Next Article in Journal
A One-Pot Tandem Strategy in Catalytic Asymmetric Vinylogous Aldol Reaction of Homoallylic Alcohols
Next Article in Special Issue
Qingxuan Jiangya Decoction Reverses Vascular Remodeling by Inducing Vascular Smooth Muscle Cell Apoptosis in Spontaneously Hypertensive Rats
Previous Article in Journal
Recent Advances in Interface Engineering for Planar Heterojunction Perovskite Solar Cells
Previous Article in Special Issue
Natural Products to Counteract the Epidemic of Cardiovascular and Metabolic Disorders
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Molecules
Volume 21
Issue 7
10.3390/molecules21070826
molecules-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

Kazakh Ziziphora Species as Sources of Bioactive Substances

by
Karel Šmejkal
1,*,
Milan Malaník
1,
Karlygash Zhaparkulova
2,
Zuriyadda Sakipova
2,
Liliya Ibragimova
2,
Galya Ibadullaeva
2 and
Milan Žemlička
3
1
Department of Natural Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Brno 61242, Czech Republic
2
Department of Pharmaceutical Technology, Faculty of Pharmacy, Kazakh National Medical University, Almaty 050000, Kazakhstan
3
Department of Pharmacognosy and Botany, The University of Veterinary Medicine and Pharmacy in Košice, Košice 04181, Slovakia
*
Author to whom correspondence should be addressed.
Molecules 2016, 21(7), 826; https://doi.org/10.3390/molecules21070826
Submission received: 19 May 2016 / Revised: 16 June 2016 / Accepted: 18 June 2016 / Published: 25 June 2016
(This article belongs to the Special Issue Effects of Natural Products in the Context of Cardiometabolic Disease)
Versions Notes

Abstract

:
Ziziphora species represent the prototypical example of the Lamiaceae family. The phytochemicals present in Ziziphora include monoterpenic essential oils, triterpenes and phenolic substances belonging to the flavonoids. In Kazakh traditional medicine, Ziziphora species possess several medicinal uses. In particular, Z. bungeana Lam. and Z. clinopodioides Lam. are used for the treatment of illnesses related to the cardiovascular system or to combat different infections. Unfortunately, the majority of the information about the complex Ziziphora species is only available in Russian and Chinese language, therefore, we decided gather all available information on Kazakhstan Ziziphora, namely its content compounds, medicinal uses and published patents, to draw the attention of scientists to this very interesting plant with high medicinal potential.

1. Introduction

1.1. Taxonomy of Ziziphora spp. and Their Typical Habitat

Taxonomy of Ziziphora spp. is complicated, as its world population is represented by more than 30 different species. This genus belongs to a very large Lamiaceae family with very similar taxonomic signs. In the flora of Kazakhstan, this genus can be subdivided into six species: Z. bungeana Lam., Z. clinopodioides Lam., Z. interrupta Juz., Z. pamiroalaica Juz., Z. tenuior L., and Z. vichodceviana Tkatsch. ex Tuylaganova. It is not completely clear if Z. bungeana is not simply a subspecies derived from Z. clinopodioides [1].
Ziziphora plants are annual or perennial and herbaceous or sub-shrubby. Their leaves are short petiolate or sub-sessile; the leaf blade is abaxially glandular. Verticillasters are scattered on the leaf axils or crowded in a terminal capitulum; floral leaves occur as large as stem leaves or can be reduced. Ziziphora species blossom from June to September according to the surrounding conditions. The calyx of Ziziphora plants appears to be narrowly cylindric, straight to slightly curved, 13‑veined, villous, annulated at throat, obscurely 2‑lipped, with the upper lip 3‑toothed and lower lip 2‑toothed; the teeth are subequal, close together, rarely divergent after anthesis. The corolla limb of the flower is 2‑lipped: upper lip straight, margin entire, apex emarginate; lower lip spreading, 3‑lobed, and middle lobe narrower than suborbicular lateral lobes. The anterior stamens are fertile, reaching the upper corolla lip, and posterior stamens are rudimentary, short, or absent; anther cells are linear, with only 1 or 2 of them developed, and the others tend to be reduced to an appendage or absent. The style apex is unequally 2‑cleft, and the posterior lobe is short. The fruits are ovoid and smooth nutlets. As mentioned, around the world, there are about 25–30 species in Africa, Asia and Europe, and four different species in China. Kazakhstan flora is represented by six different species. The morphology of Z. bungeana and Z. clinopodioides is described in detail, and information about the phytochemically less explored species Z. tenuior, Z. pamiroalaica, Z. vichodceviana and Z. interupta can be found here [2,3].
Z. bungeana Lam. are aromatic subshrubs with woody roots. The stems are numerous, obliquely ascending to sub-erect, 12–30 cm long, woody at the base, branched, densely retrorse, pubescent, especially at apex. The petioles are pubescent; the leaves are narrowly lanceolate to ovate-lanceolate, rarely ovate, 5–15 mm × 1.5–6 mm, sub-glabrous or pubescent, conspicuously glandular, base cuneate to attenuate, margin entire, apex acute to slightly obtuse. The verticillasters are crowded in globose or semiglobose terminal capitula; the floral leaves are reduced, mostly ascending or horizontal. The pedicel is 1–3 mm long. The calyx is tubular, 5(–7) mm, obscurely glandular; the teeth are subequal and acute. The corolla rose, ca. 8 mm, tube pubescent, and lateral lobes are circular. Usually, 2 stamens are fertile, and the posterior stamens are short or absent. The flowering period is typically in Aug-Sep. Z. bungeana grows in gravelly hillsides, semi-desert areas, or sandy beaches, at altitudes of 700–1100 m above sea level in the areas of Xinjiang (China), Kazakhstan, Kyrgyzstan, Mongolia, Russia, Tajikistan, Turkmenistan, and Uzbekistan [2].
Z. clinopodioides Lam. has a thick and woody rhizome. The stems are numerous, simple, erect, 8–40 cm long, rarely branched, but branching on the top, somewhat ascending, covered with short hairs bent down. The leaves are petiolate, ovate or oblong-ovate, 10–25 mm long, 3–10 mm wide, with entire or unclearly rarely toothed margin. The leaves are point-ferruginous, smooth or sparsely short-haired. The flowers are gathered in dense apical capitate inflorescences surrounded by small bracts. The calyx is covered with short hairs, corolla is 10–12 mm long, pink or light purple outside, short and fluffy, tubular, twice as long as the limb, with the upper lip oblong to oval and notched, the middle part of the lower lip almost formy and villous, and lateral lobes spit ovate. Z. clinopodioides Lam. grows typically on the open rocky and gravelly slopes of hills and mountains, on rocky riverbanks, and also on the steppe meadows [2].

1.2. The Traditional Utilization of Ziziphora spp.

Z. clinopodioides is well known in Chinese traditional medicine as lip vanilla, leaflet mint or mountain mint. According to Chinese Materia Medica, it is used as a tranquilizing agent. It is also used to treat palpitations, insomnia, cold and fever, and oedema. It is usually administered orally as a decoction prepared by placing 15–18 g of the plant in boiling water to brew a tea. Z. clinopodioides is found to have been used in folk medicine to treat fevers and headaches in Xinjiang, China [4]. It is also a medicinal plant used in traditional Uighur medicine for many purposes, e.g., treatment of heart disease, high blood pressure, asthma, hyperhidrosis, palpitation, insomnia, edema, cough, bronchitis, lung abscess and other diseases [5,6]. Z. clinopodioides leaves, flowers and stems are frequently used as wild vegetables or additives in food to obtain a strong aroma and flavour [7].
Z. clinopodioides (known as blue mint bush in Turkish and Iranian traditional medicine) is well known for its antibacterial action [8]. Ziziphora species are used frequently also in Turkish and Iranian folk medicine, mainly as infusions for sedative, stomachic, carminative and other effects. Their antiseptic and wound healing effect is also well known [6,9]. In Anatolia, Z. clinopodioides is used as a wild vegetable or aroma and flavour adding spice. The plant is locally known as Kirnanesi and is prepared as an aromatic tea for treating gastrointestinal disorders and for its carminative, antiseptic and wound-healing properties [6]. Furthermore, it used as a culinary agent for manufacturing a special type of cheese [10,11].
Z. tenuior L. (known as raushangul in Kazakh language and kakuti in Persian language; kakuti-e kuhi is the Persian name of Z. clinopodioides according to Beikmohammadi [8]), is used in traditional medicine for treatment of fever, dysentery, uterus infection and as an analgesic. It is used also to combat different gastrointestinal disorders, especially as a carminative, or as a remedial agent for diarrhoea or nausea. The essential oils and main components pulegone (53), thymol (62), menthone/isomenthone (44) and piperitone (45) could be the compounds responsible for the above-mentioned medicinal properties [12]. Z. tenuior has high content of essential oil, meaning it is a good raw source of pulegone (53) which is widely used in the food and drug industry [13,14]. Sezik et al. found this plant (local name Chulhulva) to have hypotensive properties in their ethnopharmacological research on the medicinal plants of Uzbekistan [13].
Z. bungeana herb is used in Uygur medicine to prepare oral decoction which relieves respiratory distress, dizziness and other symptoms connected to cardiovascular diseases like coronary heart disease or hypertension [14].

