesterase and antioxidant activities [Citrus sinensis (L.) Osbeck) [Citrus limon (L.) Osbeck) [Several studies have reported the potential neuroprotective properties of essential oil from a number of plants used either alone or in combination with other plants in many traditional medical practices. In one study, essential oil from clove bud (tivities . These etivities . In anot Osbeck)  and lemo Osbeck)  were invDespite the huge amount of preclinical studies on the pharmacological properties of essential oils, there exits a paucity of in human clinical trials. In a systematic review of randomized clinical trials by Perry et al. , lavendeTraditional Korean Medicine (TKM) is one of the traditional East Asian medical systems that, for more than 2000 years, has been used to treat several diseases, including cancer .A holistic approach including the concepts of the body-mind-spirit network, the balancing theory of Yin-Yang and Five Phases, is the basis of TKM, which is characterized by an equal emphasis on the individual’s differences as well as symptom pattern differentiation ,245. RegThe essential oils of some medicinal plants used in TKM have been investigated for their potential anticancer activity . Among tAllium sativum L. (Amaryllidaceae) has shown an anti-proliferative effect on human breast, colon, lung, skin and liver tumors [A. sativum oil increased glutathione (GSH) peroxidase activity in isolated epidermal cells incubated in the presence or absence of a tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), and inhibited the sharp decline in the intracellular ratio of reduced (GSH)/oxidized (GSSG) glutathione caused by TPA. The stimulatory effects of this oil on epidermal GSH peroxidase activity are concentration-dependent and long lasting, thus abolishing the prolonged inhibitory effect of TPA on this enzyme. In addition, garlic oil (5 µg/mL) inhibited by about 50% TPA-induced ornithine decarboxylase  activity in the same epidermal cell system. This concentration of garlic oil remarkably increased GSH peroxidase activity and inhibited ODC induction in the presence of various non-phorbol ester tumor promoters. According to these findings, it was postulated that the inhibitory effects of garlic oil on skin tumor promotion might result from the enhancement of the GSH-dependent antioxidant protective system of the epidermal cells [r tumors . In partal cells .Boswellia species (Burseraceae), which are trees native to Ethiopia, Somalia, India, and Arabic peninsula, produce a gum resin that is known as frankincense. This gum resin has long been used in Ayurvedic and traditional Chinese medicine to treat a variety of health aspects [ aspects . The mai aspects  and meni aspects , as well aspects .Boswellia serrata Roxb. ex Colebr. volatile oil revealed the presence of sabinene (19.11%), terpinen-4-ol (14.64%) and terpinyl acetate (13.01%) as major constituents. Treatment of HepG2 cells with volatile oil showed a significant and dose-dependent reduction of cell viability with IC50 value of 5.5 g/mL after 48 h. Likewise, the treatment of HCT116 cells resulted in a dose-dependent decrease in cell viability with IC50 value of 6.2 μg/mL after 48 h [Gas chromatography-mass spectrometry (GC-MS) analysis of the ter 48 h .Artemisia capillaris Thunb. (Compositae) has been used in traditional Korean medicine for their interesting biological activities including antioxidant, anti-inflammatory, hepatoprotective and anticancer properties [A. capillaris essential oil to induce apoptosis in the human oral epidermoid carcinoma cell line KB. The oil included capillene (32.7%), α-caryophyllene (11.1%), and α-pinene (9.4%) as main constituents [A. capillaris essential oil treatment was observed. Moreover, condensation and fragmentation of nuclei, and cellular shrinkage (distinctive apoptotic features) were evidenced in the cells after treatment with the oil (at a concentration of 0.5 μL/mL for 12 h). After treating KB cells with the A. capillaris essential oil, the concentration-dependent activation of caspase-8 was observed. The involvement of the c-Jun N-terminal kinase (JNK)/Bcl-2-mediated and p38/nuclear factor-kappaB (NF-κβ) pathways as well as caspase activation in the A. capillaris essential oil-mediated apoptosis was also demonstrated.operties ,268. Chaoperties  investigtituents . The essArtemisia iwayomogi Kitam. (Compositae) is a small herbal plant that has long been used in traditional Korean medicine as chemopreventive agent [A. iwayomogi essential oil revealed the presence of camphor (19.31%), 1,8-cineole (19.25%), borneol (18.96%), camphene (4.64%), and α-caryophyllene (3.46%) as the most abundant compounds [A. iwayomogi essential oil induced apoptosis of KB cells, mediated by mitogen-activated protein kinases (MAPKs). A. iwayomogi essential oil induced the cleavage of PARP and the activation of caspases. An