Phytochemical and biological activities of some Iranian medicinal plants

Abstract Context Due to adverse effects of synthetic compounds, there is a growing interest in utilization of plant-derived natural products in the pharmaceutical and food industries. Iranian endemic medicinal plants widely used in traditional practice have attracted much attention as antibacterial and antioxidant agents. Objective This review attempts to compile the accessible scientific research pertained to phytochemical compounds, antibacterial and antioxidant effects of essential oils obtained from some of the most widely used and distributed medicinal plants in Iran. Methods This review has been compiled using references via reliable databases (Google Scholar, SID and Science Direct) from 2010 to 2020. This literature review was limited to references published in English and Persian languages. Results Based on studies heretofore carried out, essential oils isolated from mentioned medicinal plants exhibited strong antioxidant activity which is attributed to their main phytochemical compounds; thymol, carvacrol, p-cymene and γ-terpinene. In addition, the antibacterial activities of essential oils of most plant species from Apiaceae and Asteraceae families were more susceptible against Gram-positive bacteria; Staphylococcus aureus and Bacillus cereus than Gram-negative bacteria; however, essential oils of other studied plant species manifested similar behaviours against both Gram-positive and -negative bacteria. Conclusions As there is rich ethnobotanical knowledge behind Iranian endemic medicinal plants, further scientific research is required to prove their safety and efficacy. This review revealed that there are numerous valuable medicinal plants adoptable in food and pharmaceutical industries in the near future.


Introduction
Traditional or complementary medicine is an important and often underestimated segment of health services. Nevertheless, this kind of medicine is to date acknowledged, as preferred primary health care system in many rural communities, particularly due to its affordability and effectiveness. Moreover, not only does it have a long history of use in health maintenance and disease prevention, but also an effective remedy for chronic diseases. It is estimated that over 75% of globe population rely on traditional medicines to treat various diseases, viz., diarrhoea, malaria, stomach-ache, cough, bilharzia and dysentery (Ghasemi Pirbalouti et al. 2010a;Rakotoarivelo et al. 2011;Mahomoodally and Chintamunnee 2012;Pan et al. 2014;Arumugam et al. 2016). It is even estimated that almost 25% of modern and 60% of antitumor drugs be derived from natural products (Newman and Cragg 2012;Veeresham 2012;Iqbal et al. 2017). The popularity of plant usage in Traditional Iranian Medicine (Persian Medicine) goes back to Babylonian-Assyrian civilization era (Amirmohammadi et al. 2014;Buso et al. 2020).
In spite of modern medicine development, medicinal plants still play an important role in Iran as curatives for various health problems Buso et al. 2020). Iran with different climatic and geographical zones is a habitat to at least 2300 species having aromatic and medicinal properties, wherein 7.9% are endemic (Owfi and Safaian 2017;Sheibani et al. 2018;Karim et al. 2020). Almost all parts of these plants (e.g., leaves, flowers, stems, seeds, fruits and roots) (Najafi et al. 2010;Hariri et al. 2018) produce essential oils as secondary metabolites for varied purposes; plant defence against pests or pathogens, pollinator attraction and seed dispersers (Dhifi et al. 2016). Currently, essential oils are in high demand in pharmaceutical, cosmetic, sanitary and food industries, as well as agriculture due to flavour, fragrances and versatile biological properties like antimicrobial, anticancer and antioxidant (Kumar et al. 2018). These characteristics are accredited to the presence of a complex mixture of aromatic compounds; terpenes, phenolic and phenylpropanoid compounds (Bakkali et al. 2008;Dhifi et al. 2016).
Over the past few years, antimicrobial resistance has become one of the most serious international public health concerns that threatens the effective prevention and treatment of infections resulting from a wide range of pathogens, viz., bacteria, fungi and viruses (Avaei et al. 2015;Prestinaci et al. 2015). Additionally, reducing the popularity of synthetic compounds among consumers has caused a higher discovery of natural antimicrobial agents. Generally, the mechanism of essential oil inhibiting pathogens growth is associated with essential oil type and microbial strains tested (Pauli and Kubeczka 2010). Gram-positive bacteria are generally more susceptible to essential oils than Gram-negative bacteria (Borges et al. 2013(Borges et al. , 2014, because they are surrounded by an outer membrane which has a more complex and assisting penetration of hydrophobic compounds through it. In other words, minute antimicrobial agents can easily access the cell membrane of Gram-positive bacterial strains (Zinoviadou et al. 2009;Hyldgaard et al. 2012). Furthermore, Gram-positive bacteria may ease the infiltration of essential oils of hydrophobic compounds due to lipophilic ends of lipoteichoic acid present in the cell membrane (Cox et al. 2000). The antimicrobial activity of essential oils is commonly evaluated via minimum bactericidal concentration (MBC) or minimum inhibitory concentration (MIC) (Balouiri et al. 2016), and agar well diffusion (Rao et al. 2019).
In addition, we have noted a rise in research on the substitution of synthetic or artificial antioxidants with natural compounds since butylated hydroxyanisole and butylated hydroxytoluene (BHT) were suspected to induce carcinogenesis and liver toxicity (Caleja et al. 2017). Sequentially, adoption of essential oils as natural antioxidants in food and pharmaceutical industries has increased (Chrysargyris et al. 2020). These compounds shield human body against oxidative stress disrupt by maintaining the balance between free radicals and antioxidant defence system (Alfadda and Sallam 2012). Free radicals through oxidative stress are involved in several health disorders; cardiovascular, inflammatory, age-related diseases, cataracts and cancer (Poljsak et al. 2013). These free radicals are collectively termed reactive oxygen species (ROS) and reactive nitrogen species including highly reactive species; hydroxyl (OHÁ) and nitric oxide (NOÁ) radicals (Li et al. 2016). They are produced when our cells create energy from food and oxygen or are exposed to microbial infections, extensive exercise or pollutants/toxins, i.e., cigarette smoke, alcohol, ionizing/UV radiations, pesticides and ozone (Gilca et al. 2007). Excessive ROS generated under abiotic stress causes significant damage to biomolecules; lipids, proteins and deoxyribonucleic acid (Sharma et al. 2012) leading to different chronic diseases (Ighodaro and Akinloye 2018). The most common methods to investigate antioxidant efficacy of essential oils are ferric reducing antioxidant power (FRAP) (Benzie and Strain 1996), 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) (Bondet et al. 1997), b-carotene-linoleic acid (linoleate) (Miller 1971) and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays (Bertrand et al. 2005).
Several authors have reviewed the beneficial uses of essential oils (Amorati et al. 2013;Chouhan et al. 2017). Swamy et al. (2016) reviewed selected essential oils from different countries that have great antimicrobial properties. However, few comprehensive reviews have been published on phytochemical compounds and pharmaceutical effects of Iranian endemic plants. Therefore, this review aimed to focus on 23 medicinal plants native to Iran, which are widely distributed and used in Iranian traditional medicine and among locals. The entire data were classified in three tables; traditional uses (Table 1), antioxidant effects (Table 2) and antimicrobial potential (Table 3) of essential oils from the selected medicinal plants. All the available information was compiled via reliable electronic databases; 'Google Scholar', 'Science Direct' and 'SID' from 2010 to 2020 to provide a foundational knowledge guide for its subsequent research and utilization.
Bunium persicum (Boiss.) B. Fedtsch. (Apiaceae) B. persicum (Figure 1(A)) is traditionally used to improve digestion, besides a flavouring and carminative agent and to treat varied ailments, viz., toothache, stomach-ache and dyspnoea (Pezhmanmehr et al. 2009;Amiri et al. 2012). The essential oil of B. persicum exhibited significant antioxidant activity using DPPH and b-carotene-linoleic acid (Nickavar et al. 2014) methods in presence of major compounds: b-pinene, p-cymene, cumin aldehyde and c-terpinene. In previous studies, the antioxidant capacity of B. persicum essential oil isolated by two different methods: microwave (MAE) and hydro-distillation (HD) techniques were compared and no significant difference in the antioxidant activities was reported. Consequently, MAE method was recommended due to shorter extraction time and faster energy transfer (Mazidi et al. 2012;Majidi et al. 2020). The DPPH and ABTS radical scavenging assays results indicated that the antioxidant activity of Zataria multiflora Boiss. (Lamiaceae) essential oil was greater than B. persicum essential oil (Aminzare et al. 2017). The antimicrobial properties of B. persicum essential oil with the main chemical compounds: cumin aldehyde, c-terpinene, b-pinene and p-cymene against Listeria monocytogenes, as multidrug-resistant bacteria, have been confirmed (Sharafati Chaleshtori et al. 2018). Likewise, B. persicum essential oil inhibited the growth of Candida albicans, with considerable antibacterial potential against Staphylococcus aureus and Escherichia coli (Rustaie et al. 2016). Additionally, the synergistic antibacterial activity of B. persicum and Cuminum cyminum L. (Apiaceae) essential oils against Gram-positive bacteria (S. aureus, B. cereus and L. monocytogenes) has been recorded (Oroojalian et al. 2010).