2. Ziziphora Phytochemistry and Pharmacology

The previous investigations which were carried out on the Ziziphora genus with aim to elucidate the phytochemical profiles were mainly focused on its essential oil composition, and this will be discussed in the following text. In addition to essential oils, the Ziziphora species can be sources of flavonoids, caffeic acid derivatives, fatty acids, triterpenes and sterols. Ding et al. attempted to determine the effect of growth stage of Z. clinopodioides on the content and composition of essential oils, terpenoids, phenolics and flavonoids, showing that essential oil content was higher during the flowering period from non-volatile compounds and only the total flavonoid content was strongly affected by the growth stage [15]. Similar results were shown by Razmjoue and Zarei, where the essential oil content was correlated to temperature, relative moisture and height above sea level [16]. The habitat was also a factor affecting the content of the compounds present in the essential oils of Z. clinopodioides [17]. Moreover, different chemovars were identified during the chemical analysis of Z. clinopodioides and Iranian Z. clinopodioides ssp. rigida. The content of main essential oils components varied and allowed authors to classify analyzed species into pulegone/neomenthol, pulegone, pulegone/1,8-cineol, neomenthol and 1,8-cineol/terpinen-4-ol chemotypes [18,19].
Water and ethanol extracts of Z. clinopodioides showed no activity against several bacterial species, but some activity against COX-1 was recorded [20]. When different extracts from Z. clinopodioides subsp. rigida were tested for antibacterial activity against several Gram-positive and Gram-negative bacterial strains, only low activity was noted (with the exception of deodorized hot water and water-soluble methanol extracts against Bacillus subtillis and methanol and water-insoluble methanol extract against E. coli) [21]. However, methanol-water extracts of Z. clinopodioides and Z. tenuior showed low activity against several Gram-positive and Gram-negative microbial species in other assays [22].
The efficacy of methanolic extract obtained from Z. clinopodioides for treating inflammatory bowel disease was tested using the dextran sulphate-induced colitis model in mice. The parameters of inflammatory process were observed and it was found that TNF-α and NO levels were decreased, and the level of antioxidative defence was restored to almost the normal level [23]. Promising results in mice model of acetic acid-induced collitis showed also the water soluble portion of methanolic extract of Z. clinopodioides, however, compounds responsible for effect were probably not the components of essential oil [24]. The effect observed in this assay could be connected with antioxidant activity, as myeloperoxidase and TBARS levels were decreased by pretreatment of mice with different Z. clinopodioides extract concentrations. All doses of Z. clinopodioides showed significantly lowered score values of macroscopic and microscopic evaluations of colons, the effect of Z. clinopodioides at concentration of 300 mg/kg was comparable to that of prednisolone. The anti-inflammatory potential of Ziziphora was confirmed also by further study which showed, that ethanolic extract of Z. tenuior is active in induction of CD40 expression on dendritic cells and it can modulate the immunity response by affection of cytokine secretion, what at least partially explaines the traditional usage of this plant in treatment of imunity related diseases [25]. Z. tenuior hydroalcoholic extract showed the antinociceptive activity (against visceral pain) in acetic acid-induced writhing assay in mice [26].
The methanolic extract of Z. clinopodioides subsp. rigida showed higher DPPH scavenging effect than the essential oil and other types of extracts [21].
Ziziphora extracts were tested for their potential cytotoxic effect in gastric cancer AGS cell line and showed promising cytotoxic activity [27].
Z. tenuior methanol and ethanol extracts showed the ability to decrease the bitterness of caffeine and showed some antioxidant activity, making Z. tenuior a promising food additive [28]. Some experiments also showed the reducing power of the water extract of Z. tenuior in the process of the formulation of silver nanoparticles [29].
The following chapters present an overview of the compounds identified from Kazakhstan Ziziphora species and their biological effects. Table 1, Table 2, Table 3 and Table 4 outline the Ziziphora compounds and their activities. The information pertaining to each single compound which was isolated or identified in Kazakhstan Ziziphora species is presented here to attract attention to these interesting plants with several possible uses. The data in this research were collected using the Scifinder portal, Web of Knowledge and Science Direct. The search included articles published till April 2016, which are written in English (with limited number of papers in Russian language). The search was conducted using each single compound detected in Ziziphora as keyword. The articles that presented results of compounds added to mixtures as well as those that appeared in congress abstracts were not considered in this review.

2.1. Patents

There are several patents registered for the Ziziphora species and their application (or application of their isolated compounds) in the area of medicine. Capsules containing the mixture of dried aerial part extract Z. bungeana with Artemisia rupestris and Arctium lappa extracts are used to treat different viral infections of the upper respiratory tract. The patent applications also include the assays on the antipyretic activity of the extract in rabbits, anti-inflammatory activity in rats and antitussic activity in mice. The antiviral activity of the preparation was also evaluated in vitro [30].
The method for obtaining the flavonoid fraction of the Z. bungeana extract was also patented, combining the extraction of the Z. bungeana aerial part with organic solvent, with the dispersion of the extract into aqueous phase and filtration through macroporous resin, further washed with ethanol to get a flavonoid-rich extract [31]. This flavonoid fraction is believed to be useful in the treatment of cardiovascular diseases. Other patents cover the usage of Z. bungeana polyphenol and flavonoid fraction [32]. A flavonoid preparation from Z. bungeana to treat cardiovascular disorders is also patented [33].
Z. clinopodioides is also a component of Chinese traditional medicinal preparation for the treatment of paroxysmal supraventricular tachycardia [34]. Z. clinopodioides essential oil can be used as an oral spray to improve hygiene of oral cavity, suppress inflammation and suppress the growth of oral pathogenic bacteria [35]. Z. clinopodioides essential oil can be used in agriculture. The method for obtaining this oil and its application as an anti-fungal preparation against plant pathogenic fungus Sclerotinia sclerotiorum was patented [36]. The HPLC fingerprint for Z. clinopodioides compounds has also been developed using reversed-phase chromatography of diosmin (7), linarin (8) and pulegone (53) [37].

