Phytochemistry and Biological Properties of <i>Salvia verbenaca</i> L.: A Comprehensive Review

Mrabti, Hanae Naceiri; El Menyiy, Naoual; Charfi, Saoulajan; Saber, Mohammed; Bakrim, Saad; Alyamani, Reema A.; Rauf, Abdur; Ali, Ahmed M. H.; Abdallah, Emad M.; El Omari, Naserddine; Bouyahya, Abdelhakim; Assaggaf, Hamza

doi:https://doi.org/10.1155/2022/3787818

BioMed Research International

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Review Article | Open Access

Volume 2022 | Article ID 3787818 | https://doi.org/10.1155/2022/3787818

Phytochemistry and Biological Properties of Salvia verbenaca L.: A Comprehensive Review

Hanae Naceiri Mrabti,¹Naoual El Menyiy,²Saoulajan Charfi,³Mohammed Saber,⁴Saad Bakrim,⁵Reema A. Alyamani,⁶Abdur Rauf,⁷Ahmed M. H. Ali,^8,9Emad M. Abdallah,⁹Naserddine El Omari,¹⁰Abdelhakim Bouyahya,¹¹and Hamza Assaggaf¹²

Academic Editor: Dorota Formanowicz

Received04 Feb 2022

Accepted10 May 2022

Published24 May 2022

Abstract

The family Lamiaceae contains several plants used in traditional medicine to fight against different diseases. Salvia verbenaca L. (S. verbenaca) is one of the Lamiaceae species distributed around the Mediterranean regions. This plant exhibits different bioactive properties, including antibacterial, anticancer, antioxidant, antileishmanial, antidiabetic, immunomodulatory, and wound healing. This review was conducted to revise previous studies on S. verbenaca addressing its botanical description, geographical distribution, and phytochemical, pharmacological, and toxicological properties. Moreover, the main pharmacological actions of S. verbenaca major compounds were well investigated. Literature reports have revealed that S. verbenaca possesses a pivotal role in medicinal applications. The findings of this work noted that S. verbenaca was found to be rich in chemical compound classes such as terpenoids, phenolics, fatty acids, sterols, and flavonoids. Numerous studies have found that S. verbenaca essential oils and extracts have a wide range of biological effects. These results support the potential pharmacological properties of S. verbenaca and its traditional uses. This analysis can constitute a scientific basis for further refined studies on its pure secondary metabolites. Therefore, the outcome of the present work may support the perspective of identifying new therapeutical applications with detailed pharmacological mechanisms of S. verbenaca to prevent the development of some diseases such as neurodegenerative disorders. However, toxicological investigations into S. verbenaca are needed to assess any potential toxicity before it can be further used in clinical studies.

1. Introduction

Since the beginning of time, medicinal plants have been and continue to be the primary source of medicine [1]. Salvia verbenaca L. (S. verbenaca) is a medicinal herb belonging to the family Lamiaceae, which is the most representative genus of Salvia [2, 3]. This plant is endemic to the Mediterranean region, including Morocco, Canaries Islands, Algeria, Tunisia, Libya, Egypt, and Cyprus, and has also spread to Europe and Asia [4]. In traditional medicines, S. verbenaca has been used to fight against numerous diseases; several ancient and current investigations revealed that S. verbenaca presents a chemical diversity in terms of chemical composition according to the chemical characteristics of the extracts from various parts. Indeed, S. verbenaca contains numerous secondary metabolites that belong to a wide variety of phytochemical classes [5]. S. verbenaca terpenoids have been revealed to have a large diversity due to several factors, including genetic, ecological, environmental, edaphic, and diverse plant parts [6]. An antibacterial potential against a wide range of gram-positive and gram-negative bacteria has been documented [7–11]. Consequently, the antibacterial efficacy of extracts and essential oils (EO) from S. verbenaca was remarkable against gram-positive bacteria compared to the gram-negative bacteria. Furthermore, S. verbenaca was found to have an antioxidant effect against free radical damage [12] and significantly reduce the level of intracellular reactive oxygen species (ROS) [13, 14]. According to previous studies, the anticancer properties of S. verbenaca extracts and essential oils have also been reported [15–19]. The antiparasitic properties of S. verbenaca, in particular, antileishmanial effects, have been investigated elsewhere [20].

Besides, S. verbenaca was reported to have an inhibitory effect of xanthine oxidase [21] and a healing effect on burns [22]. Furthermore, S. verbenaca revealed immunomodulatory effects [23]. Furthermore, the toxicological tests found that the ethanolic extract of S. verbenaca did not cause any toxic symptoms or death in rats [24].

The objective of the current article was to provide a general review of S. verbenaca such as botanical description, geographical distribution, phytochemistry, and pharmacological properties. Hopefully, this analysis could be a scientific basis for further refined studies on pure compounds from S. verbenaca that may lead to the identification of new therapeutical applications.

2. Research Methodology

All data about S. verbenaca (botanical description, taxonomy, destruction, phytochemical, and pharmacological properties) were collected using several databases like Web of Science, Google Scholar, Scopus, ScienceDirect, SpringerLink, Wiley Online, PubMed, and SciFinder and were reviewed in order to compile literature on S. verbenaca. The structures of the chemical profiles were identified in S. verbenaca, and the ChemDraw Pro 8.0 software was used to create the illustrations.

2.1. Botanical Description

S. verbenaca is a perennial herb that reaches between 10 and 50 cm (in height), hairy at the top, odorous, more or less glandular at the top. It grows in the dry lawns, the slopes, and at the edges of the paths. The slightly branched stems carry bunches of dark blue flowers in spring. Leaves are oblong, 2-3 cm broad, crenelated or incised-lobed, with the upper stalkless (Figure 1). The flowers are quite small, pale blue or whitish, in whorls usually close together, forming a fairly short cluster; the fruiting calyx with almost closed lips, bristling with spread hairs; the corolla is 10–15 mm, twice as long as the calyx, with wide lips, very uneven, the upper one compressed and curved in a false shape, and the style with little or prominent point [25].

(a)

(b)

(c)

2.2. Geographic Distribution

S. verbenaca has a very wide geographical distribution around the Mediterranean region, including Morocco, Algeria, Tunisia, Canaries, Egypt, Libya, Turkey, Cyprus, Transcaucasia, and Western and Southern Europe. It is also grown in South West Africa, North America, and Australia [5].

2.3. Ethnomedicinal Uses

The ethnobotanical investigations into S. verbenaca revealed its wide applications in folkloric medicine to treat numerous disorders as listed in Table 1. In Morocco, its application in folk medicinal systems includes the treatment of some digestive disorders such as abdominal colics [26–28]. The most commonly used part of the plant is the aerial part, which is prepared by infusion before being used to treat respiratory problems and genitourinary and skin diseases [27]. Dried leaves are also used for the treatment of wounds, burns, and abscesses [29]. Aerial parts are utilized in decoction or infusion to treat diabetes [30].