imbalance between the mitochondrial levels of Bcl-2 and Bax was also observed. Moreover, pre-treating the cells with caspase or MAPK-specific inhibitors apparently inhibited cytotoxicity of KB cells induced by the essential oil.ve agent . The cheompounds . The potompounds . A. iwayArtemisia species used in TKM is A. lavandulaefolia Nakai. The effects of A. lavandulaefolia essential oil on apoptosis and necrosis of human cervix adenocarcinoma (HeLa) cell line were investigated [A. lavadulaefolia essential oil (at concentration of 100 and 200 g/mL for 24 h), HeLa cells showed cell shrinkage and nucleus chromatin condensation that are typical morphological features of undergoing apoptosis. However, at the concentration 400 g/mL, HeLa cells showed necrotic morphology changes. Furthermore, the cleavage of PARP was inactivated and the caspase-3 was activated. The major constituents of the A. lavandulaefolia essential oil were α-caryophyllene (16.1%), cis-chrysanthenol (7.0%), 1,8-cineole (5.6%), borneol (5.3%), trans-α-farnesene (5.1%), and camphor (4.9%) [Another stigated . The oilr (4.9%) .Pinus koraiensis Siebold & Zucc. (Pinaceae)  is an evergreen tree found in Korea, China, Japan, and eastern Russia. P. koraiensis essential oil contains different constituents, including limonene, camphene, 4-carene, α-pinene, and α-phellandrene [P. koraiensis essential oil reduced the proliferation of HCT116 cells through G1 arrest, inhibited cell migration, altered cytoskeletal structure through the reduction of basal spread and cell elongation and increased cell rounding.landrene . The antlandrene . P. koraSolanum (Solanaceae) comprises around 1700 species commonly found in the temperate and tropical regions of the world. Several Solanum species are used in Asiatic traditional medicine. Solanum nigrum L. is one of the herbal ingredients in prescriptions of Traditional Chinese Medicine to treat liver, mammary, uterine cervix, gastric and other cancers [The genus  cancers .Solanum spirale Roxb. essential oil from unripe fruits was analyzed for its chemical composition and anticancer activity. n-Hexadecanoic acid (56.01%), linoleic acid (9.71%), octadecanoic acid (4.41%), methyl palmitate (1.69%), tetradecanoic acid (1.55%), (E)-phytol (1.18%), n-hexanal (0.91%), methyl salicylate (0.83%), 4-hydroxy-4-methylpentan-2-one (0.81%), pentadecanoic acid (0.71%) and β-selinene (0.56%) were identified as main constituents. The oil exhibited anticancer activity against breast cancer cell line (MCF-7) and small cell lung cancer (NCI-H187) with IC50 values of 23.17 and 49.07 g/mL, respectively. No cytotoxic activity was found against KB cell line [S. spirale leaves showed significant cytotoxicity against oral cancer cells (KB), breast cancer cells (MCF-7) and small cell lung cancer cells (NCI-H187) with IC50 values of 26.42, 19.69, and 24.02 μg/mL, respectively. (E)-Phytol (48.10%) was the most abundant compound followed by n-hexadecanoic acid (7.34%), α-selinene (3.67%), α-selinene (2.74%) [ell line . The ess (2.74%) .Solanum stipulaceum Roem. & Schult. flowers. β-Caryophyllene (25.8%), caryophyllene oxide (3.6%), γ-gurjunene (11.9%), α-gurjunene (8.2%), α-selinene (5.3%), and α-humulene (2.7%) were identified as main compounds. The essential oil showed antileukemic activity against both human acute promyelocytic leukemia (HL-60) and acute monocytic leukemia (THP-1) cells after γ-radiation (10.0 kGy), with IC50 values of 86.67 and 40.12 g/mL, respectively. β-Caryophyllene, one of the major constituents identified in this essential oil, has been reported as a cytotoxic agent against human cancer cell lines. This sesquiterpene inhibited the constitutive activation of PI3K/AKT/mTOR/S6K1 signaling cascade, but also caused the activation of ERK, JNK, and p38 MAPK in tumor cells. Moreover, it increased reactive oxygen species (ROS) generation from mitochondria, which is associated with the induction of apoptosis, down-regulated the expression of various downstream gene products that mediate cell proliferation (cyclin D1), survival , metastasis (COX-2), angiogenesis (VEGF), and increased the expression of p53 and p21 [trans-caryophyllene was active against renal cell adenocarcinoma (ACHN) and amelanotic melanoma (C32) cell lines, with IC50 values of 21.81 and 20.10 g/mL, respectively [50 value of 11.24 g/mL. This sesquiterpene was inactive against the breast cancer (MCF-7), C32, and ACHN cell lines at the maximum concentration tested (50 g/mL).Osorio et al.  investig and p21 . In prevectively ,274. AnoSolanum species recently reported as cytotoxic are Solanum erianthum D.Don and Solanum macranthum Dunal. S. erianthum leaf volatile oil demonstrated potent inhibitory activity against human breast carcinoma (Hs 578T) and prostate carcinoma (PC-3). In particular, S. erianthum exhibited 98.85 and 97.94% of cell mortality against Hs 578T and