2.2. Phenolics

Z. clinopodioides was extracted with aim to obtain extracts with different polarity compounds to determine the total polyphenol and flavonoid content. As shown, phenolic substances are concentrated in the ethyl acetate extract, similar to flavonoids, phenolic acids and some other phenolics [5]. However, the analysis of the literature on the isolation of flavonoids or further phenolics from Ziziphora showed the presence of mainly lipophilic compounds of aglycone type (Table 1). From flavonoids, only a limited number of glycosides (diosmin (7) and linarin (8)) was isolated.
Several aglycons, which can be called as dietary aglycons (like apigenin (1) and luteolin (3)) were also obtained. Typically, from Lamiaceae plants, lipophilic methoxylated aglycons were extracted, e.g., thymonin (4) or acacetin (5). Some relatively uncommon fatty acid-substituted flavones ziziphorin A and B (9 and 10) were isolated from Z. tenuior [38]. Furthermore, several phenolic acids and their esters, like caffeic acid (17) and its ethyl ester (18) and rosmarinic acid (19), salicylic acid (20) and benzoic acid (21), and derivatives of benzyl alcohol were detected in Ziziphora species (Table 1). The bioactivity of Ziziphora flavonoids was studied for several single compounds; therefore, we will mention the activities in connection to possible Ziziphora use. Generally, flavonoids from Ziziphora species showed antioxidant, anti-inflammatory, venoprotective and anticancer activity. Several lipophilic flavonoids showed also antibacterial properties.
The antioxidant activity of flavonoid substances depends on the arrangement of the functionalities on the skeleton. Especially, the substitution and number of hydroxyl groups affects the antioxidant activity mediated by radical scavenging and metal ion chelation. As the substitution of Ziziphora-isolated flavonoids is not entirely favourable for scavenging and chelation, the antioxidant effect may be more related with suppression of ROS formation either by inhibition of enzymes or by upregulation or protection of antioxidant defences. Flavonoids contribute to ROS generation inhibition by the affection of the enzymes involved in their production, like microsomal monooxygenase, glutathione S-transferase, mitochondrial succinoxidase, NADH oxidase, and others. The antioxidant activity of Z. clinopodioides was tested by several methods (DPPH, superoxide, and hydroxyl radical scavenging activity). Given the high polyphenol and flavonoid content, the greatest activity was observed in ethyl acetate extract [5]. Monoterpenic glucoside shizonepetoside A (83) and simple flavonoids apigenin (1), luteolin (3) and diosmetin (6) showed potent inhibitory effects on NO production. The stereochemistry of monoterpenic glucosides is important for this effect according to these results [4]. Vasorelaxant activity was shown by those Z. clinopodioides extracts that had high concentration of polyphenolic substances [135]. The mechanism of its vasorelaxant action was also elucidated. The bioactivity guided separation of CH2Cl2 part of a hydroalcoholic extract of the whole plant, using an in vitro model of rat-isolated thoracic aortic rings led to isolation of several compounds, from which apigenin (1) and chrysin (2) showed the greatest activity [39]. Therefore, some structure-activity relationships can be assumed: the presence of 4′-hydroxy group of flavonoid, no methyl substitution at C-4′ and absence of continual substitution at positions 5, 6 and 7 of the flavonoid skeleton [39]. These results should be interpreted carefully, as these tests were carried out ex vivo on normal rat aortas, and differences can be observed after application of compounds or extracts to hypertonic animals or human.
In general, lipophilic flavonoids (flavonoids aglycons or methoxylated and prenylated flavonoids) are synthesized by plants as a part of defence against microbial infection; therefore, they can be used for antimicrobial therapy in humans. Lipophilic flavonoids isolated from Ziziphora species like chrysin (2), acacetin (5) or thymonin (4) have antimicrobial effects and are components of, for example, propolis, a well-known antimicrobial active material [50,61]. Antibacterial flavonoids probably possess multiple cellular targets rather than one specific site of action. One of their actions at the molecular level is to form a complex with proteins through nonspecific forces such as hydrogen bonding and hydrophobic effects as well as by covalent bond formation. Thus, their mode of antimicrobial action may be related to their ability to inactivate microbial adhesins, enzymes, cell envelope transport proteins, and others [136]. Lipophilic flavonoids can also kill microbes by causing disruption of the microbial membranes [136]. Therefore, the presence of a number of lipophilic flavonoids can contribute to overall antibacterial effect of the traditional medicinal usage of Ziziphora extracts.
As it is well known, inflammation is a normal biological process in response to tissue injury, microbial pathogen infection, and chemical irritation. Inflammation is initiated by migration of immune cells from the blood vessels and release of mediators at the site of damage. This process is followed by further recruitment of inflammatory cells and release of reactive oxygen and nitrogen species and pro-inflammatory cytokines to combat the cause of inflammation, and later to repair caused damage. Acute inflammatory process is rapid and self-limiting, but prolonged inflammation triggers chronic disorders. Natural products are often used to combat diseases connected with chronic inflammation [137,138]. The effectiveness of methanolic extract obtained from Z. clinopodioides for treating inflammatory bowel disease was tested in dextran sulphate-induced colitis model in mice. The parameters of inflammatory process were observed and it was found that the TNF-α level and NO level were decreased and level of antioxidative defence was restored to almost normal level [23]. Ziziphora is relatively rich in flavonoids, which can be considered responsible for the anti-inflammatory potential of this plant. Flavonoids like apigenin (1) [46], luteolin (3) [53,54], diosmin (7) [82], its aglycone diosmetin (6) [79] and linarin (8) [88,89] are reported to possess anti-inflammatory effects.
Caffeic acid (17) and its derivatives are often connected with different therapeutical applications: their potential anticancer activity was well reviewed [98], their effects on the cardiovascular system were reviewed by Fuentes and Palomo [99] and a large review on general applications of caffeic acid (17) was published recently [100]. Similar activities were observed for caffeic acid ethylester (18). This compound showed antihypertensive, antioxidant and anti-inflammatory activities that can be connected with usage of Ziziphora against diseases of cardiovascular system [101,102,103,104,105,106,107,108,109,110,111,112]. Similarly, rosmarinic acid (19) possesses various activities, also connected with civilization diseases like cardiovascular system illnesses, chronic inflammations and cancer [113,114,115,116].

2.3. Triterpenes and Steroids

There is not much information about triterpenes obtained from Ziziphora species, however, their presence is confirmed and some unpublished results showed their relatively high concentrations. The main triterpenic compounds identified till date in Ziziphora spp. are oleanolic acid (26), ursolic acid (27) and maslinic acid (28), together with daucosterol (29) as a representative of plant steroids. The bioactivity of all these compounds was well reviewed (with the exception of 29) [139,140].
Oleanolic acid (26) and maslinic acid (28) are representatives of β-amyrin type of pentacyclic triterpenes with the carboxyl group at position C-17 of the triterpenic skeleton. Both these compounds are relatively abundant in nature and are active components of many plants with medicinal properties. Oleanolic (26) and maslinic (28) acids and their derivatives are often used as components in medical drugs with effect on the cardiovascular system. These compounds help combat different so-called “civilization” diseases, for example cardiovascular diseases including atherosclerosis and diabetes, and even cancer. This could be because they have anti-inflammatory and antioxidative properties, and both cytoprotective and cytotoxic activity depending on the conditions and type of cells. Albeit, their activity is relatively indistinctive, and the multiple potentials of these triterpenes makes them good candidates for semi-synthesis and synthesis of potent drugs [141]. Ursolic acid (27) is an α-amyrin type of triterpene, again with carboxylic function at C-17. Similarly to oleanolic (26) and maslinic (28) acid, it can be isolated from several plant species with potent medicinal properties [142]. Similar to previously mentioned triterpenic acids, it shows activities beneficial in the treatment of civilization diseases like for example cancer, cardiovascular diseases or chronic inflammations [142].
Concerning the folk usage and effects of Ziziphora, oleanolic acid (26) and maslinic (28) acid have been found to affect the cardiovascular system. Both these compounds work against LDL oxidation, thus showing antiatherogenic properties. Oleanolic acid (27) also causes vascular smooth muscle relaxation. 28 acts as a strong antioxidant and possesses hypoglycemic properties; it was found to reduce the insulin resistance in the mouse model of genetic type 2 diabetes. 26 is also a potent antioxidant interfering with the glutathione redox cycle, affecting the Fenton reaction, NADPH oxidase, Nrf2 and others [142]. Its anti-inflammatory effects are connected mainly with interaction with NF-κB, STAT3 dimerization and overall inhibition of gene expression of pro-inflammatory factors (COX, iNOS) [142].
Ziziphora species extracts are also connected with antibacterial effect, and the activity of ursolic acid (27) was proven against numerous Gram-positive and Gram-negative bacteria, including vancomycin-resistant Enterococcus and different Mycobacterium tuberculosis strains. Some antiviral, anti-parasitic and antifungal activity was also observed [142]. However, the authors of the majority of the cited papers are right in that more studies should be carried out to prove these effects in vivo in humans [144].
Daucosterol (29) is a natural phytosterol—a glucoside derived form β-sitosterol. As we did not find relevant information about its bioactivity, we tried to summarise its effects in Table 2. Several activities of daucosterol (29) are again in accordance with therapeutic potential of Ziziphora species observed both in folk medicine and scientific studies. The anti-inflammatory effect of daucosterol (29) was observed both in vitro and in vivo [152,153] and a 5-LOX inhibitory effect was observed [154]. Daucosterol (29) also acts as scavenger of free radicals in vitro [155] and as an antioxidant [156] and it inhibits nitric oxide production in LPS-activated RAW264.7 cells [157]. Furthermore, 29 showed antiproliferative [164,166] and cytotoxic [167] activity against different cancer cell lines; it induces apoptosis [165] and inhibits MDA-MB-231 cancer cell migration [169]. Some antimicrobial activities of 29 were observed, mainly against E. coli, S. aureus and H. pylori. The inhibition of H. pylori growth can be beneficial in the treatment of gastric ulcer lesions, because daucosterol (29)-mediated suppression of HCl/ethanol-induced gastric lesions was observed by Jeong et al. [177].