2.4. Phytochemistry

Like all medicinal plants belonging to the family Lamiaceae, S. verbenaca contains numerous secondary metabolites with different classes, such as flavonoids, terpenoids, alkaloids, and phenolic acids. Currently, several analytical investigations using different technical tools (GC, GC-SM, GC-MS, GC-FID, HPLC, 1D and 2D NMR, IR, UV, 1H NMR, and 13C NMR) have been applied to identify and isolate bioactive compounds from medicinal plants. Indeed, investigations into the chemical constituents of S. verbenaca revealed the presence of terpenoids, phenolics, fatty acids, flavonoids, and sterols (Table 2). As listed in Table 2, the chemical content of S. verbenaca was investigated in different areas with various medicinal applications by using different analytical tools. The results are different according to numerous factors, such as the study area, plant part used, and adopted methodology.

The terpenoids contained in the essential oils of S. verbenaca L. mostly consist of α-pinene, β-pinene, sabinene, 1,8-cineole, β-phellandrene, linalool, p-cymene, linalyl acetate, E-β-ocimene, (Z)-β-ocimene, tricyclene, camphor, 1,10-di-epi-cubenol, epi-13-manool, cis-muurola-3,5-diene, δ-selinene, trans-sabinene hydrate acetate, β-caryophyllene, viridiflorol, and germacrene D [31–33] (Table 1, Figure 2).

Belloum et al. [36] evaluated the volatile contents of the essential oil of S. verbenaca aerial parts using GC-MS and GC. In this sense, they recorded the presence of many terpenoids like germacrene D (20.5%), β-phellandrene (3.8%), α-copaene (10.4%), β-caryophyllene (3.8%), epi-α-cadinol (11.6%), and 1,10-di-epi-cubenol (20.9%). These compounds were the major terpenoids identified in S. verbenaca L. as reported elsewhere [31]. Moreover, in Spain, Taârit et al. [34] identified camphor (38.94%), 13-epi-manool (5.61%), and caryophyllene oxide (7.28%), from the essential oils of its seeds. A Greek study on S. verbenaca aerial parts has identified (E)-caryophyllene (16.1%) and β-phellandrene (30.3%) [34]. Moreover, Khemkham et al. [35] revealed cis-muurola-3,5 diene (14.6%) in the dried aerial parts of S. verbenaca as a major compound.

Al-Jaber et al. [25] compared the different parts of S. verbenaca volatile compounds collected from two locations in Jordan. Monoterpene hydrocarbons dominated the emission profile of stem, sepal, and leaf samples from the Mediterranean zone (68.0%, 33.7%, and 42.2%, respectively). Oxygenated monoterpenes controlled the production and emission of flowering components, including preflowering buds, fully grown flowers, and petals. Also, Taârit et al. [33] showed that the major compounds in EOs in Salvia aerial parts from the three Algerian regions were the monoterpene hydrocarbons and oxygenated sesquiterpenes. Additionally, the influence of collecting locations and phenophases on the production and chemical composition of S. verbenaca L. essential oils was examined by Farhat et al. [6]. In this study, it was reported that at the floral stage, monoterpene hydrocarbons (31.9%) prevail, whereas oxygenated sesquiterpenes (27.5%) predominate at the early fruiting stage. Sesquiterpene hydrocarbons were the most abundant chemical class at late fruiting (28.2%). Furthermore, Al-Jaber [32] reported that S. verbenaca EO was primarily composed of oxygenated monoterpenes (61.32%), with the monoterpene alcohol linalool serving as the sole monoterpene alcohol, whereas the essential oil obtained from the air-dried plant was primarily composed of sesquiterpene hydrocarbons (62.66%), with germacrene D serving as the major component (25.92%). Chemical heterogeneity of EOs was isolated from three distinct S. verbenaca tissues (leaves, twigs, and stem). In this regard, the EO of S. verbenaca from the fruits contains the highest concentrations of -caryophyllene (23.1%) and caryophyllene oxide (15.9%), while the EO from the stems contains the highest concentrations of camphor and viridiflorol and, and in comparison, the leaf oil contains the highest concentrations of epi-13-manool and manool [33].

Regarding phenolic acid compounds, several phenolic compounds were identified in the S. verbenaca methanolic extract, which was the phenolic acid with six compounds: p-hydroxybenzoic acid, vanillic acid, rosmarinic acid, p-coumaric acid, caffeic acid, phenolic diterpenes, and ferulic acid, with three compounds: carnosol, carnosic acid, and methyl carnosate [6] (Table 1, Figure 3). In Turkey, Tepe et al. [38] extracted rosmarinic acid from the dried methanolic extracts of this plant.

Moreover, Farhat et al. [6] have identified several flavonoids in methanol extract from aerial parts of Tunisian S. verbenaca L such as luteolin, apigenin, genkwanin, cirsiliol, naringenin, hesperidin, and naringin (Table 1, Figure 4).

Certain fatty acids were found in S. verbenaca (Table 1). Taârit et al. [33] identified approximately eight constituents (oleic acid, linoleic acid, arachidic acid, linolenic acid, palmitic acid, stearic acid, palmitoleic acid, and ethyl palmitate) (Figure 5). Russo et al. [19] isolated several interesting fatty acids from essential oils of S. verbenaca aerial parts, including (Z)-9-octadecenoic acid (oleic acid), hexadecanoic acid (palmitic acid), methyl hexadecanoate (methyl palmitate), and ethyl hexadecanoate (ethyl palmitate).

Additionally, Kabouche et al. [40] on the roots of S. verbenaca allowed the isolation of other secondary metabolites including five sterols (campesterol, stigmasterol, sitosterol, 6-hydroxysalvonolone, and microstegiol) and two diterpenes (6,7-dehydroroyleanone, cryptanol). Ahmed et al. [39] isolated two new diterpenes, namely, verbenacine and salvinine, from S. verbenaca aerial parts (Table 1, Figure 6).

2.5. Bioeffective Properties

Different parts of S. verbenaca exhibit the presence of several bioactive molecules of antibacterial, antileishmanial, antioxidant, and anticancer activities (Figure 7).

2.5.1. Antibacterial Activity

The EOs and other organic extracts of S. verbenaca showed effective antibacterial effects against various gram-negative and gram-positive bacteria [7, 8, 10]. The inhibition zone diameter of S. verbenaca extracts and EOs and/or the minimum inhibitory concentration (MIC) are presented in (Table 3).