PC3, respectively, while S. macranthum oil exhibited 2% mortality against breast cancer cells. S. erianthum oil was characterized by the abundance of α-terpinolene (17.8%), α-phellαndrene (17.5%), p-cymene (15.7%) αnd α-pinene (11.7%) in the leαves; α-humulene (23.1%), humulene epoxide II (20.0%), cαryophyllene oxide (16.5%), methyl sαlicylαte (11.8%) αnd α-cαryophyllene (10.9%) in the fruits. The leαf oil of S. mαcrαnthum consisted of (E)-phytol (29.0%), pentαdecαnαl (28.1%) αnd pentαdecαne (7.7%), while the mαjor fruit oil constituents were α-humulene (36.5%), α-caryophyllene (17.8%), ethyl palmitate (9.4%), and methyl salicylate (8.2%) [Other e (8.2%) .Vitex rotundifolia L.f. (Verbenaceae) has long been used in Korean traditional medicine to treat asthma and other allergic diseases [V. rotundifolia also showed strong estrogenic activity. Hu et al. [V. rotundifolia could significantly stimulate the growth of MCF-7 cells and the proliferation stimulatory effect could be reversed by co-administration of a pure anti-estrogen .diseases . Dried fu et al.  identifiCurcuma longa L. (turmeric) is a perennial from the Zingiberaceae family that is widely cultivated in the tropical regions of Asia. This genus is composed of about 70 species of rhizomatous herbs, which are distributed all over the world. Turmeric contains up to 5% essential oils. An isolate from turmeric oil has been reported to have antimutagenic activity thought to be mediated through its antioxidant activity [C. longa rhizome is a complex mixture obtained by steam distillation, and twelve components were identified by GC-MS analysis: ar-turmerone (61%), curlone (11.2%), and cucumene (5.5%) were the most abundant compounds [activity . The essompounds .C. longa essential oil has significant antimutagenic activity against mutagens needing metabolic activation, such as 2-acetamidoflourene, and inhibites the mutagenicity induced by tobacco extract to Salmonella TA 102 strain. DMBA and croton oil induced papilloma development in mice was found to be delayed and prevented significantly by its application. Results clearly evidenced that C. longa essential oil inhibited isoforms of cytochrome p450  enzymes in vitro, which are involved in the activation of carcinogens.Liju et al.  demonstrC. longa oil was also tested against human mouth epidermal carcinoma (KB) and murine leukemia (P388) cell lines using MTT assay. The turmeric oil showed IC50 values of 0.0838 and 1.0879 mg/mL for P388 and KB cell lines, respectively [ectively . Structuectively .Curcuma aromatica Salisb. oil was studied for its antioxidant and anticancer activities on esophageal carcinogenesis. Severe esophagitis was evidenced in rats after esophagoduodenal anastomosis, and morphological transformation within the esophageal epithelium was observed with intestinal metaplasia after 3 months. In treated rats by i.p. injection of C. aromatica oil at 100 mg/kg, every 3 days, both MnSOD enzymatic activity and protein level were similar to controls. Decreased incidences of both intestinal metaplasia and esophageal adenocarcinoma were also observed [observed .Curcuma species used in TKM, C. zedoaria Roxb. (known as zedoary) is used for the treatment of flatulence, dyspepsia, menstrual disorders, cough, and fever. The zedoary essential oil exhibited anti-proliferative activity on mouse melanoma cells (B16BL6) and human hepatoma cells (SMMC-7721) with IC50 values of 41.8 and 30 g/mL, respectively. An IC50 of 150 g/mL was found against human umbilical vein endothelial cells (HUVEC) cells. Moreover, the essential oil significantly suppressed the sprouting vessels of aortic ring and formation of microvessels in chick embryo chorioallantoic membrane. Additionally, solid melanoma grown in left oxter of mice was inhibited after oral intake of 100 and 200 mg/kg of the oil once a day for 28 days, and CD34 expression indicating angiogenesis in melanoma reduced significantly compared with control; melanoma metastatic nodules in lung were also inhibited, as well as MMP-2 and MMP-9 expression in serum [Among in serum .50 values ranging from 80 to 170 g/mL in H1299 cells. The essential oil increased the sub-G1 population and the level of annexin-V binding, and induced cleavage and activation of caspase-3, -8, and-9 and poly(ADP ribose) polymerase. It decreased the levels of Bcl-2 and Bcl-xL and determined an increase in the Bax/Bcl-2 ratio. The release of AIF (apoptosis-inducing factor), cytochrome c and endonuclease G into the cytosol, and increased levels of p53 in H1299 cells was observed. Zedoary essential oil slightly inhibited the phosphorylation of ERK1/2 and AKT/NF-κβ, and enhanced the phosphorylation of JNK1/2 and p38. The highest value of cells in apoptosis (41.6%) was observed after exposure for 72 h with characteristic hallmark of DNA fragmentations. Moreover, intraperitoneal administration of zedoary