2.4. Essential Oil

The essential oils are probably the most studied part of Ziziphora phytochemical components (Table 3). As could be expected for Lamiaceae, these essential oils are predominantly composed of monoterpenic compounds; however, several sesquiterpenic substances and some other compounds were also identified by GC-MS analysis (see Table 3). The hydrodistillation is the commonly used method for obtaining Ziziphora essential oils, but the method used for obtaining Z. tenuior essential oil by supercritical fluid extraction (SFE) with higher yield was also published [179]. It is clear that the relative ratios of components vary according to the frequently occurring chemotypes in the family Lamiaceae, environmental factors, geographic origin and also extraction method [180,181,182]. For example, although we can see biochemical convergence among the Z. clinopodioides from different locations, owing to the frequent occurrence of chemotypes, different patterns in the composition of the oils are common. As mentioned above, the variability of essential oils components in Ziziphora species is really high and chemovars of one species can be found in very related habitats, as showed for example by Khodaverdi-Samani et al., who identified several chemovars of Z. clinopodioides ssp. rigida in limited area of southwestern Iran (Alpine type mountains). The essential oils obtained by hydro-distillation (content ranged from 0.12 to 0.98 mL/100 g of dry weight) were analyzed by GC and GC/MS to prove that the main chemical compositions were pulegone (53) (5.19% to 57.85%), limonene (38) (0.26% to 12.79%), 1,8-cineole (72) (0.00% to 27.4%), bornyl acetate (69) (0.47% to 9.37%), piperitenone (46) (0.70% to 9.05%) and menthol derivatives (for example 58) [19]. Other study revealed Z. clinopodioides as plant rich in carvacrol (73) 52.7%, linalool (66) 15.9% and menthol (56) 14% [183]. Further literature survey indicated that the oils of Ziziphora species have been found to be rich in pulegone (53) and thymol (62), but there are also analysis showing low or no concentration of these substances in Z. clinopodioides essential oil [184]. The composition of Z. clinopodioides essential oil is strongly influenced by flowering stage [182]. Also, the composition of Z. tenuior and Z. pamiroalaica essential oil may vary strongly [185]. Z. bungeana and Z. clinopodioides were analysed by the same group [185], same as Z. vychodceviana [186].
Essential oils are almost always complex mixtures of numerous substances, and therefore their biological effects are often described as the result of a synergism of all molecules or they mirror major activities of molecules present at the highest concentrations [418]. Moreover, the synergistic action is beneficial because the bacteria can undergo adaptation to maintain their membrane functionality in the presence of sub-inhibitory concentrations of antibacterial compounds and the resistance can occur, but the complex action of essential oil can help suppress this resistance [419].
Therefore, only the biological activities of essential oils in their entirety or of their main compounds have usually been evaluated. There are some reports about bioactivities of Ziziphora essential oils, mainly connected with evaluation of antibacterial activity. Moreover, antioxidant properties and anti-inflammatory effect was evaluated using different methods. 5-LOX was inhibited by Z. clinopodioides esstential oil (could be due to the presence of compounds structurally related to fatty acids serving as substrate of LOX) [420].
Generally, the major compounds reflect the biophysical and biological characteristics of the parent essential oils quite well (as visible for example for Origanum oil and carvacrol (73) [421]), and the exhibition of their effects depends on their concentration [422,423]. The very complex mixture of compounds present in essential oil also strongly affects the smell, thickness, texture, colour and cell penetration [424], lipophilic or hydrophilic attraction and fixation on cell walls and membranes, and cellular distribution [418]. Therefore, it is sometimes better to analyse the activity of the entire essential oil and compare it with the activity of pure main components. However, some reports highlight the antagonism of single components of essential oil [281,425], so the information about the activity of pure compounds could be useful. As visible from Table 3, we tried to summarize all information about biological effects of compounds present in Ziziphora essential oils available in recent literature, but for some compounds the information is missing or it is scarce.
Reports on the essential oils of different Ziziphora species often discuss their antibacterial activity. The essential oils obtained from different Kazakh Ziziphora species are generally rich in oxygenated monoterpenes (see Table 3); their antibacterial effect can be attributed to the presence of these compounds; however, this effect is not the consequence of the presence of oxygenated monoterpenes only. Z. clinopodioides essential oils were found to be effective against both Gram-negative and Gram-positive bacterial species [184,426]. The presence of thymol (62) could be responsible for the antibacterial activity. The activity of Z. tenuior essential oil was lower [426]. Similar results have been presented by Salehi et al. [21], showing good activity of Z clinopodioides subsp. rigida essential oil against several bacterial strains (with the exception of insensitive P. aeruginosa). Thymol (62) and pulegone (53) showed at least partial responsibility for the antibacterial effects of these materials. Also, the assays carried out on Z. clinopodioides subsp. bungeana essential oils showed activity against both Gram-positive and negative bacterial species, and pulegone (53) and 1,8‑cineol (72) were assigned as compounds responsible for the effect [201]. The high concentration of pulegone (53) is mentioned when the antimicrobial activity of essential oils is analysed: it showed activity especially against C. albicans and S. typhimurium. C. albicans was found to be susceptible to pulegone (53), which was found to be twice as effective as nystatin [427,428].
In other test, the antibacterial activity of essential oil and methanolic extract from Z. clinopodioides was compared using 52 Gram-positive and Gram-negative bacterial species, with disc diffusion method [11]. Both tested materials varied in level of activity, with much higher activity of essential oil. Pulegone (53), limonene (38), and piperitone (45) appeared to be the most active substances; however, further information about antibacterial activity of these compounds is not abundant.
We attempted to summarise compounds found in the literature with the antibacterial effect of Ziziphora essential oils and, if possible, their underlying mechanisms (Table 3). Carvacrol (73) and thymol (62) are placed in the first place, as their antibacterial and antiseptic effect is well known [429]. Their synergic action has been described previously and is well reviewed [369]. Carvacrol (73) acts on B. cereus via depletion of intracellular ATP pool, changes the membrane potential and increase the permeability of membrane for protons and potassium. Carvacrol (73) integrates into the lipidic monolayer of the cell membrane, changes its fluidity and damaging its functions [430]. There are evidences of other mechanisms of antibacterial effect, such as interaction with DNA. Moreover, application of carvacrol (73) has been found to inhibit the formation of bacterial biofilm, which is one of the mechanisms of bacterial resistance [369].
Thymol (62), an aromatic p‑menthane type monoterpene phenol, isomeric to carvacrol (73), is established as a good antimicrobial agent, interacting both with outer and inner cytoplasmic cell membranes via incorporation of the polar head group region into the lipid bilayer. This interaction changes the properties of the cell membrane and leads to its increased permeability/disintegration [431,432,433]. Moreover, thymol (62) can also up- or down-regulate the genes encoding the outer membrane protein synthesis. Beside this, it is able to inhibit the enzymes involved in protection against thermal stress, to affect the synthesis of ATP or to alter citric acid metabolic pathways [434,435].
As mentioned above, carvacrol (73) and thymol (62) exert a synergic effect, similar to many other combinations of components of essential oils against different common human pathogens (carvacrol/thymol (73/62), terpinene‑4‑ol/myrcene (70/31), carvacrol/p‑cymene (73), eugenol/thymol (25/62), eugenol/carvacrol (25/73), cinnamaldehyde/eugenol (106/25), citronellol/geraniol and others) [436,437,438]. The synergic action of p‑cymene and carvacrol (73) combination is based on the high affinity of p‑cymene to the cytoplasmic membrane and its bonding to the membrane causes its expansion, altering its potential and resulting in its higher sensitivity to the action of carvacrol (73) [358]. Some of these combinations of compounds with synergic activities are also present in Ziziphora essential oils. The mechanism of thymol (62) and carvacrol (73) synergism was also elucidated and reviewed [132,439]; however, the mechanistic studies describing the mechanisms of synergy are relatively scarce. Owing to their hydrophobic nature, 73 and 62 interact with the lipid bilayer of cytoplasmic membranes, causing loss of integrity and leakage of cellular material. This effect can, in general, increase the permeability of the membrane to other antimicrobial compounds by general disintegration of the membrane or by formation of a large number of pores.
The synergic activity of some terpenoids can be also observed for other organisms than bacteria, e.g., Meloidogyne incognita [440]. Synergic activity was observed also during development of insecticides (pulegone (53)/perillaldehyde) [260].
Of note, essential oil components of the thymol (61) and carvacrol (72) type can act as antagonists, as several essential oils showed lower activity than their single monoterpenic components [281]. The review of Bassolé and Juliani [439] showed some examples of synergic, additive or even antagonistic activity of well-known components of essential oils in different bacterial species.
Carvacrol (72) and thymol (61) are often mentioned as inhibitors of growth of food-borne pathogens. These pathogens are represented for example by different strains of Salmonella, Shigella, E. coli or Clostridium. The activity of the essential oils of Z. tenuior and Z. clinopodioides against food-borne bacteria has been proven by Aliakbarlu and Shameli [426]. Together with the results of experiments on the antiradical activity of Z. clinopodioides essential oil, which showed better activity than Z. tenuior [426], Z. clinopodioides essential oils can be seen as promising food preservatives. This observation is supported by some other reports that examined the single components identified in Ziziphora essential oils (Table 3).
The hypolipidemic activity of aromatic water obtained by mixing the Z. tenuior essential oil in water was proven in tests on cholesterol-fed rabbits. However, the levels of measured parameters of hypercholesterolemia were not restored to basal levels [202]. Several patent applications cover the usage of Ziziphora in the treatment of some cardiovascular diseases. It is clear that the components of essential oils obtained from Ziziphora species can affect the cardiovascular system, as visible from data reviewed in Table 3. The cardiovascular activities of thymol (61), carvacrol (72), limonene (38), α-terpineol (71), terpinen4-ol (70), linalool (66) and menthol (56) were reviewed by Santos et al. [221]; however, this review examined a limited number of literature sources. The effects of linalool (66) were tested in a human study, and the activity of several compounds (72, 38, 56, 61, 70 and 71) was examined in animal studies.
Further, linalool (66) and 1,8-cineol (72) showed hypocholesterolemic activity via inhibition of HMG-CoA reductase and inhibition of cholesterol synthesis [318,319]. Endo-borneol (68) exerts a vasorelaxant effect on rat thoracic aorta artery rings [330] and terpinen-4-ol (70) has a relaxant effect on vascular smooth muscle [332].
Several components of Ziziphora essential oils were tested and found to possess antioxidant activity, proven in both in vitro and in vivo assays. For example, monoterpenic α-terpinene (36), terpinolene (37) [217,218], thymol (62) [293], borneol (67) [324], carvacrol (73) [273,294,297,299], and sesquiterpenic caryophylene (91) [392] were found to possess antioxidant activity. The antioxidant activity of Lamiaceae essential oils is known, so they can be used in their entirety or their single compounds can be used as food preservatives; moreover, their antibacterial activity and relative non-toxicity makes them more beneficial than some synthetic antioxidants.