In Turkey, Sarac and Ugur [10] investigated the antibacterial potential of the ethanol extract from S. verbenaca aerial parts; they found that the extract showed a weak antibacterial activity, with IZD between 9 and 11 mm against the gram-positive bacteria Staphylococcus epidermidis (MU 30) (), Bacillus subtilis (ATCC 6633) (), S. aureus (MU 44) (), S. aureus (MU 38) (), and S. aureus (ATCC 25923) (), and no activity was seen against Streptococcus mutans (CNCTC8/77) and Micrococcus luteus (NRRL B-4375) and nor gram-negative bacteria, P. fluorescens (MU87), Escherichia coli (ATCC25922), Pseudomonas stutzeri (MU70), Pseudomonas aeruginosa (ATCC27853), Stenotrophomonas maltophilia (MU64), Chryseomonas luteola (MU65), and S. maltophilia (MU99). Moreover, the ethanolic extract prepared from 12 S. verbenaca exhibited lower antimicrobial activity than the methanolic extracts, as found by Kostić et al. [9].

The investigation of the methanol extract from aerial parts of Tunisian S. verbenaca demonstrated that the extract had a high antibacterial potential () against six bacteria isolated from the mouths of patients [42]. However, a South African extract of S. verbenaca that was made with methanol and chloroform had strong antibacterial properties against Klebsiella pneumoniae, Bacillus cereus, Escherichia coli, and Staphylococcus aureus [11]. Moreover, Belkhiri et al. [21] compared the antibacterial potential of four fractions from the methanol extract of Algerian S. verbenaca: chloroform extract, crude extract, aqueous extract, and ethyl acetate extract. They have found that the antibacterial efficacy increases with the concentration of the extract. Al-Zereini [7] also found that the ethyl acetate extract prepared from the leaves of S. verbenaca from Jordan had dose-dependent antibacterial properties against Bacillus brevis (ATCC 9999) and Bacillus subtilis (ATCC 6633). On the other hand, the extract had no effect on Klebsiella pneumoniae (ATCC 13883), Staphylococcus aureus (ATCC 43300), and Escherichia coli (ATCC 25922). Canzoneri et al. [8] found that the EO of S. verbenaca aerial parts has potential antibacterial effects, and this activity is much higher against gram-positive bacteria than gram-negatives.

2.5.2. Antioxidant Activity

The antioxidant potential of S. verbenaca extracts was investigated by several researchers [12, 21, 23, 38, 42–44], and Table 4 summarizes the majority of the investigations that were carried out on different parts of S. verbenaca, collected from different regions.

Kostić et al. [41] evaluated the antioxidant potential of different S. verbenaca extracts using the beta-carotene/linoleic acid system and DPPH assay. They found that the methanol extract had the highest activity in the DPPH method, while the ethanolic extract obtained by ultrasound extraction was the most active metabolite of beta-carotene/linoleic acid. The antioxidant activity of hydromethanolic extract prepared from stems and leaves of Moroccan species was carried out by Khlifi et al. [44]. The results showed that the extract had a significant antioxidant effect at 100 μg/mL, with a strong inhibition of oxygen consumption compared to previous studies [38].

The antioxidant potential of Tunisian S. verbenaca extracts was also studied [42], and the results showed that methanolic extract from aerial parts had lower activity () compared to the positive control, which was the trolox () using the DPPH assay. In addition, it was reported that the antioxidant activity over 20 minutes using the ABTS assay increased with time, but was still four times lower than the activity of trolox. Additionally, Farhat et al. [6] studied the efficacy of the collection sites on the antioxidant capacity of methanolic extract prepared from postdistilled aerial parts of Tunisian species. They found that the site had a significant effect on the antioxidant potential by the DPPH, ABTS, and FRAP methods. Likewise, activity was shown to be substantially linked with total phenolic content.

The antioxidant activity of some extracts of S. verbenaca collected from Algeria was mostly studied using the DPPH assay. It was found that the crude extract prepared from aerial parts had good antioxidant activity that increased with increasing the extract concentration [14]. The scavenging activity was 95% at a concentration of 0.1 mg/mL. Also, the methanol extract of S. verbenaca aerial parts revealed a high reducing power in the FRAP test [43] using the DPPH assay. Additionally, it was cited that the methanol extract had a beneficial effect against free-radical damage and exhibited a 5-fold more inhibitory effect than the standard antioxidant trolox () [12]. They also observed that the radical scavenging activity had no significant correlation with the phenolic content and a low correlation with the flavonoid content. Belkhiri et al. [21] investigated the antioxidant potential of some fractions of the methanol extracts using the DPPH method, metal chelating activity, and reducing power assay, and all extracts showed potent antioxidant activity [13]. The cupric ion reducing capacity (CUPRAC) and Fe³⁺ reducing capacity (phenanthroline assay) of the extracts were investigated, and the findings exhibited that both extracts had high antioxidant capacity, with methanolic extract exhibiting the highest activity [14].

2.5.3. Anticancer Activity

The different organic essential oils and extracts of S. verbenaca have been studied for anticancer properties. Numerous laboratory investigations using cell culture have shown that S. verbenaca extracts and essential oils have antiproliferative properties (Table 5) against a variety of cancer cell lines [15–19, 23, 45].

The ethyl acetate extract of S. verbenaca leaves produced after maceration was examined using the MDA cell lines MB-231 (human breast adenocarcinoma, ATCC HTB-26). The findings indicated that all extracts produced cytotoxicity in MDA MB-231 breast cancer cells [7]. However, it was proved that S. verbenaca leaf extracts possessed cytotoxic effect against HEp-2 (human larynx cancer cells) and Vero (monkey kidney cells) [18]. In another investigation, methanolic extracts of S. verbenaca’s aerial component prepared by maceration were evaluated in vitro against four human cancer cell lines, including HCA, HepG2, MCF-7, and HPC. The findings indicate that LC₅₀ levels higher than 75 μg/mL were deemed inactive [15]. Additionally, MTT assays were used to determine the cytotoxic activity of several extracts (methanol, hexane, ethyl acetate, n-butanol, and chloroform extracts) obtained from the aerial portion of S. verbenaca [16]. Methanol and chloroform extracts of S. verbenaca aerial parts were evaluated against colon adenocarcinoma (HT-29), human cancer cell lines (breast adenocarcinoma (MCF-7), human kidney epithelial cell line and glioblastoma (SF-268)) [17]. S. verbenaca exhibited more favorable action against MCF-7, with an IC₅₀ value of 31.50 13.70 μg/mL, but was inactive versus SF-268 and/or HT-29 cell lines [17].

A cell viability study was performed to avoid any cytotoxic concentration of S. verbenaca root extract on THP-1 cells. The MTT assay revealed that the most cytotoxic concentration of the extract was 1000 μg/mL, which caused 70% of cell death and 30% of cell viability [23]. The essential oils of S. verbena were investigated for their ability to suppress the proliferation of human tumor cells using the human M14 melanoma cell line and shown significant efficacy [19]. The antiproliferative effect of S. verbenaca essential oil may be attributed to active sesquiterpenes in combination with other natural chemicals found in the essential oil components. Indeed, carvacrol and thymol exhibited outstanding anticancer properties through a variety of mechanisms [19].