essential oil significantly suppressed the growth of H1299 cells implanted subcutaneously in BALB/c (nu/nu) nude mice. The GC-MS analysis revealed the presence of 8,9-dehydro-9-formyl-cycloisolongifolene,6-ethenyl-4,5,6,7-tetrahydro-3,6-dimethyl-5-isopropenyl-trans-benzofuran, eucalyptol, and γ-elemene as main constituents [Zedoary essential oil caused a time- and concentration-dependent inhibition of non-small cell lung carcinoma (NSCLC) cell proliferation with ICtituents .Curcuma wenyujin Y.H.Chen & C.Ling is used as ingredient of Ezhu (Rhizoma curcumae) together with C. phaeocaulis Valeton and C. kwangsiensis S. G. Lee & C. F. Liang in Asiatic traditional medicines including the Korean, Chinese and Japanese ones. This remedy is traditionally used for removing blood stasis, alleviating pain, and liver disease protection. Injection of the essential oil has been used to cure pediatric diseases such as acute upper respiratory infections, acute pneumonia or viral myocarditis [C. wenyujin oil has shown promising effects in the treatment of cervical, gastric, liver, and lung cancers [50 of 70 g/mL. The oil induced a cell cycle arrest at S/G2. This growth inhibition was associated with cell cycle arrest, cytochrome c translocation, caspase 3 activation, poly-ADP-ribose polymerase (PARP) degradation, and loss of mitochondrial membrane potential. This process involves a mitochondria-caspase dependent apoptosis pathway [carditis . Moreove cancers ,262. The pathway . Shi et  pathway  reported pathway  demonstr pathway . Furanod pathway .Over 3000 plants are sources of essential oils, though only around 300 of these are of commercial value. Approximately 30 of these latter plants, often cultivated on a large scale, produce essential oils whose use as drugs dates back centuries in different cultures throughout the world, and are described in international and national Pharmacopoeias. In Eucalyptus, Mentha, and Citrus species, are reported in the following paragraphs. These essential oils were chosen based on the number of studies reported in the PubMed database. In fact, the literature search performed in PubMed using the keywords “Eucalyptus species essential oil”, “Mentha species essential oil”, and “Citrus species essential oil” each produced about of 500 articles, while other essential oils have been studied less.Literature data published over the last five years (from 2011 up to June 2016) regarding the pharmacological properties of essential oils from Eucalyptus species have been of great interest for their potential use as drugs against infectious diseases, due to a high content of health-promoting bioactive compounds with antimicrobial activity.In recent years, the essential oils extracted from the E. globulus Labill. obtained through the hydrodistillation method (using a Clevenger-type apparatus) showed antibacterial activity against clinically isolated strains of Escherichia coli and Staphylococcus aureus by using agar disc diffusion and broth dilution methods. The diameter of the inhibition zone ranged from 8 to 26 mm. The largest diameter was registered on E. coli treated with pure essential oil, while S. aureus was found to be more sensitive than E. coli at the lowest concentrations. The authors concluded that E. globulus leaf essential oil could be used as a natural antibiotic for the treatment of several Gram-positive and Gram-negative infectious diseases.In 2012, Bachir et al.  demonstrE. benthamii Maiden & Cambage leaf essential oil (extracted from air dried young and old leaves by hydrodistillation in a Clevenger-type apparatus). In addition, some terpenes occurring in these essential oils were studied . Cytotoxicity was tested on human and experimental animal cancer cell lines  using a 3--2,5-diphenyltetrazolium bromide (MTT) assay. Moreover, the chemical compositions of the two samples were determined by gas chromatography/mass spectrometry (GC-MS), showing that the concentrations of monoterpene hydrocarbons and oxygenated sesquiterpenes were similar for essential oils obtained from either young or old leaves, while the sesquiterpene hydrocarbon and oxygenated monoterpene concentrations were higher in the essential oil extracted from young leaves than that obtained from old leaves. The results of the in vitro MTT test showed that these essential oils were more active than the isolated terpenes. Jurkat and HeLa cell lines were more sensitive to the essential oils than the murine cancer cell line, suggesting that E. benthamii leaf essential oils can be used as cytotoxic agents and potential anticancer drugs.In the same year, Döll-Boscardin et al.  publisheEucalyptus species grown in Tunisia  Maiden, E. lehmannii (Schauer) Benth. and E. leucoxylon F. Muell.). In this case, the antibacterial activity was studied against a large number of clinical bacterial isolates  using paper-disc agar and diffusion