Potential Toxicity

Monoterpenic pulegone (53) is present in many Lamiaceae plants. It is commonly connected with potential toxic effect of so called pennyroyal oil. In high doses, it can cause hepatic failure, central nervous system toxicity, gastritis, renal and pulmonary toxicity, and, in very serious cases, death [451,452]. Assays carried out on mice showed its hepatotoxicity and pulmonary toxicity [451,453]. The toxic potential of pulegone (53) is connected to its extensive metabolism in liver, which includes its oxidation to menthofuran, p‑cresol and other compounds. These compounds can be further metabolized and cause depletion of glutathione; then, they can covalently bind to proteins and modify their function, causing cell injury [454].

3. Conclusions

The traditional medicine of Kazakhstan uses Ziziphora species (Lamiaceae) to combat several diseases. Especially, Z. bungeana Lam. and Z. clinopodioides Lam. are used for the treatment of illnesses connected with cardiovascular system or to combat different infections. We gathered information about four Kazakh Ziziphora species, their traditional utilization and the compounds identified in extracts obtained from these plants. This review presented information about each compound and their bioactivities. We can conclude that as a typical example of the Lamiaceae family, phytochemicals present in Ziziphora are represented especially by monoterpenic essential oil, phenolic substances belonging to the flavonoids and phenolic acids, and triterpenes. The presence of these particular compounds with confirmed activity can be seen as proof of the traditional use and validation of numerous patent applications. We hope that the review on the compounds isolated from Ziziphora, their medicinal uses and published patents will draw the attention of scientists to this very interesting plant with high medicinal potential.

Acknowledgments

Thanks to kontroluje.me for English language corrections.

Author Contributions

K.Š. and M.M. performed the literature search, wrote the manuscript and provided the final corrections. K.Z., Z.S., G.I., L.I. performed the literature search and analyzed sources in Russian language. M.Ž. performed search and provided the final corrections.