Carum carvi L. (Apiaceae)
Caraway seeds (C. carvi) (Figure 1(B)) are used medicinally as a laxative, carminative, appetite stimulant, besides increasing lactation in pregnant women and alleviating menstrual pain (Haidari et al. 2011;Keshavarz et al. 2012). The in vitro antioxidant property of C. carvi essential oil measured by b-carotene bleaching and DPPH assays was reported by Fatemi et al. (2011). Moreover, other studies determined the antioxidant activity of C. carvi essential oil on liver and lung tissue changes histopathologically and indicated that C. carvi essential oil retained the balance via oxidants and antioxidants (Fatemi et al. 2010;Dadkhah et al. 2011Dadkhah et al. , 2018. In a study on antibacterial activity of caraway essential oil, the Gram-positive bacteria; Bacillus subtilis and S. aureus exhibited more sensitivity in relation to Gram-negative pathogens; E. coli and Pseudomonas aeruginosa (Sayhoon et al. 2013).

Chaerophyllum macropodum Boiss. (Apiaceae)
C. macropodum (Figure 1(C)) is distributed in Iran and Turkey, while other species are detectable in other areas particularly Europe and central Asia (Mozafarian 1996). This plant is not only used in traditional healing practices to treat cold and stomach, but also in culinary (Jahantab et al. 2018;Moazzami Farida et al. 2018). The antioxidant activity of essential oil from C. macropodum aerial parts was determined by DPPH radical scavenging and b-carotene bleaching tests. The results indicated that essential oil containing the most prominent bioactive compounds: trans-ocimene, cis-ocimene and c-terpinene possessed low antioxidant activity as compared to BHT (Haghi et al. 2010). Additionally, the chemical composition and antioxidant properties of C. macropodum essential oil isolated by HD and microwave-assisted hydrodistillation (MAHD) methods were measured and compared. The main constituents of both essential oils obtained by HD and MAHD, were (E, Z)-b-ocimene, myrcene and terpinolene, respectively. There was no significant difference in the antioxidant activity of both essential oils (Khajehie et al. 2017). Moreover, MIC concentrations of essential oils obtained from C. macropodum leaves and flowers were evaluated against 12 bacterial strains using the micro-well dilution assay. Thirty constituents were identified and their main classes were oxygenated, non-oxygenated monoterpenes and sesquiterpenes (trans-b-farnesene and trans-b-ocimene). Salmonella paratyphi-A serotype, Proteus vulgaris, Staphylococcus epidermidis and Klebsiella pneumonia were the most susceptible species with MIC ranging from 125 to 250 lg/mL (Ebrahimabadi et al. 2010). Khajehie et al. (2017) evaluated the antifungal activities of C. macropodum aerial parts essential oil through HD and MAHD techniques by MIC or minimum fungicidal concentrations (MFCs) methods and reported that MAHD had no adverse effects on inhibitory effects of the essential oil, besides    Rezayan and Ehsani (2015) Prangos ferulacea (L.) Lindl.
Leaves         (2017) The essential oils with highly inhibitory effects against Gram-positive bacteria are highlighted in grey.
Trichoderma harzianum was the most sensitive microorganism with MIC of 625 lg/mL.