methods. The results showed that the mean diameter of inhibition for all essential oils ranged from 27.4 to 6.0 mm, while the MIC values ranged from 0.30 to 169.00 mg/mL for the most active samples. The antifungal activity was tested against five fungal strains including Candida albicans, Scopulariopsis brevicaulis, Trichophyton rubrum, Trichophyton soudanense, and Microsporum canis, using the agar incorporation method. The percentage of inhibition at a concentration of 1000 ppm was between 0.1%–100%, depending on the Eucalyptus species and the fungal strain. Finally, the antiviral activity was studied using Confluent Vero cell cultures that were treated with non-cytotoxic concentrations of the essential oils both during and after viral infection. The tested essential oils showed different activities here too, with oils from E. sideroxylon, E. lehmannii, E. leucoxylon and E. odorata having no antiviral activity, while E. bicostata (IC50 = 0.7–4.8 mg/mL), E. astringens, and E. maidennii (IC50 = 136.5–233.5 mg/mL) being the most active against viral infections. The chemical analyses performed, using GC-MS and GC/flame ionization (GC-FID) methods, led to the identification of 25 components .Elaissi et al.  extendedE. gunnii Hook. f. submitted to hydrodistillation according to Eur. Pharm. 4 [E. gunnii essential oil was significantly lower than that of synthetic antioxidant compounds. The antimutagenic activity was tested against spontaneous and t-BOOH-induced mutagenesis in E. coli IC202 oxyR, a strain deficient in removing ROS, which was treated with subtoxic essential oil concentrations ranging from 0.05 to 0.15 µL/plate. The inhibition of spontaneous mutagenesis in the presence of the essential oil was modest (12% at the highest tested concentration). The essential oil showed higher antimutagenic activity in the presence of t-BOOH-induced mutagenesis, 18% at the lowest concentration and 23% at the highest. Finally, the antibacterial activity was determined against S. aureus ATCC25923, Staphylococcus epidermidis ATCC12228, Pseudomonas aeruginosa ATCC27853, E. coli ATCC25922, Bacillus subtilis ATCC10774, Micrococcus flavus ATCC10240, Klebsiella pneumoniae NCIB9111 and E. coli SY252 and IB112 strains, using the dilution method and the disc-diffusion assay . The antibacterial activity, expressed as the diameter of the growth inhibition zone and MIC resulted to be modest. In fact, E. gunnii essential oil only showed antibacterial activity on S. epidermidis and B. subtilis under the disc-diffusion assay (at concentrations higher than 1.66 μL/mL) and on M. flavus, K. pneumoniae, and E. coli lpcA under the dilution method (MIC 0.83 mg/mL). The essential oil was submitted to GC-MS analysis for the determination of its chemical composition, and the most concentrated compounds were found to be 1,8-cineole (67.80% dry matter) followed by α-pinene (14.12%), β-phellandrene (3.92%), α-terpinyl acetate (3.27%), trans-pinocarveol (2.49), and α-terpineol (2.08%), with the other constituents found at concentrations below 1% [A more recent in vitro investigation, carried out on the air-dried leaves of Pharm. 4 , focusedbelow 1% .Eucalyptus species, with similar findings. In more detail, Sebei et al. [Enterococcus faecalis, Listeria ivanovii, and Bacillus cereus. Mekonnen et al. [E. globulus essential oil against Salmonella and Shigella species, and Trichophyton and Aspergillus species. The antifungal activity of the E. smithii F. Muell. ex R. T. Baker essential oil was also investigated by Baptista et al. [Microsporum canis ATCC 32903, M. gypseum ATCC 14683, Trichophyton mentagrophytes ATCC 9533, T. mentagrophytes ATCC 11480, T. mentagrophytes ATCC 11481, and T. rubrum ATCC 5507), suggesting a potential use for the treatment of dermatophytosis.In the last two years, three more research articles have been published on the chemical composition and antibacterial activity of the essential oils extracted from i et al.  have expn et al.  studied a et al.  showing E. camaldulensis Dehnh. is active against Acinetobacter baumannii, which is an emerging multidrug-resistant pathogen diffused worldwide. The anti-melanogenic activity of the essential oil of this plant has also been studied by means of spectrophotometric determination of the melanin content of mouse melanoma cells and cellular tyrosinase activities, and Western blotting for the evaluation of the levels of expression of melanogenesis-related proteins, after treatment with non-toxic concentrations of the essential oil extracted by hydrodistillation from the flowers of E. camaldulensis. In the same study, the authors investigated antioxidant activity, using DPPH scavenging activity and 2,2′-azino-bis(3-ethylbenzothiazolin-6-sulphonic acid) (ABTS) scavenging capacity assays to explain the potential mechanisms of action at the basis of the anti-melanogenic activity. In