2.5.4. Antiparasitic Activity

Et-Touys et al. [20] investigated the antileishmanial effects of organic extracts (methanol, n-hexane, and dichloromethane extract) from S. verbenaca, and it was reported that the in vitro antileishmanial effect which was evaluated on the culture of three Leishmania species such as Leishmania infantum, Leishmania tropica, and Leishmania major was good (Table 6).

Belkhiri et al. [21] additionally observed that S. verbenaca has antihemolytic properties. In vitro antihemolytic activity of S. verbenaca extract was determined by inducing oxidative erythrocyte hemolysis. The results indicated that ethyl acetate extract was the most effective in inhibiting hemolysis, followed by crude extract, chloroform extract, and aqueous extract. Additionally, ethyl acetate extract inhibited hemolysis more effectively than vitamin C.

2.5.5. Insecticidal Activity

In most cases, the application of synthetic pesticides is the primary approach for controlling insect pests, which produces excellent effects in a short period of time. Meanwhile, their irrational usage has resulted in global issues such as pollution, nontarget toxicity, biodiversity loss, and the development of pest resistance [46–48]. This need arose from a desire to provide alternatives to synthetic insecticides, which can have negative environmental consequences [49–52]. The insecticidal capabilities of S. verbenaca extracts and essential oils have been documented to have potential impact against several pests in previous studies [53]. Insecticidal action has been shown in several experiments using some Salvia species [54].

Essential oils from Salvia species revealed 100% repellency activity against adults of Aedes albopictus [55]. The oil of S. verbenaca drastically shortened the lifespan of cowpea weevil and prevented females from laying eggs [56]. Several crude extracts and essential oils from Salvia species were tested for pesticide activity against the test pest larvae [57–59]. Insectistatic and insecticidal properties of chloroform extracts from the aerial portions of four Salvia species were examined [60]. S. verbenaca extracts are very effective against Culex quinquefasciatus mosquitos [61]. Caryophyllene oxide was the major component in the essential oil of S. verbenaca with 7.28 [62]. The insecticidal activity and fumigant toxicity of caryophyllene oxide were tested against two insect pests, and it was shown to be effective [63].

2.6. Other Biological Effects

Different extracts from S. verbenaca have also exhibited other biological activities such as antihemolytic, immunomodulatory, and enzyme inhibitory effects (Table 7).

2.6.1. Xanthine Oxidase Inhibitory Effect

Xanthine oxidase, abbreviated as XO, is an oxidoreductase that catalyzes the conversion of hypoxanthine to xanthine and xanthine to uric acid. Xanthine oxidase is generally present in the liver and in an inactive form in the blood in humans. A blood test for XO may identify liver impairment because xanthine oxidase is released into the blood in situations of severe liver injury [21].

2.6.2. Burn Recovery Activities

Guaouguaou et al. [24] evaluated the impact of three S. verbenaca extracts on the healing of burns in rats using hexane, ethyl acetate, and n-butanol. The results indicated that various Salvia verbenaca plant extracts were more effective than silver sulfadiazine (SSD) and that it is the most widely used topical treatment for injury, with healed areas of 29.17% (base), 44.34% (hexane), 47.55% (ethyl acetate), 49.16% (n-butanol), and 41.09% SSD.

2.6.3. In Vitro Antidiabetic Activity

Several earlier studies have shown S. verbenaca’s antidiabetic activity in vitro [13]. Additional studies are shown in Section 2.8 and Figure 8.

2.6.4. Immunomodulatory Effects

Previous studies investigated the immunomodulatory effects of S. verbenaca aerial parts [14]. The carbon clearance rate test was used to determine the immunostimulant potential of this plant on phagocytic activity. The phagocytic index was much higher in rats who were given S. verbenaca at a dose of 200 mg/kg than in rats who were not given the herb.

2.7. Toxicological Investigations of S. verbenaca

The toxicological investigations of S. verbenaca have not been well studied. However, some studies carried out recently have confirmed the safety of these plant extracts (Table 8). Indeed, a report by Guaouguaou et al. [64] focused on the acute and subchronic effects of S. verbenaca toxicity in mice and rats through oral and topical administration. The findings of the acute toxicity of the fractions derived from S. verbenaca (n-butanol, hexane, and ethyl acetate) demonstrated that the LD₅₀ of this plant after oral administration at 2000 mg kg^-1 is not deadly [64]. In order to complete the toxicity profile of this plant, more research should be done to find out how toxic it is over a long period of time.

2.8. Pharmacological Properties of S. verbenaca Main Volatile Compounds

Several studies examined the major volatile chemicals found in S. verbenaca, including carvacrol, thymol, and linalool. Studies showed that carvacrol has hypoglycemic properties through intrinsic mechanisms such as blood glucose and insulin level lowering [65]. Additionally, carvacrol resulted in a drop in glucose levels. Additionally, these substances were shown to enhance the activity of glucokinase and glucose-6-phosphate dehydrogenase in the liver [66]. Carvacrol inhibits the enzymes α-amylase and alpha-glucosidase in vitro [67] and beta-galactosidase in vitro [68]. Thymol was also able to normalize blood sugar, plasma insulin, HbA_1c, and the insulin resistance index in patients with hyperglycemia [69]. The levels of expression of genes involved in the production of insulin have been studied and reported in STZ-induced diabetic mice [70, 71], and a rise in Mafa and Pdx1 gene expression has been reported. Limonene is another major constituent of S. verbenaca that has been shown to improve glucose homeostasis. Indeed, this substance boosts hepatic glycogen and plasma glucose levels [72] (Figure 8).

The antidiabetic effect has been also revealed by linalool (another main compound of S. verbenaca) [73, 74]. Indeed, linalool lowered blood glucose, hemoglobin A1c, fructosamine, interleukin-6, and tumor necrosis factor-α (TNF-α), while it increased insulin levels [74].

The major phytochemical compounds of S. verbenaca exhibited remarkable antibacterial effects [75–77]. Rhayour et al. [70] investigated the impact of thymol on gram-positive and gram-negative microorganisms, including Bacillus subtilis and Escherichia coli [75–78]. Antibacterial activity is demonstrated by modifying cell shape, damaging cell walls and membranes, and limiting the development of some types of bacteria, including P. aeruginosa [79]. In addition, limonene was found to be antibacterial because it targeted microorganisms’ cytoplasmic membranes, weakened membrane integrity, blocked respiratory enzymes, and lost the proton motive force (Figure 9).

The anticancer properties of the major components in S. verbenaca (carvacrol, limonene, and thymol) have also been reported recently [80–82]. Thymol has been shown to have anticancer properties via a variety of mechanisms, including inducing severe DNA damage, including the production of reactive oxygen species (ROS) and subsequent increase in oxidative stress and/or mitochondrial dysfunction, or via the nuclear factor of activated T cell (NFAT-2) route [81]. Additionally, carvacrol increased apoptosis in cells, perhaps via activating mitochondrial apoptotic and signaling pathways [83].