Conflicts of Interest

The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

References

  1. Bimursaev, A.A. Fitochemitscheskoe Izutchenie Zizifory bungovskoj (Phytochemical Study of Ziziphora bungeana). Dissertation Thesis, Khakh National Medical University, Alma-Ata, Russia, 1985. [Google Scholar]
  2. Xi-wen, L.; Hedge, I.C. Lamiaceae. In Flora of China; Xiwen, Z.W., Raven, P.H., Eds.; Science Press: Beijing, China; Missouri Botanical Garden Press: St. Louis, MO, USA, 1994; Volume 17. [Google Scholar]
  3. Pavlov, N.V. Flora Kazakhstan; Academia nauk KazSSR: Almaty, Russia, 1964. [Google Scholar]
  4. Furukawa, M.; Oikawa, N.; Imohata, T.; Makino, M.; Ogawa, S.; Iida, T.; Fujimoto, Y.; Kitanaka, S. Monoterpene Glucosides from Ziziphora clinopodioides (Labiatae). Chem. Pharm. Bull. 2012, 60, 397–401. [Google Scholar] [CrossRef] [PubMed]
  5. Tian, S.; Shi, Y.; Zhou, X.; Ge, L.; Upur, H. Total polyphenolic (flavonoids) content and antioxidant capacity of different Ziziphora clinopodioides Lam. Extracts. Pharmacog. Mag. 2011, 7, 65–68. [Google Scholar]
  6. Baytop, T.; Turkiyede, B.; Tedavi, I.U. Yayinlari. Eczacilik Fak 1996, 40, 444. [Google Scholar]
  7. Masrournia, M.; Shams, A. Elemental Determination and Essential Oil Composition of Ziziphora clinopodioides and Consideration of its Antibacterial Effects. Asian J. Chem. 2013, 25, 6553–6556. [Google Scholar]
  8. Beikmohammadi, M. The Evaluation of Medicinal Properties of Ziziphora clinopodioides. World Appl. Sci. J. 2011, 12, 1635–1638. [Google Scholar]
  9. Ozturk, Y.; Aydin, S.; Tecik, B.; Baser, K.H.C. Effects of essential oils from certain Ziziphora species on swimming performance in mice. Phytother. Res. 1995, 9, 225–227. [Google Scholar] [CrossRef]
  10. Tarakci, Z.; Coskun, H.; Tuncturk, Y. Some properties of fresh and ripened herby cheese, a traditional variety produced in Turkey. Food Technol. Biotech. 2004, 42, 47–50. [Google Scholar]
  11. Ozturk, S.; Ercisli, S. Antibacterial activity and chemical constitutions of Ziziphora clinopodioides. Food Control 2007, 18, 535–540. [Google Scholar] [CrossRef]
  12. Ghassemi, N.; Ghanadian, M.; Ghaemmaghami, L.; Kiani, H. Development of a Validated HPLC/Photodiode Array Method for the Determination of Isomenthone in the Aerial Parts of Ziziphora tenuior L. Jundishapur J. Nat. Pharm. Prod. 2013, 8, 180–186. [Google Scholar] [CrossRef] [PubMed]
  13. Sezik, E.; Yesilada, E.; Shadidoyatov, H.; Kulivey, Z.; Nigmatullaev, A.M.; Aripov, H.N.; Takaishi, Y.; Takeda, Y.; Honda, G. Folk medicine in Uzbekistan I. Toshkent, Djizzax, and Samarqand provinces. J. Ethnopharmacol. 2004, 92, 197–207. [Google Scholar] [CrossRef] [PubMed]
  14. Ajiaikebaier, A.; Shi, H.; Abuduwufuer, R. Preparation and Use of Ziziphora General Flavone. Chinese Patent CN 101513448 B, 1 August 2012. [Google Scholar]
  15. Ding, W.; Yang, T.; Liu, F.; Tian, S. Effect of different growth stages of Ziziphora clinopodioides Lam. on its chemical composition. Pharmacog. Mag. 2014, 10. [Google Scholar] [CrossRef]
  16. Razmjoue, D.; Zarei, Z. Study on the ecological specifications effects (climate and height) on chemical compounds of Ziziphora medicinal plant essential oil (Ziziphora clinopodioides Lam.) in Fars province, Iran. J. Chem. Biol. Phys. Sci. 2015, 5, 3049–3066. [Google Scholar]
  17. Jamzad, M.; Jamzad, Z.; Mokhber, F.; Ziareh, S.; Yari, M. Variation in essential oil composition of Mentha longifolia var. chlorodichtya Rech.f. and Ziziphora clinopodiodes Lam. growing in different habitats. J. Med. Plant Res. 2013, 7, 1618–1623. [Google Scholar]
  18. Sonboli, A.; Atri, M.; Shafiei, S. Intraspecific variability of the essential oil of Ziziphora clinopodioides ssp. rigida from Iran. Chem. Biodivers. 2010, 7, 1784–1789. [Google Scholar] [CrossRef] [PubMed]
  19. Khodaverdi-Samani, H.; Pirbalouti, A.G.; Shirmardi, H.-A.; Malekpoor, F. Chemical composition of essential oils of Ziziphora clinopodioides Lam. (endemic Iranian herb) collected from different natural habitats. Indian J. Trad. Know. 2015, 14, 57–62. [Google Scholar]
  20. Jeppesen, A.S.; Soelberg, J.; Jäger, A.K. Antibacterial and COX-1 Inhibitory Effect of Medicinal Plants from the Pamir Mountains, Afghanistan. Plants 2012, 1, 74–81. [Google Scholar] [CrossRef] [PubMed]
  21. Salehi, P.; Sonboli, A.; Eftekhari, F.; Nejad-Ebrahimi, S.; Yousefzadi, M. Essential Oil Composition, Antibacterial and Antioxidant Activity of the Oil and Various Extracts of Ziziphora clinopodioides subsp. rigida (BOISS.) RECH.f. from Iran. Biol. Pharm. Bull. 2005, 10, 1892–1896. [Google Scholar] [CrossRef]
  22. Mahboubi, A.; Kamalinejad, M.; Ayatollahi, A.M.; Babaeian, M. Total phenolic content and antibacterial activity of five plants of Labiatae against four foodborne and some other bacteria. Iranian J. Pharm. Res. 2014, 13, 559–566. [Google Scholar]
  23. Amini-Shirazi, N.; Hoseini, A.; Rajnbar, A.; Mohammadirad, A.; Khoshakhlagh, P.; Yasa, N.; Abdollahi, M. Inhibition of Tumor Necrosis Factor and Nitrosative/Oxidative Stresses by Ziziphora Clinopodioides (Kahlioti); A Molecular Mechanism of Protection Against Dextran Sodium Sulfate-Induced Colitis in Mice. Toxicol. Mech. Methods 2009, 19, 183–189. [Google Scholar] [CrossRef] [PubMed]
  24. Ghafari, H.; Yasa, N.; Mohammadirad, A.; Dehghan, G.; Zamani, M.J.; Nikfar, S.; Khorasani, R.; Minaie, B.; Abdollahi, M. Protection by Ziziphora clinopoides of acetic acid-induced toxic bowel inflammation through reduction of cellular lipid peroxidation and myeloperoxidase activity. Hum. Exp. Toxicol. 2006, 25, 325–332. [Google Scholar] [CrossRef] [PubMed]
  25. Azadmehr, A.; Latifi, R.; Mosalla, S.; Hajiaghaee, R.; Shahnazi, M. Immunomodulatory effects of Ziziphora tenuior L. extract on the dendritic cells. Daru 2014, 22, 63. [Google Scholar] [CrossRef] [PubMed]
  26. Ghahhari, J.; Vaezi, G.; Shariatifar, N.; Zendehdel, K.M. The study of hydroalcoholic extract of Ziziphora tenuior on visceral pain with writhing test in mice. Horizon. Med. Sci. 2009, 15, 24–29. [Google Scholar]
  27. Ghazanfari, T.; Yaraee, R.; Shams, J.; Rahmati, B.; Radjabian, T.; Hakimzadeh, H. Cytotoxic effect of four herbal medicines on gastric cancer (AGS) cell line. Food Agric. Immunol. 2013, 24. [Google Scholar] [CrossRef]
  28. Entezary, A.; Neamatshahi, M.M.; Khodaparast, M.H.H.; Farjam, M.K.N.; Nematshahi, N.; Mohammadi, M. The effects of adding extracts of Ziziphora (Ziziphora tenuir) as flavoring to chewing gums and the study of the release of caffeine from these extracts. Eur. J. Exp. Biol. 2013, 3, 307–312. [Google Scholar]
  29. Sadeghi, B.; Gholamhoseinpoor, F. A study on the stability and green synthesis of silver nanoparticles using Ziziphora tenuior (Zt) extract at room temperature. Spectrosc. Acta Pt. A Mol. Biomol. Spectr. 2015, 134, 310–315. [Google Scholar] [CrossRef] [PubMed]
  30. Weijun, Y.; Bo, C.; Yan, M.; Tuerxunjiang, D.; Wencai, X.; Chong, L.; Jiang, H.; Hairula, M.; Tuhehongda, Z. Compound Ziziphora bungeana Capsule, and Preparation Method and Application Thereof. Chinese Patent CN102895304 (A), 30 January 2013. [Google Scholar]
  31. Ajiaikebaier, A.; Shi, H.; Abuduwufuer, R. Preparation and Use of Ziziphora General Flavone. CN 101513448 A, 26 August 2009. [Google Scholar]
  32. Jiang, H.; Yang, W.; Feng, S.; Abudushalamu, M. Ziziphora clinopodioides Lam. Extract and Production Method Thereof and Application Thereof in Cardiovascular Drugs. Chinese Patent CN101623324 (B), 1 February 2012. [Google Scholar]
  33. Yang, W.; Hairula, M.; Chong, L.; Jiang, H. Ziziphora bungeana Dripping Pills, Production Method Thereof and Application of Dripping Pills as Cardiovascular Medicament. Chinese Patent CN102048813 (A), 11 May 2011. [Google Scholar]
  34. Zheng, S.; Meng, X.; Zhu, H.; Xu, M. Traditional Chinese Medicine Compound for Treating Paroxysmal Supraventricular Tachycardia. Chinese Patent CN102861169 (A), 9 January 2013. [Google Scholar]
  35. Bahaerguli, A.; Zhu, X.; Xu, X.; Bao, E. Kazak Medicine Ziziphora clinopodioides Lam. Oral Cavity Spray. Chinese Patent CN101485621 (A), 22 July 2009. [Google Scholar]