addition, cellular ROS levels were registered. The results showed that essential oil extracted from E. camaldulensis flowers was able to inhibit melanogenesis through its antioxidant capacity and the down-regulation of mitogen-activated protein kinase (MAPK) and protein kinase A (PKA) signaling pathways. Therefore, the authors concluded that this plant product could be used in the treatment of skin diseases [In 2016, Knezevic et al.  showed tdiseases .E. citriodora Hook. essential oil on Wistar rats fed with food mixed with this essential oil at doses ranging from 600 to 2600 mg/kg. The most abundant components of this oil were citronellal (83.50%) followed by isopulegol (4.40%) and methyleugenol (2.20%). The analgesic properties were determined using tail flick and tail immersion Koster methods. Anti-inflammatory activity was assessed by injecting 0.1 mL of 1% (v/v) formol into the aponeurosis of the left foot of the rats to cause an edema. The results showed that E. citriodora essential oil exerted in vivo analgesic and anti-inflammatory activities, suggesting a potential use as adjuvant therapeutic agent against inflammatory-related diseases.As regards in vivo studies, in 2013, Gbenou et al.  investigMentha species have been studied for their antimicrobial and anti-inflammatory properties.Over the last five years, the essential oils extracted from the leaves and flowers of Mentha x piperita L., collected during the full flowering stage. The essential oil was submitted to GC-MS analysis to determine its chemical composition, revealing that the most concentrated components were menthol (53.28%), menthyl acetate (15.10%), menthofuran (11.18%), 1,8 cineole (6.69), neomenthol (2.79%), menthone (2.45%), (Z)-caryophyllene (2.06%), germacrene D (2.01%) and numerous other substances which occurred in concentrations below 2%. The antifungal activity of this essential oil was investigated against 25 standard strains of fungi (including Candida and Aspergillus species), and 35 clinical isolates of yeasts, and the capacity to inhibit growth and biofilm formation, which is an important aspect for fungal survival and a mechanism of drug resistance. Antifungal activity, determined by means of the microdilution method using fluconazole as a positive control, was expressed as MIC and minimum fungicidal concentration (MFC). The essential oil showed high fungistatic activity against all tested strains with MIC values ranging from 0.5 to 8 µL/mL for Candida and 0.5 to 4 µL/mL for Aspergillus species, respectively. Moreover, it showed fungicidal activity against encapsulated yeasts such as C. neoformans, responsible for meningitis. In addition, the essential oil inhibited the formation of biofilms by C. albicans at a concentration of 2 µL/mL.In 2012, Saharkhiz et al.  evaluateM. piperita), possess antimycotic activity against clinical keratinophilic fungi  isolated from patients with superficial fungal infections, showing a MFC ranging from 2 to 4 µL/mL [M. piperita essential oil, as well as several standard compounds occurring in the oil , exerted anti-candida activity, with the essential oil and carvone being most active with MIC values of 225 mg/mL and 248 mg/mL, respectively. The mechanism of action was investigated by assessing (1) the enzymatic activity of plasma membrane H+ ATP-ase ; (2) H+ efflux mediated by plasma membrane H+ ATP-ase; (3) ergosterol biosynthesis; and (4) the ultrastructure of Candida cells, by means of scanning electron microscopy. At MIC values, the essential oil and its constituents induced a reduction in enzymatic activity of about 50%. Moreover, a decrease in ergosterol content, cell membrane damage, and modifications in Candida cell morphology were registered, suggesting that the antifungal activity of M. piperita essential oil has a multi-factorial mechanism [M. piperita essential oil against Gram-negative bacteria . The antibacterial activity the oil and its effects on virulence factors of P. aeruginosa and A. hyrophila  were studied, showing the capacity of this essential oil and menthol to interfere with the quorum sensing systems of tested Gram-negative bacteria. These findings are interesting because they show that an essential oil can influence the systems used by bacteria to coordinate gene expression according to the density of the microbial population, including the production of virulence factors [These results have been confirmed by a more recent study published by Ibrahim et al. which showed that several essential oils, and among these the essential oil of fresh mint leaves  or indomethacin (used as a positive control at the doses of 300 mg/ear) about 60 min before the croton oil treatment. The evaluation of the anti-inflammatory activity was tested by comparing the weight of the left (control) and right (treated) ear. The results showed that the essential oil decreased ear edema by 