3. Conclusions and Perspectives

S. verbenaca, a medicinal plant used in traditional medicine to cure a variety of ailments, was found to be abundant in bioactive chemicals such as flavonoids, terpenoids, and phenolic acids. Numerous pharmacological studies have demonstrated that S. verbenaca extracts and essential oils have extraordinarily beneficial effects on a variety of diseases, including those caused by microbes and those caused by dysregulation of homeostasis. Indeed, this plant demonstrated antibacterial, antidiabetic, anticancer, and immunomodulatory properties via a variety of mechanisms. However, further research should be conducted to find other pharmacodynamic targets. Additionally, pharmacokinetic studies should be conducted to ascertain the absorption, metabolism, and elimination of S. verbenaca bioactive components. Additionally, toxicological studies should be conducted to validate the safety of S. verbenaca extracts at various doses and delivery methods.

Data Availability

All the data are cited in the main text of this document.

Conflicts of Interest

No potential competing interest was reported by the authors.

Acknowledgments

The authors would like to thank the Deanship of Scientific Research at Umm Al-Qura University for supporting this work by Grant Code 22UQU4331100DSR01.

References

E. M. Abdallah, “Plants: an alternative source for antimicrobials,” Journal of Applied Pharmaceutical Science, vol. 1, no. 6, pp. 16–20, 2011.
View at: Google Scholar
H. I. Al-Jaber, S. M. Obeidat, F. U. Afifi, and H. Musa, “Aroma profile of two populations of Salvia verbenaca collected from two bio- geographical zones from Jordan,” Chemistry & Biodiversity, vol. 17, no. 2, article e1900553, 2020.
View at: Publisher Site | Google Scholar
G. Bonnier and R. Douin, “La grande flore en couleur de Gaston Bonnier, France, Suisse, Belgique et pays voisins,” Réédition de la flore complète illustrée en couleur de France, Suisse, Belgique, de G. Bonnier et R. Douin, Belin édit, vol. 4, 1990.
View at: Google Scholar
M. Esra, O. Cetin, A. Kahraman, F. Celep, and M. Dogan, “A cytomorphological study in some taxa of the genusSalviaL. (Lamiaceae),” Caryologia, vol. 64, no. 3, pp. 272–287, 2011.
View at: Publisher Site | Google Scholar
M. Z. Afzal-Rafii, “Contribution à l'étude cytotaxonomique du groupeSalvia verbenacaL,” Bulletin de la Société Botanique de France. Lettres Botaniques, vol. 126, no. 1, pp. 79–86, 1979.
View at: Publisher Site | Google Scholar
M. B. Farhat, J. A. Sotomayor, and M. J. Jordán, “_Salvia verbenaca_ L. essential oil: variation of yield and composition according to collection site and phenophase,” Biochemical Systematics and Ecology, vol. 82, pp. 35–43, 2019.
View at: Publisher Site | Google Scholar
A. Russo, V. Cardile, A. C. E. Graziano et al., “Comparison of essential oil components and in vitro anticancer activity in wild and cultivated Salvia verbenaca,” Natural Product Research, vol. 29, no. 17, pp. 1630–1640, 2015.
View at: Publisher Site | Google Scholar
M. Canzoneri, M. Bruno, S. Rosselli et al., “Chemical composition and biological activity ofSalvia VerbenacaEssential oil,” Natural Product Communications, vol. 6, no. 7, article 1934578X1100600725, 2011.
View at: Publisher Site | Google Scholar
A. Khouchlaa, A. Et-Touys, F. Lakhdar, F. E. Laasri, A. E. Y. El Idrissi, and F. Zaakour, “Ethnomedicinal use, phytochemistry, pharmacology, and toxicology of Salvia verbenaca L. : a review,” Biointerface Research in Applied Chemistry, vol. 12, no. 2, pp. 1437–1469, 2021.
View at: Publisher Site | Google Scholar
N. Sarac and A. Uğur, Antimicrobial activities and usage in folkloric medicine of some Lamiaceae species growing in Mugla, Turkey, Muğla Sıtkı Koçman Üniversitesi, 2007, http://acikerisim.mu.edu.tr/xmlui/handle/20.500.12809/7732.
G. P. P. Kamatou, R. L. Van Zyl, H. Davids, F. R. Van Heerden, A. C. U. Lourens, and A. M. Viljoen, “Antimalarial and anticancer activities of selected South African _Salvia_ species and isolated compounds from S. radula,” South African Journal of Botany, vol. 74, no. 2, pp. 238–243, 2008.
View at: Publisher Site | Google Scholar
A. Djeridane, M. Yousfi, B. Nadjemi, S. Maamri, F. Djireb, and P. Stocker, “Phenolic extracts from various Algerian plants as strong inhibitors of porcine liver carboxylesterase,” Journal of Enzyme Inhibition and Medicinal Chemistry, vol. 21, no. 6, pp. 719–726, 2006.
View at: Publisher Site | Google Scholar
W. Mamache, S. Amira, C. Ben Souici, H. Laouer, and F. Benchikh, “In vitro antioxidant, anticholinesterases, anti-α-amylase, and anti-α- glucosidase effects of Algerian Salvia aegyptiaca and Salvia verbenaca,” Journal of Food Biochemistry, vol. 44, no. 11, article e13472, 2020.
View at: Publisher Site | Google Scholar
M. Nassar, F. Zadri, and S. Slimani, “Assessment of the protective effect of the methnolic extract from Salvia verbenaca roots against oxidative damage induced by hydrogen peroxide (H₂O₂),” Turkish Journal Of Pharmaceutical Sciences, vol. 18, no. 3, pp. 360–366, 2020.
View at: Publisher Site | Google Scholar
R. B. Badisa, O. Tzakou, M. Couladis, and E. Pilarinou, “Cytotoxic activities ofSalvia. of the Labiatae family,” Pharmaceutical Biology, vol. 42, no. 8, pp. 640–645, 2005.
View at: Publisher Site | Google Scholar
F.-E. Guaouguaou, M. A. A. Bebaha, K. Taghzouti et al., “Cytotoxicological investigation of the essential oil and the extracts of Cotula cinerea and Salvia verbenaca from Morocco,” BioMed Research International, vol. 2018, Article ID 7163961, 5 pages, 2018.
View at: Publisher Site | Google Scholar
G. P. P. Kamatou, S. F. Van Vuuren, F. R. Van Heerden, T. Seaman, and A. M. Viljoen, “Antibacterial and antimycobacterial activities of South African _Salvia_ species and isolated compounds from _S. chamelaeagnea_,” South African Journal of Botany, vol. 73, no. 4, pp. 552–557, 2007.
View at: Publisher Site | Google Scholar