  36. Wang, Y.; Ban, X.; He, J.; Huang, B.; Zeng, H.; Jun, T.; Chen, Y. Preparation Method of Ziziphora clinopodioides Volatile Oil and Function Thereof of Preventing and Treating Sclerotinia Rot of Rape. Chinese Patent CN102093932 (B), 14 November 2012. [Google Scholar]
  37. Tian, S.; Zhou, X.; Hammulati, W.; Yu, Q.; Liu, H.; Ge, L. Ziziphora clinopodioides Lam Fingerprint and Establishment Method Thereof. Chinese Patent CN 102662019 (A), 12 September 2012. [Google Scholar]
  38. Mehmood, R.; Imran, M.; Malik, A.; Tareen, R.B. Ziziphorins A and B. New flavonoids from Ziziphora tenuior. Z. Naturforsch. Sect. B J. Chem. Sci. 2010, 65, 1397–1400. [Google Scholar] [CrossRef]
  39. Senejoux, F.; Demougeot, C.; Kerram, P.; Aisa, H.A.; Berthelot, A.; Bévalot, F.; Girard-Thernier, C. Bioassay-guided isolation of vasorelaxant compounds from Ziziphora clinopodioides Lam. (Lamiaceae). Fitoterapia 2012, 83, 377–382. [Google Scholar] [CrossRef] [PubMed]
  40. Ye, Y.; Liu, B.Y.; Zou, G.; Aisa, H.A. Chemical constituents of Ziziphora clinopodioides. Chem. Nat. Compd. 2012, 48, 681–682. [Google Scholar] [CrossRef]
  41. Nabavi, S.M.; Habtemariam, S.; Daglia, M.; Nabavi, S.F. Apigenin and Breast Cancers: From Chemistry to Medicine. Anti-Cancer Agents Med. Chem. 2015, 15, 728–735. [Google Scholar] [CrossRef]
  42. Bao, Y.Y.; Zhou, S.H.; Fan, J.; Wang, Q.Y. Anticancer mechanism of apigenin and the implications of GLUT-1 expression in head and neck cancers. Future Oncol. 2013, 9, 1353–1364. [Google Scholar] [CrossRef] [PubMed]
  43. Babcook, M.A.; Gupta, S. Apigenin: a promising anticancer agent for the modulation of the insulin-like growth factor (IGF) axis in prostate cancer. Biomed. Res. 2012, 23, 55–68. [Google Scholar]
  44. Shukla, S.; Gupta, S. Apigenin: A Promising Molecule for Cancer Prevention. Pharm. Res. 2010, 27, 962–978. [Google Scholar] [CrossRef] [PubMed]
  45. Lefort, E.C.; Blay, J. Apigenin and its impact on gastrointestinal cancers. Mol. Nutr. Food Res. 2013, 57, 126–144. [Google Scholar] [CrossRef] [PubMed]
  46. Shukla, S.; Gupta, S. Role of apigenin in human health and disease. In Beer in Health and Disease Prevention; Preedy, V.R., Ed.; Academic Press: Burlington, MA, USA, 2009; pp. e202–e216. [Google Scholar]
  47. Nabavi, S.F.; Braidy, N.; Habtemariam, S.; Orhan, I.E.; Daglia, M.; Manayi, A.; Gortzi, O.; Nabavi, S.M. Neuroprotective effects of chrysin: From chemistry to medicine. Neurochem. Int. 2015, 90, 224–231. [Google Scholar] [CrossRef] [PubMed]
  48. Kasala, E.R.; Bodduluru, L.N.; Madana, R.M.; V, A.K.; Gogoi, R.; Barua, C.C. Chemopreventive and therapeutic potential of chrysin in cancer: Mechanistic perspectives. Toxicol. Lett. 2015, 233, 214–225. [Google Scholar] [CrossRef] [PubMed]
  49. Kasala, E.R.; Bodduluru, L.N.; Barua, C.C.; Gogoi, R. Chrysin and its emerging role in cancer drug resistance. Chem.-Biol. Interact. 2015, 236, 7–8. [Google Scholar] [CrossRef] [PubMed]
  50. Liu, Y.; Song, X.; He, J.; Zheng, X.; Wu, H. Synthetic derivatives of chrysin and their biological activities. Med. Chem. Res. 2014, 23, 555–563. [Google Scholar] [CrossRef]
  51. Tuorkey, M.J. Molecular targets of luteolin in cancer. Eur. J. Cancer Prev. 2016, 25, 65–76. [Google Scholar] [CrossRef] [PubMed]
  52. Kapoor, S. Luteolin and its inhibitory effect on tumor growth in systemic malignancies. Exp. Cell Res. 2013, 319, 777–778. [Google Scholar] [CrossRef] [PubMed]
  53. Nabavi, S.F.; Braidy, N.; Gortzi, O.; Sobarzo-Sanchez, E.; Daglia, M.; Skalicka-Woźniak, K.; Nabavi, S.M. Luteolin as an anti-inflammatory and neuroprotective agent: A brief review. Brain Res. Bull. 2015, 119. [Google Scholar] [CrossRef] [PubMed]
  54. Theoharides, T.C. Luteolin as a therapeutic option for multiple sclerosis. J. Neuroinflammation 2009, 6, 29. [Google Scholar] [CrossRef] [PubMed]
  55. Maruoka, H.; Shimoke, K. Mechanisms of neurotrophic activities via low-molecular-weight compounds: Post-transcriptional regulation in PC12 cells and neurons. Clin. Pharmacol. Biopharm. 2013, S1, 003. [Google Scholar] [CrossRef]
  56. Kritas, S.K.; Saggini, A.; Varvara, G.; Murmura, G.; Caraffa, A.; Antinolfi, P.; Toniato, E.; Pantalone, A.; Neri, G.; Frydas, S.; et al. Luteolin inhibits mast cell-mediated allergic inflammation. J. Biol. Reg. Homeos. Ag. 2013, 27, 955–959. [Google Scholar]
  57. Jiang, D.; Li, D.; Wu, W. Inhibitory effects and mechanisms of luteolin on proliferation and migration of vascular smooth muscle cells. Nutrients 2013, 5, 1648–1659. [Google Scholar] [CrossRef] [PubMed]
  58. Xu, T.; Li, D.; Jiang, D. Targeting cell signaling and apoptotic pathways by luteolin: Cardioprotective role in rat cardiomyocytes following ischemia/reperfusion. Nutrients 2012, 4, 2008–2019. [Google Scholar] [CrossRef] [PubMed]
  59. Lopez-Lazaro, M. Distribution and biological activities of the flavonoid luteolin. Mini-Rev. Med. Chem. 2009, 9, 31–59. [Google Scholar] [CrossRef] [PubMed]
  60. Seelinger, G.; Merfort, I.; Schempp, C.M. Anti-oxidant, anti-inflammatory and anti-allergic activities of luteolin. Planta Med. 2008, 74, 1667–1677. [Google Scholar] [CrossRef] [PubMed]
  61. Oganesvan, G.B.; Galstyan, A.M.; Mnatsakanyan, V.A.; Paronikyan, R.V.; Ter-Zakharyan, Y.Z. Phenols and flavonoids of Ziziphora clinopodioides. Khimiya Prirodnykh Soedinenii 1991, 2, 286–287. [Google Scholar]
  62. Gohari, A.R.; Saeidnia, S.; Gohari, M.R.; Moradi-Afrapoli, F.; Malmir, M.; Hadjiakhoondi, A. Bioactive flavonoids from Satureja atropatana Bonge. Nat. Prod. Res. 2009, 23, 1609–1614. [Google Scholar] [CrossRef] [PubMed]
  63. Dugas, A.J.; Castaneda-Acosta, J.; Bonin, G.C.; Price, K.L.; Fischer, N.H.; Winston, G.W. Evaluation of the Total Peroxyl Radical-Scavenging Capacity of Flavonoids: Structure-Activity Relationships. J. Nat. Prod. 2000, 63, 327–331. [Google Scholar] [CrossRef] [PubMed]
  64. Bhat, T.A.; Nambiar, D.; Tailor, D.; Pal, A.; Agarwal, R.; Singh, R.P. Acacetin Inhibits In Vitro and In Vivo Angiogenesis and Downregulates Stat Signaling and VEGF Expression. Cancer Prev. Res. 2013, 6, 1128–1139. [Google Scholar] [CrossRef] [PubMed]
  65. Liu, L.-Z.; Jing, Y.; Jiang, L.L.; Jiang, X.E.; Jiang, Y.; Rojanasakul, Y.; Jiang, B.H. Acacetin inhibits VEGF expression, tumor angiogenesis and growth through AKT/HIF-1α pathway. Biochem. Biophys. Res. Commun. 2011, 413, 299–305. [Google Scholar] [CrossRef] [PubMed]
  66. Kim, C.D.; Cha, J.D.; Li, S.; Cha, I.H. The mechanism of acacetin-induced apoptosis on oral squamous cell carcinoma. Arch. Oral Biol. 2015, 60, 1283–1298. [Google Scholar] [CrossRef] [PubMed]
  67. Shim, H.Y.; Park, J.H.; Paik, H.D.; Nah, S.Y.; Kim, D.S.; Han, Y.S. Acacetin-induced apoptosis of human breast cancer MCF-7 cells involves caspase cascade, mitochondria-mediated death signaling and SAPK/JNK1/2-c-Jun activation. Mol. Cells 2007, 24, 95–104. [Google Scholar] [PubMed]
  68. Singh, R.P.; Agrawal, P.; Yim, D.; Agarwal, C.; Agarwal, R. Acacetin inhibits cell growth and cell cycle progression, and induces apoptosis in human prostate cancer cells: Structure-activity relationship with linarin and linarin acetate. Carcinogenesis 2005, 26, 845–854. [Google Scholar] [CrossRef] [PubMed]
  69. Pan, M.H.; Lai, C.S.; Hsu, P.C.; Wang, Y.J. Acacetin Induces Apoptosis in Human Gastric Carcinoma Cells Accompanied by Activation of Caspase Cascades and Production of Reactive Oxygen Species. J. Agric. Food Chem. 2005, 53, 620–630. [Google Scholar] [CrossRef] [PubMed]
  70. Hsu, Y.L.; Kuo, P.L.; Liu, C.F.; Lin, C.C. Acacetin-induced cell cycle arrest and apoptosis in human non-small cell lung cancer A549 cells. Cancer Lett. 2004, 212, 53–60. [Google Scholar] [CrossRef] [PubMed]
  71. Warat, M.; Szliszka, E.; Korzonek-Szlacheta, I.; Król, W.; Czuba, Z.P. Chrysin, apigenin and acacetin inhibit Tumor Necrosis Factor-related apoptosis-inducing ligand receptor-1 (TRAIL-R1) on activated RAW264.7 macrophages. Int. J. Mol. Sci. 2014, 15, 11510–11522. [Google Scholar] [CrossRef] [PubMed]