5.77%, 7.37%, and 30.24% at doses of 200, 400, and 800 mg, respectively, showing a similar activity to that given by the indomethacin treatment, which reduced the edema by 16.79%. These results were also confirmed in in vitro conditions. In RAW 264.7 cells stimulated with LPS and treated with the essential oil, a decrease in the production of NO and PGE2, well-known mediators in acute inflammatory responses, was registered. In the same investigation, the cytotoxic effect of M. piperita essential oil against cancer cell lines  was determined by MTT assay 24 h after treatment. The cytotoxic activity was found to be dependent on the cell line. In particular, K562 and SGC-7901 cells were found to be the most sensitive to the cytotoxic effects of this essential oil, with IC50 being 16.16 mg/mL and 38.76 mg/mL, respectively. Finally, the authors studied the in vitro antioxidant activity with different common methods such as DPPH antiradical activity, reducing power, and anti-hydroxyl radical activity, showing that the tested essential oil exerted a moderate antioxidant capacity. The chemical composition of the essential oil was again determined via GC-MS, allowing the identification of 51 compounds, with menthol (30.69%), menthone (14.51%), menthyl acetate (12.86%), and neomenthol (9.26%) accounting for more than 50% of the constituents occurring in the essential oil.Mint essential oils are also well-known for their antioxidant activity. Sun et al.  conducteCitrus is the largest genus of the Rutaceae family, including about 70 species. Citrus aurantium L. (common name: bitter orange), Citrus bergamia Risso & Poit. (which is a synonym of Citrus limon (L.) Osbeck (common name: bergamot)), Citrus paradisi Macfad. (common name: grapefruit) and Citrus limon (L.) Osbeck (common name: lemon) are the most common sources of essential oils. Therefore, this section will focus on the essential oils obtained from these species, which are widely under study for their broad spectrum physiological and pharmacological properties including antimicrobial, anti-inflammatory, analgesic, antiproliferative, antimicrobial, and antioxidant activities.C. bergamia essential oil and its main constituents . The antibacterial activity was tested against 42 strains of Mycoplasma hominis, two strains of Mycoplasma fermentans and a strain of Mycoplasma pneumoniae. The MIC values registered for the essential oil ranged from 0.5 to 1% (v/v), with linalool and limonene showing high activity, especially on M. pneumoniae . In the same year, Adukwu et al. [Citrus species (grapefruit and bergamot). The antimicrobial activity of the Citrus species essential oils was confirmed against S. aureus. Moreover, the authors found that grapefruit essential oil did not show any anti-biofilm activity, unlike other essential oils, such as that extracted from lemongrass (Cymbopogon flexuosus (Nees ex Steud.) W. Watson).As regards antimicrobial activity, Furneri et al.  publisheu et al.  studied C. aurantium leaf essential oil showed antimicrobial activity, too. In fact, the essential oils prepared from leaves collected in different seasons were found to exert high activity against some Gram-positive bacteria , and moderate activity against yeasts and fungi . Chemical analysis performed through GC-MS allowed the identification of 46 compounds, with the highest concentrations of linalool (43.2% to 65.97%), linalyl acetate (0.77% to 24.77%), and α-terpineol (9.29% to 12.12%) [C. aurantium. In addition, the antifungal activity of C. aurantium essential oil was investigated [ 12.12%) . Similar 12.12%)  and Amma 12.12%)  more recstigated .Citrus x limon essential oil has been widely studied for its chemical composition and antimicrobial activity. Hamdan et al. [p-menth-1-en-7-al (4.63%), β-pinene (6.35%), and nerol (4.42%) are the main substances occurring in leaf essential oil. The same research showed that lemon oil exerts good antimicrobial activity against Gram-positive and Gram-negative bacteria, and yeasts . In 2014, Settanni et al. [In recent years, n et al.  investigi et al.  studied Citrus limon oil, Mitoshi et al. [With regards to the anti-inflammatory activity of i et al.  assessedC. aurantium on a model which accurately reflects human gastric ulcer, involving male Wistar rats in which a gastric lesion was induced via acetic acid. The results showed that bitter orange oil significantly decreased the gastric lesion area by 76% compared to the control group, at an oral dose of 250 mg/kg/day for 14 consecutive days.The protective effect of this essential oil was confirmed by the same research group, which published a study on the effect of d-limonene  in the same gastric ulcer model system. The same treatment reported in their previous investigation induced an increase in cell proliferation and cyclooxygenase 2 expression in the gastric mucosa, as well as vascular