A. Latif, H. M. Amer, M. E. Hamad, S. A. R. Alarifi, and F. N. Almajhdi, “Medicinal plants from Saudi Arabia and Indonesia: in vitro cytotoxicity evaluation on Vero and Hep-2 cells,” Journal of Medicinal Plants Research, vol. 8, no. 34, pp. 1065–1073, 2014.
View at: Publisher Site | Google Scholar
A. Russo, V. Cardile, A. C. E. Graziano et al., “Comparison of essential oil components and in vitro anticancer activity in wild and cultivated Salvia verbenaca,” Natural Product Research, vol. 29, no. 17, pp. 1630–1640, 2015.
View at: Publisher Site | Google Scholar
A. Et-Touys, H. Fellah, F. Sebti et al., “In vitro antileishmanial activity of extracts from endemic Moroccan medicinal plant Salvia verbenaca (L.) Briq. ssp verbenaca Maire (S. clandestina Batt. non L),” European Journal of Medicinal Plants, vol. 16, no. 1, pp. 1–8, 2016.
View at: Publisher Site | Google Scholar
F. Belkhiri, A. Baghiani, M. M. Zerroug, and L. Arrar, “Investigation of antihemolytic, xanthine oxidase inhibition, antioxidant and antimicrobial properties of Salvia verbenaca L. aerial part extracts,” African Journal of Traditional, Complementary and Alternative Medicines, vol. 14, no. 2, pp. 273–281, 2017.
View at: Publisher Site | Google Scholar
L. Viegi, K. Ghedira, and K. Ghedira, “Preliminary study of plants used in ethnoveterinary medicine in Tunisia and in Italy,” African Journal of Traditional, Complementary and Alternative Medicines, vol. 11, no. 3, pp. 189–199, 2014.
View at: Publisher Site | Google Scholar
M. Nassar, S. Zerizer, Z. Kabouche, A. Kabouche, and S. Bechkri, “Antioxidant and the immunomodulatory activities exhibited by three plants from Lamiaceae family,” International Journal of Pharmacy & Pharmaceutical Sciences, vol. 7, no. 9, pp. 331–334, 2015.
View at: Google Scholar
F.-E. Guaouguaou, K. Taghzouti, M. Oukabli, and N. E. Es-Safi, “The effect of Salvia verbenaca extracts for healing of second-degree burn wounds in rats,” Current Bioactive Compounds, vol. 14, no. 4, pp. 419–427, 2018.
View at: Publisher Site | Google Scholar
M. Canzoneri, M. Bruno, S. Rosselli et al., “Chemical composition and biological activity of Salvia verbenaca essential oil,” Natural Product Communications, vol. 6, no. 7, article 1934578X1100600, 2011.
View at: Publisher Site | Google Scholar
E. Abbouyi, P. Ahmed, N. Filali-Ansari, P. S. Khyari, and H. Loukili, “Inventory of medicinal plants prescribed by traditional healers in El Jadida city and suburbs (Morocco),” International Journal of Green Pharmacy, vol. 8, no. 4, p. 242, 2014.
View at: Publisher Site | Google Scholar
I. Slimani, M. Najem, R. Belaidi et al., “Ethnobotanical survey of medicinal plants used in Zerhoun region, Morocco,” International Journal of Innovation and Applied Studies, vol. 15, no. 4, pp. 846–863, 2016.
View at: Google Scholar
A. Daoudi, M. Bammou, S. Zarkani, I. Slimani, J. Ibijbijen, and L. Nassiri, “Étude ethnobotanique de la flore médicinale dans la commune rurale d’Aguelmouss province de Khénifra (Maroc),” Phytothérapie, vol. 14, no. 4, pp. 220–228, 2016.
View at: Publisher Site | Google Scholar
N. Salhi, A. Bouyahya, S. Fettach, A. Zellou, and Y. Cherrah, “Ethnopharmacological study of medicinal plants used in the treatment of skin burns in occidental Morocco (area of Rabat),” South African Journal of Botany, vol. 121, pp. 128–142, 2019.
View at: Publisher Site | Google Scholar
A. Douira and L. Zidane, “Étude ethnobotanique des plantes médicinales utilisées dans le traitement du diabète, et des maladies cardiaques dans la région d’Izarène (Nord du Maroc),” Journal of Applied Biosciences, vol. 86, no. 1, pp. 7940–7956, 2015.
View at: Publisher Site | Google Scholar
M. Aissaoui, P. Chalard, G. Figuérédo et al., “Chemical composition of the essential oil of Salvia verbenaca (L.) Briq. ssp. pseudo-jaminiana (Chev.) M,” Research Journal of Pharmaceutical, Biological and Chemical Sciences, vol. 5, no. 6, pp. 368–372, 2014.
View at: Google Scholar
H. I. Al-Jaber, “Essential oil composition of the aerial parts of fresh and air-driedSalvia verbenacaL. growing wild in Jordan,” Journal of Essential Oil Bearing Plants, vol. 18, no. 3, pp. 718–724, 2015.
View at: Publisher Site | Google Scholar
M. B. Taârit, K. Msaada, K. Hosni, and B. Marzouk, “GC analyses of Salvia seeds as valuable essential oil source,” Advances in Chemistry, vol. 2014, Article ID 838162, 6 pages, 2014.
View at: Publisher Site | Google Scholar
D. Pitarokili, O. Tzakou, and A. Loukis, “Essential oil composition of Salvia verticillata, S. verbenaca, S. glutinosa and S. candidissima growing wild in Greece,” Flavour and Fragrance Journal, vol. 21, no. 4, pp. 670–673, 2006.
View at: Publisher Site | Google Scholar
A. Khemkham, S. Belhadj, R. Meddour et al., “HS-SPME-GC/MS analysis of 3 Lamiaceae plants: Ajuga iva (L.) Schreb., Salvia verbenaca L. and Thymus algeriensis Boiss. & Reut,” Journal of Fundamental and Applied Sciences, vol. 12, no. 2, pp. 700–711, 2020.
View at: Google Scholar
Z. Belloum, P. Chalard, G. Figuérédo et al., “Chemical composition of the essential oil of Salvia verbenaca (L.) Briq. ssp. clandestina (L.) Pugsl,” Research Journal of Pharmaceutical, Biological and Chemical Sciences, vol. 5, no. 6, pp. 262–265, 2014.
View at: Google Scholar
I. Özdek and H. Fakir, “Determination to leaf and flower volatile components of natural sage taxa (salvia spp.) of murat mountain (Kütahya-Gediz),” Turkish Journal of Forestry, vol. 20, no. 4, pp. 433–439, 2019.
View at: Publisher Site | Google Scholar
B. Tepe, O. Eminagaoglu, H. A. Akpulat, and E. Aydin, “Antioxidant potentials and rosmarinic acid levels of the methanolic extracts of Salvia verticillata (L.) subsp. verticillata and S. verticillata (L.) subsp. amasiaca (Freyn & Bornm.) Bornm,” Food Chemistry, vol. 100, no. 3, pp. 985–989, 2007.
View at: Publisher Site | Google Scholar
B. Ahmed, T. A. Al-Howiriny, A. J. Al-Rehaily, and J. S. Mossa, “Verbenacine and salvinine: two new diterpenes from Salvia verbenaca,” Zeitschrift für Naturforschung C, vol. 59, no. 1-2, pp. 9–14, 2004.