Cuminum cyminum L. (Apiaceae)
C. cyminum (Figure 1(D)), or cumin seeds, is not only the main ingredient of different traditional cuisines, but also has been widely used to cure varied ailments; gastrointestinal diseases, tooth decay, cough, epilepsy, diabetes and aches (Gachkar et al. 2007;Johri 2011;Srinivasan 2018). The essential oil of C. cyminum seeds rich in b-pinene, c-terpinene-7-al and c-terpinene have considerable radical-scavenging and antioxidant activities that are comparable with Trolox and BHT (Fatemi et al. 2013). Likewise, Ladan Moghadam (2016), showed that the antioxidant activity of C. cyminum essential oil was even higher than trolox. Moreover, Zolfaghari et al. (2015), studied in vitro and in vivo antimicrobial potentiality of cumin seeds essential oil against Gram-positive and negative bacterial strains and revealed that B. cereus (MIC ¼ 2.07 ± 0.51 mg/mL) was the most species. Later, the combinations of C. cyminum essential oil and standard antibiotics (sodium benzoate) were screened to determine the presence of any synergistic activities. The results demonstrated that the antimicrobial activity of C. cyminum essential oil preservatives, when used in combination with other preservatives, was higher. Moreover, the Gram-positive bacteria (MIC ¼ 1.13 ± 0.11%) were more sensitive to C. cyminum essential oil than Gram-negative bacteria (MIC ¼ 1.93 ± 0.11%) (Ekhtelat et al. 2019). Similarly, Tavakoli et al. (2015) indicated good antimicrobial activity of C. cyminum essential oil combined with nisin (a preservative agent) against Salmonella typhimurium growth at 10 C and S. aureus growth at 10 C and 25 C, respectively, in BHI broth during study period of 43 days.

Ferulago angulata (Schltdl.) Boiss. (Apiaceae)
Chavil (F. angulata) (Figure 1(E)) has been traditionally used as an antiseptic, air freshener and spice in Iranian cuisine Bagherifar et al. 2019). The antioxidant capacity of F. angulata essential oil collected from diverse Iran provinces was compared. In DPPH assay, the strongest antioxidant effects were found in Chavil collected from Lorestan Province (IC 50 ¼11.70 ± 0.217 mg/mL) attributed to its main compounds of a-pinene and Z-b-ocimene (Shahbazi et al. 2016). Chavil essential oil (a-pinene and cis-b-ocimene) from the southwestern regions of Iran also presented an excellent antioxidant activity comparable with BHT (Ghasemi Pirbalouti et al. 2016). The phytochemical composition and antibacterial activity of F. angulata essential oil collected from different parts of Iran were assessed by agar dilution and disc diffusion methods. The results showed that the essential oil from F. angulata grown in Kurdestan Province containing high amount of a-pinene and Zb-ocimene exhibited highest antibacterial activity against all the tested bacteria particularly E. faecalis (MIC and MBC ¼ 33.3 and 40 lg/mL) (Shahbazi et al. 2016). Mumivand et al. (2019) reported that Gram-negative pathogens (E. coli and P. aeruginosa) were more resistant to essential oil of F. angulata aerial parts. Likewise, Moghaddam et al. (2018) studied the antibacterial and antifungal activities of essential oil from F. angulata seeds against six bacterial and fungal species and revealed that Bacillus thuringiensis, Fusarium oxysporum and Colletotrichum trichellum were sensitive to essential oil containing high content of cisb-ocimene, a-pinene and a-phellandrene. Similarly, the findings of Ghasemi Pirbalouti et al. (2016) indicated that Chavil essential oil extracted from F. angulata had very strong activity against L. monocytogenes (Gram-positive bacterium). Similarly, Shahbazi et al. (2015) reported that the two Gram-positive bacteria (L. monocytogenes and B. cereus) were more sensitive to F. angulata essential oil.