endothelial growth factor (VEGF)-mediated blood vessel formation. In addition, the treatment caused the over-production of gastric mucus, which plays a role in increasing the gastric barrier. The authors concluded that, considering the low adverse and side effects of this essential oil, it could be considered a good candidate for gastric ulcer treatment [The anti-inflammatory activity of essential oils may be the basis of their protective activity against gut inflammation diseases. Polo et al.  studied reatment .C. aurantium oil, orally administered at a dose of 7.50 mg/kg for 14 consecutive days to experimental animals in a different model of gastric ulcer . Besides the capacity to decrease gastric and duodenal lesions and the production of mucus, β-myrcene was found to be able to increase mucosal lipid peroxidation  and antioxidant defenses , thus suggesting that oxidative stress plays an important role in the activity of β-myrcene.In 2014, Bonamin et al.  demonstrN-formyl-Met-Leu-Phe (at a concentration of 0.1 μM), which is a chemotactic peptide that reacts with membrane receptors stimulating ROS production, and phorbol myristate acetate (at a concentration of 0.1 ng/mL), which stimulates the intracellular protein kinase C. In addition, cells were grown in the presence of extracellular or intracellular Ca2+ chelators. The results showed that bergamot essential oil (0.1%) increased intracellular ROS production induced by N-formyl-Met-Leu-Phe, in presence of extracellular Ca2+, while reducing the effect of protein kinase C activator phorbol myristate acetate (at concentrations ranging from 0.03 to 0.1%). The authors concluded that the pro-inflammatory potential of the essential oil needs to be carefully considered for any future clinical applications.The influence of bergamot essential oil on in vitro oxidative stress was also studied by Cosentino et al. , which uCitrus x limon) fruit peels and leaves using different extraction methods . The essential oils exerted different antioxidant and radical scavenging activities in in vitro chemical assays , depending on the part of the fruit (peels or leaves) and the extraction technique. The essential oils were also submitted to chemical analysis by GC-MS, showing that the most abundant component was limonene (ranging from 14.08% to 59.64%), followed by γ-terpinene (ranging from 1.82% to 19.03%), and β-pinene (ranging from 3.24% to 17.10%). The authors showed that the monoterpene hydrocarbon fraction was positively correlated in all antioxidant assays, suggesting that this fraction could be considered partly responsible for the observed antioxidant activity.Different results have been achieved by Loizzo et al.  which stCitrus species have been investigated for their potential anticancer activity. In fact, in 2013, two studies were published on the cytotoxicity of bergamot oil on a human neuroblastoma cell line. In more detail, the first study by Celia et al. [v/v) lower than those registered for the essential oil (0.02%–0.04% v/v). The authors emphasized the potential role of new delivery systems in improving the cytotoxic activity of essential oils.Finally, essential oils from a et al.  investigRusso et al.  focused Eucalyptus essential oils”, “Mentha essential oil”, and “Citrus essential oil”. This database reported six completed studies on Eucalyptus essential oils , twice daily after brushing, induced a modified whole mouth gingival index (MGI) of 2, in comparison with a 5% hydroalcoholic mouth rinse  and Listerine Zero® mouth rinse (20 mL) twice daily after brushing. Three studies evaluated the influence of the consumption of a dietary supplement on respiratory tract diseases . Finally, one clinical trial studied the effect of ice pops to alleviate pregnancy related nausea and vomiting (morning sickness).As regards and 2016 . Four stCitrus essential oil, six clinical trials have been registered, with two completed studies carried out in 2009 and 2011 (Finally, with regard to and 2011 . Two stuAmong natural plant products, essential oils deserve particular attention because of their uses in many different traditional healing systems all over the world. In addition, currently, distillation of essential oils from plant organs is a highly reliable and affordable process.As regards their efficacy, a huge amount of preclinical studies have documented the biological activities of essential oils, also elucidating their mechanism of action and pharmacological targets. In particular, antimicrobial, antioxidant, anti-inflammatory and anticancer activities have been demonstrated in a number of cell and animal models. However, the paucity of in human studies, compared with the in vivo/in vitro ones, limits the potential of essential oils as effective and safe phytotherapeutic agents, though the efficacy of essential oils in oral healthcare is well documented . Therefo