View at: Publisher Site | Google Scholar
A. Kabouche, Z. Kabouche, R. Touzani, and C. Bruneau, “Diterpenes and sterols from the roots of Salvia verbenaca subsp. clandestina,” Chemistry of Natural Compounds, vol. 44, no. 6, pp. 824-825, 2008.
View at: Publisher Site | Google Scholar
M. Kostić, B. Zlatković, B. Miladinović et al., “Rosmarinic acid levels, phenolic contents, antioxidant and antimicrobial activities of the extracts from Salvia verbenaca L. obtained with different solvents and procedures,” Journal of Food Biochemistry, vol. 39, no. 2, pp. 199–208, 2015.
View at: Publisher Site | Google Scholar
K. B. H. Salah, M. A. Mahjoub, S. Ammar et al., “Antimicrobial and antioxidant activities of the methanolic extracts of three Salvia species from Tunisia,” Natural Product Research, vol. 20, no. 12, pp. 1110–1120, 2006.
View at: Publisher Site | Google Scholar
N. Belmekki and N. Bendimerad, “Antioxidant activity and phenolic content in methanol crude extracts from three Lamiaceae grown in southwestern Algeria,” Journal of Natural Product and Plant Resources, vol. 2, no. 1, pp. 175–181, 2012.
View at: Google Scholar
S. Khlifi, Y. El Hachimi, A. Khalil et al., “In vitroantioxidant properties of Salvia verbenaca L. hydromethanolic extract,” Indian Journal of Pharmacology, vol. 38, no. 4, p. 276, 2006.
View at: Publisher Site | Google Scholar
W. A. Al-Zereini, “Ononis natrixandSalvia verbenaca: two Jordanian medicinal plants with cytotoxic and antibacterial activities,” Journal of Herbs, Spices & Medicinal Plants, vol. 23, no. 1, pp. 18–25, 2017.
View at: Publisher Site | Google Scholar
S. J. Yu, S. N. Nguyen, and G. E. Abo-Elghar, “Biochemical characteristics of insecticide resistance in the fall armyworm, Spodoptera frugiperda (J.E. Smith),” Pesticide Biochemistry and Physiology, vol. 77, no. 1, pp. 1–11, 2003.
View at: Publisher Site | Google Scholar
G. J. Devine and M. J. Furlong, “Insecticide use: contexts and ecological consequences,” Agriculture and Human Values, vol. 24, no. 3, pp. 281–306, 2007.
View at: Publisher Site | Google Scholar
C. A. Farnsworth, M. G. Teese, G. Yuan et al., “Esterase-based metabolic resistance to insecticides in heliothine and spodopteran pests,” Journal of Pesticide Science, vol. 35, no. 3, pp. 275–289, 2010.
View at: Publisher Site | Google Scholar
R. Pavela and T. Chermenskaya, “Potential insecticidal activity of extracts from 18 species of medicinal plants on larvae of Spodoptera littoralis–Short Communication,” Plant Protection Science, vol. 40, no. 4, pp. 145–150, 2010.
View at: Publisher Site | Google Scholar
R. Pavela, “Possibilities of botanical insecticide exploitation in plant protection,” Pest Technology, vol. 1, no. 1, pp. 47–52, 2007.
View at: Google Scholar
J. Pretty and Z. P. Bharucha, “Integrated pest management for sustainable intensification of agriculture in Asia and Africa,” Insects, vol. 6, no. 1, pp. 152–182, 2015.
View at: Publisher Site | Google Scholar
S. M. Hamed, A. A. Abd, N. A.-R. El-Rhman, and I. B. M. Ibraheem, “Role of marine macroalgae in plant protection & improvement for sustainable agriculture technology,” Beni-Suef University Journal of Basic and Applied Sciences, vol. 7, no. 1, pp. 104–110, 2018.
View at: Publisher Site | Google Scholar
N. C. Cárdenas-Ortega, M. M. González-Chávez, R. Figueroa-Brito et al., “Composition of the essential oil of Salvia ballotiflora (Lamiaceae) and its insecticidal activity,” Molecules, vol. 20, no. 5, pp. 8048–8059, 2015.
View at: Publisher Site | Google Scholar
Z. R. Karahroodi, S. Moharramipour, and A. Rahbarpour, “Investigated repellency effect of some essential oils of 17 native medicinal plants on adults Plodia interpunctella,” American-Eurasian Journal of Sustainable Agriculture, vol. 3, pp. 181–185, 2009.
View at: Google Scholar
B. Conti, G. Benelli, M. Leonardi et al., “Repellent effect of Salvia dorisiana, S. longifolia, and S. sclarea (Lamiaceae) essential oils against the mosquito Aedes albopictus Skuse (Diptera: Culicidae),” Parasitology Research, vol. 111, no. 1, pp. 291–299, 2012.
View at: Publisher Site | Google Scholar
R. A. Fatiha, R. Kada, M. A. Khelil, and J. Pujade-Villar, “Biological control against the cowpea weevil (Callosobruchus chinensis L., Coleoptera: Bruchidae) using essential oils of some medicinal plants,” Journal of Plant Protection Research, vol. 54, no. 3, pp. 211–217, 2014.
View at: Publisher Site | Google Scholar
H. Cetin, I. Cinbilgel, A. Yanikoglu, and M. Gokceoglu, “Larvicidal activity of some Labiatae (Lamiaceae) plant extracts from Turkey,” Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives, vol. 20, no. 12, pp. 1088–1090, 2006.
View at: Publisher Site | Google Scholar
B. Hosseini, A. Estaji, and S. M. Mehdi, “Fumigant toxicity of essential oil from‘Salvia leriifolia’(benth) against two stored product insect pests,” Australian Journal of Crop Science, vol. 7, no. 6, pp. 855–860, 2013.
View at: Publisher Site | Google Scholar
Z. Ulukanli, S. Karabörklü, M. Cenet, O. Sagdic, I. Ozturk, and M. Balcilar, “Essential oil composition, insecticidal and antibacterial activities of Salvia tomentosa Miller,” Medicinal Chemistry Research, vol. 22, no. 2, pp. 832–840, 2013.
View at: Publisher Site | Google Scholar
M. A. Zavala-Sánchez, S. P. Gutiérrez, D. Romo-Asunción, N. C. Cárdenas-Ortega, and M. A. Ramos-López, “Activity of fourSalviaspecies againstSpodoptera frugiperda(J.E. Smith) (Lepidoptera: Noctuidae),” Southwestern Entomologist, vol. 38, no. 1, pp. 67–73, 2013.
View at: Publisher Site | Google Scholar
R. Pavela, “Larvicidal effects of some Euro-Asiatic plants against Culex quinquefasciatus Say larvae (Diptera: Culicidae),” Parasitology Research, vol. 105, no. 3, pp. 887–892, 2009.
View at: Publisher Site | Google Scholar