Heracleum persicum Desf. (Apiaceae)
Golpar (H. persicum) (Figure 1(F)) distributed in Alborz regions has been widely used in traditional medicine and food in different parts of Iran and Middle Eastern countries (Amin 1991;Kousha and Bayat 2012;Roshanaei et al. 2017). In traditional Iranian medicine, fruits and stems of this plant are used as a spice, in pickling (Shariatifar et al. 2017), and as an analgesic, antiseptic, anti-flatulence and digestive aid, as well as remedy for stomach pains and infections (Hemati et al. 2010;Bahadori et al. 2016). In the comparative antioxidant activities of 10 selected herbs via DPPH method, H. persicum extract did not show a significant result (Dehghan et al. 2016), contrastingly, comparative study on antioxidant activity of essential oils from four Heracleum species; H. pastinacifolium C. Koch and H. persicum essential oils showed the highest activities which could probably be due to the presence of myristicin and (E)-anethole (Firuzi et al. 2010). The data (Shariatifar et al. 2017) obtained from disc diffusion and broth micro-dilution methods demonstrated a notable antimicrobial activity of H. persicum essential oil against the selected bacterial strains; S. aureus Rezayan and Ehsani (2015) reported that the antibacterial effects of H. persicum essential oil with principal compounds; hexyl butanoate, octyl isobutyrate, octyl 2-methylbuyrate and pentylcyclopropane, were more significant on L. monocytogenes (PTCC 1165) as a Gram-positive bacterium. The highest antimicrobial potentials were reported for essential oil of H. persicum on B. subtilis (Noudeh et al. 2010). In a study by Ehsani et al. (2019) evaluated H. persicum essential oil, nisin and Lactobacillus acidophilus (as a probiotic agent) to inhibit the growth of L. monocytogenes and reported that a combined formulation containing low concentration of H. persicum essential oil, nisin and probiotic agent signified a synergistic effect.
Prangos ferulacea (L.) Lindl. (Apiaceae) P. ferulacea (Figure 1(G)) (Djashir) is used to flavour foods, for medical preparations, and animal fodder. In addition, Djashir is a laxative, wound healing, antihypertensive and carminative agent (Yousefi et al. 2017;Mottaghipisheh et al. 2020). Bazdar et al. (2018) evaluated the antioxidant potential of essential oil and extract from P. ferulacea flowers and leaves against DPPH radicals and reported that the hydro alcoholic flowers (IC 50 ¼8.01 ± 0.60) containing the highest number of flavonoids showed the highest antioxidant activities compared to Djashir essential oil (IC 50 ¼23.90 ± 2.59 and 22.99 ± 2.13, respectively). A comparative study ) assessed the effects of novel ohmic-assisted hydrodistillation (OAHD) on chemical compositions, besides antioxidant and antibacterial activities of essential oil from P. ferulacea leaves and demonstrated a significant difference in the percentage of chemical compositions percent between HD and OAHD, but antioxidant effects (IC 50 ¼488.14 and 570.52 lg/mL, respectively) were less remarkable than BHT (IC 50 ¼17.34 lg/mL). OAHD method influence on antibacterial efficacy of P. ferulacea essential oil, B. cereus, Listeria innocua, S. aureus, E. coli, S. typhimurium and Enterobacter aerogenes was studied. The essential oil extracted by HD constituting mainly (E)-b-ocimene, p-cymene, 2,3,6-trimethylbenzaldehyde, germacrene D and terpinolene showed better antimicrobial activity, particularly against S. aureus. These researchers also indicated that sonication prior to extraction had no significant efficacy on antibacterial effects and chemical compounds of P. ferulacea essential oils, and the most sensitive and resistant bacterial species were S. aureus and S. typhimurium, respectively. Therefore, the ultrasonic pre-treatment of plants prior to extraction could be desirable to minimize the extraction times (Seidi Damyeh and Niakousari 2016).

Achillea millefolium L. (Asteraceae)
A. millefolium (Boomadaran) (Figure 1(H)) is an herbaceous flowering plant with several traditional uses, viz., anti-infections, antihemorrhage, anti-inflammation and antidiabetic (Mirdeilami et al. 2011;Mazandarani et al. 2013;Bahmani et al. 2014). A. millefolium essential oil exhibited significantly greater radical scavenging activity (IC 50 ¼23.11 ± 0.04 mg/mL), than trolox (IC 50 ¼23.51 ± 0.05 mg/mL). b-Carotene bleaching method findings also confirmed its capacity (Sahari Moghadam et al. 2017). Additionally, A. millefolium, A. graveolens and Carum copticum L. (Apiaceae) essential oils were tested for in vitro antioxidant activity using DPPH, FRAP and b-carotene bleaching assays. The antioxidant activity of A. millefolium essential oil was statistically superior to other tested plants and even trolox. The presence of high levels of phenolic substances, viz., thymol and carvacrol may attribute to the antioxidant properties of A. millefolium essential oil (Kazemi 2015). Comparatively, the essential oil of A. millefolium leaves had weaker antimicrobial effects than the essential oil from its flowers positively correlating to occurrence of camphor, borneole and a-cadinol. The highest activity of essential oils was observed against S. aureus, Penicillium glaucum and S. cerevisiae (Ahmadi-Dastgerdi et al. 2017). is an important herb in the south of Kerman Province, Iran (Mozafarian 1996). In folk medicine, this plant was used for to treat skin disease and high blood pressure (Dolatkhahi et al. 2014). Jamzad (1996) demonstrated that A. kermanensis essential oil possessed considerable antioxidant and radical scavenging activities through DPPH and b-carotene-linoleic acid assays (Jamzad 1996

Dracocephalum kotschyi Boiss. (Lamiaceae)
D. kotschyi (Figure 1(J)) aerial parts are used in traditional medicine to treat stomach, headache, toothache and liver disorders (Heydari et al. 2019;Fallah et al. 2020). The chemical composition and antioxidant activity of D. kotschyi essential oil were analysed by DPPH and GC/MS methods, respectively. The results showed that the essential oil containing neral geranial, geranyl acetate and a-pinene had good antioxidant potential (Ashrafi et al. 2017;Fallah et al. 2020). The essential oils from cultivated and wild D. kotschyi were tested for their inhibitory effects against 12 microbial strains by MIC and MBC tests. This activity was more marked against Gram-positive bacteria, while, essential oil from the wild was the most effective to halt C. albicans growth, the essential oil from crops was more marked against Gram-positive bacteria (B. subtilis) (Ghavam et al. 2021). Ashrafi et al. (2017) reported that D. kotschyi essential oil showed the greatest bactericidal activities against the highly susceptible strains of most Gram-positive organisms (except E. faecalis) with MIC values of 80-160 lg/mL and a few Gramnegative organisms; Salmonella typhi, S. paratyphi and S. enterica (80-160 lg/mL). In a comparative study, the antimicrobial activities of D. polychaetum Bornm., D. kotschyi and D. multicaule Montbret & Aucher ex Benth. were investigated wherein D. kotschyi essential oil with MIC of 200 lg/mL exhibited the strongest antimicrobial activity against S. epidermidis (Khodaei et al. 2018). D. kotschyi essential oil inhibitory effects against K. pneumonia as the third leading cause of hospital-acquired pneumonia were reported which can be replaced with conventional antibiotics such as amoxicillin (Shakib et al. 2018). In an investigation, the chemical composition and antibacterial efficacy of D. kotschyi essential oil were isolated by three different techniques (HD, solvent-free microwave extraction (SFME) and MAHD). The lowest MICs (2 mg/mL) were of the essential oil extracted by MAHD and SFME against S. aureus. However, the maximal limonene compounds were found in the essential oil obtained by HD (Moridi Farimani et al. 2017).