M. Taarit, K. Ben, K. Msaada, N. B. Hosni, B. M. Amor, and M. E. Kchouk, “Chemical composition of the essential oils obtained from the leaves, fruits and stems ofSalvia verbenacaL. from the northeast region of Tunisia,” Journal of Essential Oil Research, vol. 22, no. 5, pp. 449–453, 2010.
View at: Publisher Site | Google Scholar
P. Liu, X.-C. Liu, H.-W. Dong, Z.-L. Liu, D. Shu-Shan, and Z.-W. Deng, “Chemical composition and insecticidal activity of the essential oil of Illicium pachyphyllum fruits against two grain storage insects,” Molecules, vol. 17, no. 12, pp. 14870–14881, 2012.
View at: Publisher Site | Google Scholar
F.-E. Guaouguaou, K. Taghzouti, M. Oukabli et al., “Acute and subchronic oral and dermal toxicological studies ofSalvia verbenacaextracts in mice and rats,” Journal of Herbs, Spices & Medicinal Plants, vol. 25, no. 1, pp. 33–42, 2019.
View at: Publisher Site | Google Scholar
K. G. Woon, J. H. Kyung, K. I. M. Do Yeon, and C. S. Hyun, “Beneficial effects of carvacrol on insulin resistance in high fat diet-induced diabetic mice,” Fall General Meeting and Academic Conference., vol. 1, pp. 281–281, 2013.
View at: Google Scholar
M. Ezhumalai, T. Radhiga, and K. V. Pugalendi, “Antihyperglycemic effect of carvacrol in combination with rosiglitazone in high-fat diet-induced type 2 diabetic C57BL/6J mice,” Molecular and Cellular Biochemistry, vol. 385, no. 1, pp. 23–31, 2014.
View at: Publisher Site | Google Scholar
S. Govindaraju and P. Indra Arulselvi, “Characterization of Coleus aromaticusessential oil and its major constituent carvacrol forin vitroantidiabetic and antiproliferative activities,” Journal of Herbs, Spices & Medicinal Plants, vol. 24, no. 1, pp. 37–51, 2018.
View at: Publisher Site | Google Scholar
J. Wang, X. Hu, W. Ai et al., “Phytol increases adipocyte number and glucose tolerance through activation of PI3K/Akt signaling pathway in mice fed high-fat and high-fructose diet,” Biochemical and Biophysical Research Communications, vol. 489, no. 4, pp. 432–438, 2017.
View at: Publisher Site | Google Scholar
S. Saravanan and L. Pari, “Role of thymol on hyperglycemia and hyperlipidemia in high fat diet-induced type 2 diabetic C57BL/6J mice,” European Journal of Pharmacology, vol. 761, pp. 279–287, 2015.
View at: Publisher Site | Google Scholar
K. Rhayour, T. Bouchikhi, A. Tantaoui-Elaraki, K. Sendide, and A. Remmal, “The mechanism of bactericidal action of oregano and clove essential oils and of their phenolic major components onEscherichia coliandBacillus subtilis,” Journal of Essential Oil Research, vol. 15, no. 5, pp. 356–362, 2003.
View at: Publisher Site | Google Scholar
A. S. Brujeni, “Thymol effect on the expression of Mafa and Pdx1 genes in streptozotocin-induced diabetic rats,” Razi Journal of Medical Sciences, vol. 26, no. 10, 2019.
View at: Google Scholar
R. Murali and R. Saravanan, “Antidiabetic effect of d-limonene, a monoterpene in streptozotocin-induced diabetic rats,” Biomedicine & Preventive Nutrition, vol. 2, no. 4, pp. 269–275, 2012.
View at: Publisher Site | Google Scholar
T. A. More, B. R. Kulkarni, M. L. Nalawade, and A. U. Arvindekar, “Antidiabetic activity of linalool and limonene in streptozotocin-induced diabetic rat: a combinatorial therapy approach,” International Journal of Pharmacy & Pharmaceutical Sciences, vol. 6, no. 8, pp. 159–163, 2014.
View at: Google Scholar
B. Deepa and C. V. Anuradha, “Linalool, a plant derived monoterpene alcohol, rescues kidney from diabetes-induced nephropathic changes via blood glucose reduction,” Diabetologia Croatica, vol. 40, no. 4, 2011.
View at: Google Scholar
W. Churklam, S. Chaturongakul, B. Ngamwongsatit, and R. Aunpad, “The mechanisms of action of carvacrol and its synergism with nisin against _Listeria monocytogenes_ on sliced bologna sausage,” Food Control, vol. 108, article 106864, 2020.
View at: Publisher Site | Google Scholar
A. Duarte, Â. Luís, M. Oleastro, and F. C. Domingues, “Antioxidant properties of coriander essential oil and linalool and their potential to control Campylobacter spp,” Food Control, vol. 61, pp. 115–122, 2016.
View at: Publisher Site | Google Scholar
K. Hąc-Wydro, M. Flasiński, and K. Romańczuk, “Essential oils as food eco-preservatives: model system studies on the effect of temperature on limonene antibacterial activity,” Food Chemistry, vol. 235, pp. 127–135, 2017.
View at: Publisher Site | Google Scholar
M. K. Swamy, M. S. Akhtar, and U. R. Sinniah, “Antimicrobial properties of plant essential oils against human pathogens and their mode of action: an updated review,” Evidence-based Complementary and Alternative Medicine, vol. 2016, 21 pages, 2016.
View at: Publisher Site | Google Scholar
X. Liu, J. Cai, H. Chen et al., “Antibacterial activity and mechanism of linalool against Pseudomonas aeruginosa,” Microbial Pathogenesis, vol. 141, article 103980, 2020.
View at: Publisher Site | Google Scholar
J. Baranauskaite, A. Kubiliene, M. Marksa et al., “The influence of different oregano species on the antioxidant activity determined using HPLC postcolumn DPPH method and anticancer activity of carvacrol and rosmarinic acid,” BioMed Research International, vol. 2017, 7 pages, 2017.
View at: Publisher Site | Google Scholar
M. T. Islam, A. B. R. Khalipha, R. Bagchi et al., “Anticancer activity of thymol: a literature-based review and docking study with emphasis on its anticancer mechanisms,” IUBMB Life, vol. 71, no. 1, pp. 9–19, 2019.
View at: Publisher Site | Google Scholar
K. Sekhar, A. R. Chandra, M. N. Bobby, and J. R. Kanala, “A review on anticancer potential of natural drugs: hispolon and limonene,” International Journal of Current Microbiology and Applied Sciences, vol. 7, no. 11, pp. 3253–3263, 2018.
View at: Publisher Site | Google Scholar
K. Fan, X. Li, Y. Cao et al., “Carvacrol inhibits proliferation and induces apoptosis in human colon cancer cells,” Anti-Cancer Drugs, vol. 26, no. 8, pp. 813–823, 2015.
View at: Publisher Site | Google Scholar

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