Hymenocrater spp. (Lamiaceae)
H. longiflorus Benth. (Figure 1(K)) and H. calycinus (Boiss.) Benth. (Figure 1(L)) are termed Gol-e-Arvaneh in Persian (Morteza-Semnani et al. 2016). In Iranian traditional and folk medicine, it is optimally consumed for sedative, inflammation and skin antiallergenic (Asri et al. 2017). The antioxidant activities of essential oils besides polar and non-polar fractions of methanolic extract from H. longiflorus were estimated by DPPH and b-carotene-linoleic acid, respectively. According to DPPH assay results, polar extract exhibited better antioxidant activities due to lower EC 50 , while oxidation of linoleic acid was effectively inhibited by non-polar extracts (Ahmadi et al. 2010

Mentha piperita L. (Lamiaceae)
M. piperita (peppermint) (Figure 1(M)), a natural hybrid between spearmint (M. spicata L.) and water mint (M. aquatica L.) (Işcan et al. 2002), is traditionally used for migraine headache, antispasmodic, antiemetic, common cold symptoms, disinfectant and decongestant (Mikaili et al. 2012). Yazdani et al. (2019) demonstrated that M. piperita essential oil had a remarkable antioxidant effect comparable to BHT. According to b-carotene bleaching and DPPH radical tests, peppermint essential oil enriched with menthol and menthone displayed good antioxidant potential as compared with BHT and trolox ). The in vitro antimicrobial property assessments demonstrated that M. piperita essential oil was more effective on Gram-positive (S. epidermidis, B. subtilis and S. aureus) than Gram-negative bacteria (S. dysenteriae and K. pneumonia) (Yazdani et al. 2019). Saharkhiz et al. (2012) reported that peppermint essential oil inhibited the biofilm formation of C. albicans and C. dubliniensis at concentrations up to 2 mL/mL using a 2,3-bis(2-methoxy-4nitro-5-sulfo-phenyl)-2H-tetrazolium-5-carbox-anilide reduction assay. and Z. multiflora were tested for antimicrobial efficiency against oral bacteria; Streptococcus mutans, C. albicans and E. faecalis via broth micro-dilution method. The study revealed that O. sanctum, A. sieberi and S. mirzayanii essential oils rich in 1,8-cineole displayed strong antimicrobial effects (Zomorodian et al. 2015). Two years later, Zomorodian et al. (2017) investigated the antimicrobial effects of essential oil from S. mirzayanii leaves against some common pathogenic bacteria and fungi and found that Gram-negative (E. faecalis) bacteria were more sensitive than Gram-positive ones.

Satureja spp. (Lamiaceae)
About 16 Satureja species are grown in Iran, of which, S. bachtiarica (Figure 1(O)), S. khuzestanica (Figure 1(P)) and S. rechingeri Jamzad (Figure 1(Q)) can be easily found in different parts of Iran (Jamzad 1996;Razzaghi-Abyaneh et al. 2013). In Iranian folk medicine, they treat cramps, muscle pains, nausea indigestion, diarrhoea and infectious diseases (Senatore et al. 1998;Bezi c et al. 2009;Hadian et al. 2014). The aerial parts of these plants are used in traditional medicine as antibacterial, antiinflammation, analgesic, antiseptic besides flavouring agents (Naghibi et al. 2005;Ghasemi Pirbalouti et al. 2010b). Alizadeh (2015) evaluated the antioxidant activity of essential oil and extract from S. rechingeri using DPPH and FRAP assays and revealed that antioxidant capacity of S. rechingeri extract was stronger than its essential oil due to high concentration of phenolic contents. Similarly, antioxidant activity of S. rechingeri essential oil solely and in combination with deuterium depleted water (DDW) has been evaluated using glutathione S-transferase (GST), lipid peroxidation (LP) and glutathione (GSH) methods respectively and based on data, essential oil solely or in combination with DDW showed a high antioxidant activity level as compared to BHT (Attaran et al. 2015;Rasooli et al. 2016). The therapeutic effects of DDW on various diseases in humans mainly cancer have been previously confirmed due to its great antioxidant potentials (Basov et al. 2019). Memarzadeh et al. (2020) characterized the impact of different extraction techniques vs. HD and microwave-assisted steam hydro-diffusion (MSHD) on phytochemical analysis and antioxidant capacity of S. bachtiarica essential oil. Although there was an equal amount of two principal components (carvacrol and thymol) present in the essential oils extracted by both methods, the antioxidant activity of essential oil extracted by MSHD was higher than that of HD. A comparative study assessed the chemical compositions and antioxidant activities of four essential oils (S. khuzestanica, Oliveria decumbens Vent. (Apiaceae) and Thymus daenensis Celak. (Lamiaceae) and their components).
The results showed that antioxidant activity of S. khuzestanica essential oil was weaker than other tested essential oils (Saidi 2014). S. khuzestanica essential oil (IC 50 ¼28.71 lg/mL) exhibited the highest DPPH scavenging activity and strong antioxidant activity in b-carotene-linoleic acid assay (Saei-Dehkordi et al. 2012). Alizadeh (2015) assessed the antimicrobial effects of S. rechingeri oil against four microorganisms: C. albicans (ATCC 10231), S. aureus (ATCC 6538), S. epidermidis (ATCC 1435) and E. coli (ATCC 25922) by recording inhibition zones and MIC and revealed that S. rechingeri essential oil had a significant potential to inactivate the growth of all tested pathogens (MIC ¼ 0.19 and 0.39 lL/mL) compared to standard antibiotics (tetracycline and amoxicillin). The in vitro antibacterial activities of S. bachtiarica essential oil were also evaluated against several bacterial species. The results indicated that S. bachtiarica essential oil containing carvacrol and thymol showed a stronger antimicrobial activity against S. typhimurium and L. monocytogenes (Ghasemi Pirbalouti et al. 2017). The inhibitory effect of S. bachtiarica essential oil against P. aeruginosa was also reported (Ghasemi Pirbalouti and Dadfar 2013). The antibacterial efficacy from S. bachtiarica and T. daenensis essential oils against S. aureus was considerably higher than that from Dracocephalum multicaule Montbr. & Auch. (Lamiaceae) and Tanacetum polycephalum Schultz-Bip (Asteraceae) essential oils (Ghasemi Pirbalouti et al. 2014). Previous researches demonstrated that S. bachtiarica essential oil had a therapeutic potentiality to treat Helicobacter pylori and L. monocytogenes (Falsafi et al. 2015;Fathi-moghaddam et al. 2020). The antibacterial activity of essential oils from Satureja species against some Gram-positive and negative bacteria was evaluated by disc diffusion method. The strongest antibacterial activities were observed in S. khuzistanica and S. rechingeri essential oils against B. cereus with MIC of 0.25 mg/mL. Interestingly, the ability of whole essential oils to prevent tested pathogens except P. aeruginosa was comparable to, or in most cases greater than, those of their pure main constituents (Hadian et al. 2012). Similarly, both S. khuzistanica and S. rechingeri essential oils possessed stronger antibacterial potential against Gram negative bacteria (E. coli and S. flexneri) than S. bachtiarica ). S. khuzestanica essential oil showed strong antibacterial activity against S. aureus which was mainly correlated to presence of carvacrol (Rashidipour et al. 2016). Mahboubi and Kazempour (2016) evaluated in vitro antibacterial activity of S. khuzestanica essential oil, carvacrol and gentamicin and their synergistic effect on E. coli. They found that antibacterial activity of carvacrol was higher than essential oil. They also reported a considerable synergistic effect while using gentamicin with carvacrol and S. khuzestanica essential oil. Likewise, Hashemi and Khodaei (2020) conducted an in vitro study to assess the inhibitory potential of S. khuzestanica and S. bachtiarica essential oils solely or in combination against Lactobacillus plantarum LU5 growth as a probiotic culture or S. flexneri, and E. coli. Their results confirmed that the mixture of both essential oils had no synergistic effect on probiotics while it significantly prohibited the pathogen. The antibacterial effects of S. khuzestanica essential oil alone and in combination with both synthetic (ciprofloxacin fluconazole and amphotericin B) and natural (lysozyme) agents using fractional inhibitory concentration indices and MIC assays were studied against food-borne microorganisms. The results indicated that the interactive effects of combinations between essential oil and ciprofloxacin against E. coli and S. typhimurium were considerable (Saei-Dehkordi et al. 2012). Likewise, Golparvar et al. (2018) reported that essential oils of S. hortensis L. and S. khuzestanica showed antimicrobial activity against S. aureus and C. albicans (MIC ¼ 0.1, 0.2 and 0.5 lL/mL, respectively).

Thymus spp. (Lamiaceae)
Thymus contains 18 species in Iran, wherein T. daenensis ( Figure  1(R)) and T. kotschyanus Boiss. & Hohen. (Figure 1(S)) are widely distributed in the central and southern parts of Iran (Jalas 1982;Mozafarian 1996). They treat common cold, high blood pressure, vomiting, heartburn, asthma and cough (Naghibi et al. 2005;Rahimmalek et al. 2009;Emami Bistgani and Sefidkon 2019). The antioxidant activities of Thymus species including T. kotschyanus, T. daenensis and T. eriocalyx Jalas have been addressed by various model systems; DPPH and b-carotene/linoleic acid. Their main phytochemical compositions were thymol, carvacrol and c-terpinene. While the antioxidant effect of T. daenensis essential oil was higher than the other essential oils in DPPH assay and T. eriocalyx Jalas. exerted the greatest antioxidant activity in b-carotene/linoleic acid test  and even greater than that of reference antioxidant (Alavi et al. 2010). In another comparative study, T. vulgaris L. exhibited the highest antioxidant activity as compared to other Thymus species (T. daenensis and T. kotschyanus) due to high thymol constituent (Mehran et al. 2016). However, the activity of T. kotschyanus leaves essential oil was lower than the positive control (BHT) (Shafaghat and Shafaghatlonba 2011). T. kotschyanus essential oil exerted notable antimicrobial effects on C. albicans and B. cereus (Ahmadi et al. 2015). Golkar et al. (2020) compared the antibacterial activities and chemical compositions of Thymus species and Z. multiflora through disk diffusion and broth microdilution assays against both Gram-positive and negative bacteria. They reported that T. kotschyanus and Z. multiflora had considerable antibacterial effects (MIC ¼ 20 lg/mL) which might be attributed to high thymol and carvacrol levels. The antifungal activities and phytochemical compounds of T. daenensis essential oil were tested against two fungi. GC/MS analysis identified the major components: thymol, carvacrol and p-cymene, as well as the potent inhibitory effects at very broad spectrum against A. fumigatus, A. niger and C. albicans (Hadipanah and Khorami 2016; Mohammadi Gholami et al. 2018). Asbaghian et al. (2011)

Zataria multiflora Boiss. (Lamiaceae)
Z. multiflora (Figure 1(T)), (Avishan-e-Shirazi), has been used for many decades as a flavouring ingredient in a number of Iranian cuisines (Gandomi et al. 2009;Basti et al. 2016). It has several traditional uses as an infusion, decoction or vapour to treat digestive problems, headache, common cold, migraine and bone pain (Safa et al. 2013;Nasab and Khosravi 2014). Z. multiflora essential oil containing the phenolic compounds particularly carvacrol and thymol demonstrated a high antioxidant activity through b-carotene-linoleic acid and DPPH assays (Fatemi et al. 2012;Dini et al. 2015), but lower than BHT (Hashemi et al. 2011). A number of different methods have been used to compare the radical-scavenging/antioxidant activity of essential oils isolated from Z. multiflora leaves and Ferula assa-foetida L. latex. The free radical scavenging activity estimated by inhibitory concentration ranged from 2.46 ± 0.75 to 4.58 ± 1.4 mg/mL for Z. multiflora which was more susceptible than that of F. assa-foetida essential oil (Kavoosi and Purfard 2013). The other related study results indicated that use of Z. multiflora essential oil could considerably modulate antioxidant/oxidative stress parameters including LP and GSH, as well as antioxidant enzymes such as GST Attaran et al. 2018). In a study by Sharififar et al. (2011), Z. multiflora essential oil exhibited strong scavenging activity, inhibiting LP at all tested doses (100, 200 and 400 mL/kg/day). Previously, several studies proved the antibacterial activities of Z. multiflora essential oil against different bacterial species.  assessed the antibacterial potency of Z. multiflora essential oil (100 and 200 mg/kg b.w.) using disc diffusion, agar well diffusion, besides MIC and MBC determination assays as well as caecal ligation and puncture model. They reported that S. aureus and B. cereus (Gram-positive bacteria) were more sensitive to Z. multiflora essential oil than E. coli and P. aeruginosa (Gram-negative bacteria). Likewise, Rahimi et al. (2019) indicated that Z. multiflora essential oil inhibited A. flavus growth at 50-400 ppm concentrations. Even, Mahboubi et al. (2017) evaluated the antimicrobial activity of Z. multiflora essential oil and its main compounds; thymol, carvacrol and p-cymene against P. aeruginosa. The MICs results showed the equal growth inhibitory effects of both essential oil and its major compositions. The antimicrobial activity of Z. multiflora essential oil collected from Khorasan Province was analysed against seven microorganism strains. The lowest MICs were against P. aeruginosa (25 lg/mL) and P. vulgaris (25 lg/mL) and S. cerevisiae, P. digitatum and A. niger were the most resistant microorganisms (Avaei et al. 2015). A comparative study on antibacterial activities of different essential oils against Lactococcus garvieae, as the causative agent of lactococcosis, indicated that the inhibitory effect of Z. multiflora essential oil (MIC ¼ 7.8 lg/mL) were far stronger than  (Mahmoodi et al. 2012). Similarly, the antibacterial property of Z. multiflora essential oil was superior to Berberis vulgaris L. (Berberidaceae) extract (Langroodi et al. 2018). Recently, Mahammadi Purfard and Kavoosi (2012) compared the effect of Z. multiflora essential oil and aqueous extract on inhibition of P. aeruginosa, S. typhi, E. coli, K. pneumoniae, S. aureus, S. epidermidis, B. subtilis, A. niger and C. albicans and demonstrated that Z. multiflora essential oil significantly inhibited the growth of all tested pathogens except P. aeruginosa, while, Z. multiflora extract was unable to inhibit the growth of all tested pathogens. Furthermore, the synergistic antibacterial activity of Z. multiflora essential oil in combination with monolaurin as a non-traditional antimicrobial agent was investigated. Consequently, the combination of these components revealed a more potent inhibitor against L. monocytogenes (Raeisi et al. 2016). In addition, the antibacterial property of Z. multiflora essential oil in combination with other antimicrobials has been well investigated. Rahnama et al. (2012) reported the enhanced synergistic antibacterial effect of Z. multiflora essential oil and nisin on L. monocytogenes through decrease in MIC and MBC values. Likewise, Javan (2016) indicated that the combination of Z. multiflora and Trachyspermum ammi L. (Apiaceae) essential oils exhibited a synergistic effect on the bacterial inhibition, and B. cereus was the most sensitive pathogen. For the first time, the application of silver nanoparticles as an antimicrobial agent in combination with Z. multiflora essential oil against a variety of pathogens S. aureus, methicillin-resistant S. aureus (MRSA), S. epidermidis and P. aeruginosa was investigated by Sheikholeslami et al. (2016). They confirmed that these compounds exerted additive effects against S. epidermidis and S. aureus. Moreover, Nasseri et al. (2016) demonstrated that Z. multiflora essential oil loaded with nanoliposomes showed higher antifungal effect on Aspergillus spp., Rhizoctonia solani and Rhizopus stolonifer than non-capsulated essential oil. Khatibi et al. (2017) also reported a significant increase in inhibitory effect of Z. multiflora essential oil against E. coli O157:H7 after encapsulation into nanoliposomes. Moreover, Shahabi et al. (2017) reported that although conversion of Z. multiflora essential oil to nanoemulsion could not significantly improve its antibacterial activity, but it enhanced its antibiofilm activity.

Ziziphora clinopodioides Lam. (Lamiaceae)
In Iranian folklore, different parts of kakuti-e kuhi (Z. clinopodioides) (Figure 1(V)), i.e., from leaves to roots were commonly used as spice and treatment of digestive system, cold and toothache (Asgharipour et al. 2016;Amiri et al. 2019). In the present study, antioxidant compounds (total phenol and flavonoid contents) and antioxidant activities of Z. tenuior L. and Z. clinopodioides essential oils were compared. The antioxidant analysis revealed that both essential oils considerably reduced the value of DPPH free radicals. The total phenolic compounds content in Z. clinopodioides essential oil (49 ± 1.4 mg quercetin/100 g oil) was higher than Z. tenuior essential oil (30.3 ± 0.1 mg gallic acid/ 100 g oil) (Hazrati et al. 2020). Shahbazi (2017) determined antioxidant activity of Z. clinopodioides essential oil was determined by four different tests; TBA and FRAP assays and revealed that the antioxidant effects of essential oils harvested from Kermanshah Province were highest. Z. clinopodioides essential oil exhibited a considerable antibacterial activity against food-borne pathogens, with MIC and MBC values ranging from 0.0012 to 0.0025 lL/mL, respectively, even much higher than records of tetracycline as a positive control, 2-2.5 lL/mL. Generally, Gramnegative bacteria are more resistant than Gram-positive ones (Shahbazi 2015). An in vitro study evaluated the antifungal properties of C. cyminum, Z. clinopodioides and Nigella sativa L.
(Ranunculaceae) essential oils on Aspergillus parasiticus, which is able to produce aflatoxin as a toxic and carcinogenic metabolite. The findings from broth microdilution method, revealed that the tested fungi were most sensitive to C. cyminum (MIC 90 ¼1.6 mg/ mL; MFC ¼ 3.5 mg/mL) and Z. clinopodioides (MIC 90 ¼2.1 mg/ mL; MFC ¼ 5.5 mg/mL) (Khosravi et al. 2011). Furthermore, the comparative study on compositions and antibacterial activity of essential oils from leaf, flower and stem of Z. clinopodioides collected from four natural habitats in the western provinces of Iran was conducted. No significant difference was observed in antibacterial potential of essential oils isolated from different parts of the plant. The Gram-negative bacteria (S. typhimurium and E. coli) were more resistance to Gram-positive bacteria (S. aureus, B. cereus, B. subtilis and L. monocytogenes) in relation to essential oils. The main constituent of all essential oils except the essential oils collected from Kurdestan was carvacrol (Shahbazi 2017).

Rosa damascene P. Mill. (Rosaceae)
Damask (R. damascena) (Figure 1(W)) is a hybrid between R. gallica L. and R. phoenicia Boiss. and was brought to European countries from Iran (Mahboubi 2016). This plant is widely used in varied industries; cosmetic, pharmaceutical and food for centuries (Georgiev and Stoyanova 2006). R. damascena essential oil exhibited a strong antioxidant activity as compared to BHT and trolox (Dadkhah et al. 2019;Kheirkhahan et al. 2020). Fatemi et al. (2020) revealed the positive treatment of animals with synergetic antioxidant effects of R. damascena essential oil and DDW due to regulation of oxidative stress/antioxidant parameters mainly; GSH, LP, GST and FRAP. Moreover, Afsari Sardari et al. (2019) showed that essential oil of fresh flowers had more antioxidant activity as compared to the spent flower essential oil. Damask essential oil exhibited antimicrobial activity against 20 microorganisms selected from both Gram-negative and positive bacteria. The essential oil exhibited the highest antimicrobial activity against P. vulgaris and K. pneumonia (Mahboubi et al. 2011). In a study, R. damascena essential oil with high alcoholic monoterpenes content; b-citronellol, geraniol, farnesol and geranyl acetate had the best antifungal and antibacterial effects . Kheirkhahan et al. (2020) studied antibacterial effect of R. damascena essential oil using the disc diffusion method against S. aureus, E. coli and S. typhi bacterial strains and reported that volatile oil obtained from Damask was effective against the three tested bacteria with MICs ranging from 500 to 1000 lL/mL.

Conclusions and future perspectives
This review discussed the antioxidant and antimicrobial potencies of essential oils of some indigenous plant species from Iran commonly used in Iranian traditional medicine for a wide range of applications (Table 1). The 23 studied essential oils showed high antioxidant activity particularly, C. carvi, C. cyminum, A. millefolium and T. daenensis essential oils which exerted even greater effects than synthetic antioxidants; Trolox and BHT ( Table 2). The antioxidant activity of these essential oils is related to their main chemical composition; primarily to the presence of polyphenolic compounds (carvacrol and thymol). These natural antioxidants could be effectually used as an adjuvant to shield our body against oxidative stress-related disorders including cardiovascular diseases, dementia, neurodegenerative diseases and cancer. However, it mandates a detailed study to explore their efficacy, safety and exact mechanism in vivo and in clinical trials.
Furthermore, this review revealed that essential oils isolated from the selected endemic medicinal plants possessed strong antibacterial activities against various bacterial and fungal pathogens. As depicted in Table 3, Gram-positive bacteria; Staphylococcus spp., Bacillus spp. and Listeria monocytogenes are more sensitive to C. carvi, C. macropodum, C. cyminum, P. ferulacea, A. millefolium, Hymenocrater spp., Z. majdae and Z. clinopodioides essential oils than Gram-negative bacteria such as E. coli and S. enterica. Likewise, the other essential oils have similar effects on inhibition of both Gram-negative and positive bacteria. Therefore, it can be safely concluded that antimicrobial activity of essential oils is highly dependent upon some parameters mainly essential oil type and microbial strains tested. Perhaps, the difference in antimicrobial potential of these plant species might stem from varying their phytochemical compounds. In addition, future studies should be focussed to determine antimicrobial activity mechanisms of these pure essential oils and their individual major compounds as well as activity enhancement in combination with other antimicrobial agents.
Unfortunately, the commercial use of these essential oils as antimicrobials is still a challenging scenario because of their poor solubility and stability. Moreover, the antimicrobial effects of essential oil can be reduced via exposure to light, heat and oxidation (Khatibi et al. 2017). Nevertheless, encapsulation of essential oils and their constituents seems to be an efficient solution to overcome such problems due to improvement in their oxidativestability, thermo-stability, photo-stability, shelf-life and even biological activity as well as increasing their solubility (Stevanovic et al. 2020). Encapsulated Z. multiflora essential oil mentioned in this review is a good example. Thus, it is expected that this review would be helpful to adopt more efficient natural antimicrobial and antioxidant agents for pharmaceutical and food purposes.

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