  72. Kim, H.R.; Park, C.G.; Jung, J.Y. Acacetin (5,7-dihydroxy-4´-methoxyflavone) exhibits in vitro and in vivo anticancer activity through the suppression of NF-κB/Akt signaling in prostate cancer cells. Int. J. Mol. Med. 2014, 33, 317–324. [Google Scholar] [PubMed]
  73. Jung, S.K.; Kim, J.E.; Lee, S.Y.; Lee, M.H.; Byun, S.; Kim, Y.A.; Lim, T.G.; Reddy, K.; Huang, Z.; Bode, A.M.; et al. The P110 subunit of PI3-K is a therapeutic target of acacetin in skin cancer. Carcinogenesis 2014, 35, 123–130. [Google Scholar] [CrossRef] [PubMed]
  74. Horibe, I.; Satoh, Y.; Shiota, Y.; Kumagai, A.; Horike, N.; Takemori, H.; Uesato, S.; Sugie, S.; Obata, K.; Kawahara, H.; et al. Induction of melanogenesis by 4´-O-methylated flavonoids in B16F10 melanoma cells. J. Nat. Med. 2013, 67, 705–710. [Google Scholar] [CrossRef] [PubMed]
  75. Ninomiya, M.; Nishida, K.; Tanaka, K.; Watanabe, K.; Koketsu, M. Structure-activity relationship studies of 5,7‑dihydroxyflavones as naturally occurring inhibitors of cell proliferation in human leukemia HL-60 cells. J. Nat. Med. 2013, 67, 460–467. [Google Scholar] [CrossRef] [PubMed]
  76. Boussouar, A.; Barette, C.; Nadon, R.; Saint-Léger, A.; Broucqsault, N.; Ottaviani, A.; Firozhoussen, A.; Lu, Y.; Lafanechère, L.; Gilson, E.; et al. Acacetin and chrysin, two polyphenolic compounds, alleviate telomeric position effect in human cells. Mol. Ther. Nucleic Acids 2013, 2, e116. [Google Scholar] [CrossRef] [PubMed]
  77. Fong, Y.; Shen, K.H.; Chiang, T.A.; Shih, Y.W. Acacetin inhibits TPA-induced MMP-2 and u-PA expressions of human lung cancer cells through inactivating JNK signaling pathway and reducing binding activities of NF-κB and AP-1. J. Food Sci. 2010, 75, 30–38. [Google Scholar] [CrossRef] [PubMed]
  78. Shen, K.H.; Hung, S.H.; Yin, L.T.; Huang, C.S.; Chao, C.H.; Liu, C.L.; Shih, Y.W. Acacetin, a flavonoid, inhibits the invasion and migration of human prostate cancer DU145 cells via inactivation of the p38 MAPK signaling pathway. Mol. Cell. Biochem. 2010, 333, 279–291. [Google Scholar] [CrossRef] [PubMed]
  79. Patel, K.; Gadewar, M.; Tahilyani, V.; Patel, D.K. A review on pharmacological and analytical aspects of diosmetin: A concise report. Chin. J. Integr. Med. 2013, 19, 792–800. [Google Scholar] [CrossRef] [PubMed]
  80. Tian, S.; Yu, Q.; Wang, D.; Upur, H. Development of a rapid resolution liquid chromatography-diode array detector method for the determination of three compounds in Ziziphora clinopodioides Lam from different origins of Xinjiang. Pharmacog. Mag. 2012, 8, 280–284. [Google Scholar]
  81. Abdurrazak, M.; Rao, M.U.S.; Ado, A.B.; Mohd, K.S.; Thant, Z. Some natural products and their secondary metabolites attributed towards diabetic cure: a review. Int. J. Pharm. Pharm. Sci. 2015, 7, 22–28. [Google Scholar]
  82. Bogucka-Kocka, A.; Wozniak, M.; Feldo, M.; Kockic, J.; Szewczyk, K. Diosmin—Isolation techniques, determination in plant material and pharmaceutical formulations, and clinical use. Nat. Prod. Commun. 2013, 8, 545–550. [Google Scholar] [PubMed]
  83. Yoon, Y.P.; Lee, H.J.; Kim, Y.H.; Luyen, B.T.T.; Hong, J.H.; Lee, C.J. Effects of cynaroside, cynarin and linarin on secretion, production and gene expression of airway MUC5AC mucin in NCI-H292 cells. Nat. Prod. Sci. 2015, 21, 59–65. [Google Scholar]
  84. Kim, S.J.; Cho, H.I.; Kim, S.J.; Park, J.H.; Kim, J.S.; Kim, Y.H.; Lee, S.K.; Kwak, J.H.; Lee, S.M. Protective effect of linarin against d-galactosamine and lipopolysaccharide-induced fulminant hepatic failure. Eur. J. Pharmacol. 2014, 738, 66–73. [Google Scholar] [CrossRef] [PubMed]
  85. Sivashanmugam, M.; Raghunath, C.; Vetrivel, U. Virtual screening studies reveal linarin as a potential natural inhibitor targeting CDK4 in retinoblastoma. J. Pharmacol. Pharmacother. 2013, 4, 256–264. [Google Scholar] [PubMed]
  86. Lou, H.; Fan, P.; Perez, R.G.; Lou, H. Neuroprotective effects of linarin through activation of the PI3K/Akt pathway in amyloid-β-induced neuronal cell death. Bioorg. Med. Chem. 2011, 19, 4021–4027. [Google Scholar] [CrossRef] [PubMed]
  87. Fan, P.; Hay, A.E.; Marston, A.; Hostettmann, K. Acetylcholinesterase-Inhibitory Activity of Linarin from Buddleja davidii, Structure-Activity Relationships of Related Flavonoids, and Chemical Investigation of Buddleja nitida. Pharm. Biol. 2008, 46, 596–601. [Google Scholar] [CrossRef]
  88. Han, S.; Sung, K.H.; Yim, D.; Lee, S.; Lee, C.K.; Ha, N.J.; Kim, K. The effect of linarin on LPS-induced cytokine production and nitric oxide inhibition in murine macrophages cell line RAW264.7. Arch. Pharmacal. Res. 2002, 25, 170–177. [Google Scholar] [CrossRef]
  89. Wu, J.; Feng, J.Q.; Zhao, W.M. A new lignan and anti-inflammatory flavonoids from Kerria japonica. J. Asian Nat. Prod. Res. 2008, 10, 435–438. [Google Scholar] [CrossRef] [PubMed]
  90. Fernandez, S.P.; Wasowski, C.; Loscalzo, L.M.; Granger, R.E.; Johnston, G.A.; Paladini, A.C.; Marder, M. Central nervous system depressant action of flavonoid glycosides. Eur. J. Pharmacol. 2006, 539, 168–176. [Google Scholar] [CrossRef] [PubMed]
  91. Fernandez, S.; Wasowski, C.; Paladini, A.; Marder, M. Sedative and sleep-enhancing properties of linarin, a flavonoid-isolated from Valeriana officinalis. Pharmacol. Biochem. Behav. 2004, 77, 399–404. [Google Scholar] [CrossRef] [PubMed]
  92. Yu, J.; Weiwer, M.; Linhardt, R.J.; Dordick, J.S. The role of the methoxyphenol apocynin, a vascular NADPH oxidase inhibitor, as a chemopreventative agent in the potential treatment of cardiovascular diseases. Curr. Vasc. Pharmacol. 2008, 6, 204–217. [Google Scholar] [CrossRef] [PubMed]
  93. ‘t Hart, B.A.; Copray, S.; Philippens, I. Apocynin, a low molecular oral treatment for neurodegenerative disease. BioMed. Res. Int. 2014, 298020. [Google Scholar] [CrossRef]
  94. Pakniyat, E.; Mousavi, M. Improvement of GC-MS Analysis of Shahrbabak Ziziphora tenuior Essential Oil by Using Multivariate Curve Resolution Approaches. J. Chin. Chem. Soc. 2014, 61, 649–658. [Google Scholar] [CrossRef]
  95. Zhu, T.H.; Yu, Y.Y.; Cao, S.W. Tyrosinase inhibitory effects and antioxidant properties of paeonol and its analogues. Food Sci. Technol. Res. 2013, 19, 609–615. [Google Scholar] [CrossRef]
  96. Kim, M.G.; Yang, J.Y.; Lee, H.S. Acaricidal Potentials of Active Properties Isolated from Cynanchum paniculatum and Acaricidal Changes by Introducing Functional Radicals. J. Agric. Food Chem. 2013, 61, 7568–7573. [Google Scholar] [CrossRef] [PubMed]
  97. Benalla, W.; Bellahcen, S.; Bnouham, M. Antidiabetic medicinal plants as a source of alpha glucosidase inhibitors. Curr. Diabetes Rev. 2010, 6, 247–254. [Google Scholar] [CrossRef] [PubMed]
  98. Su, P.; Shi, Y.; Wang, J.; Shen, X.; Zhang, J. Anticancer Agents Derived from Natural Cinnamic Acids. Anti-Cancer Agents Med. Chem. 2015, 15, 980–987. [Google Scholar] [CrossRef]
  99. Fuentes, E.; Palomo, I. Mechanisms of endothelial cell protection by hydroxycinnamic acids. Vasc. Pharmacol. 2014, 63, 155–161. [Google Scholar] [CrossRef] [PubMed]
  100. Magnani, C.; Isaac, V.L.B.; Correa, M.A.; Salgado, H. Caffeic acid: A review of its potential use in medications and cosmetics. Anal. Meth. 2014, 6, 3203–3210. [Google Scholar] [CrossRef]
  101. Bhullar, K.S.; Lassalle-Claux, G.; Touaibia, M.; Rupasinghe, H.P. Antihypertensive effect of caffeic acid and its analogs through dual renin-angiotensin-aldosterone system inhibition. Eur. J. Pharmacol. 2014, 730, 125–132. [Google Scholar] [CrossRef] [PubMed]
  102. Li, Q.L.; Li, B.G.; Zhang, Y.; Gao, X.P.; Li, C.Q.; Zhang, G.L. Three angiotensin-converting enzyme inhibitors from Rabdosia coetsa. Phytomedicine 2008, 15, 386–388. [Google Scholar] [CrossRef] [PubMed]
  103. Silva, T.; Borges, F.; Edraki, N.; Alizadeh, M.; Miri, R.; Saso, L.; Firuzi, O. Hydroxycinnamic acid as a novel scaffold for the development of cyclooxygenase-2 inhibitors. RSC Adv. 2015, 5, 58902–58911. [Google Scholar] [CrossRef]
  104. Chiang, Y.M.; Lo, C.P.; Chen, Y.P.; Wang, S.Y.; Yang, N.S.; Kuo, Y.H.; Shyur, L.F. Ethyl caffeate suppresses NF-κB activation and its downstream inflammatory mediators, iNOS, COX-2, and PGE2 in vitro or in mouse skin. Br. J. Pharmacol. 2005, 146, 352–363. [Google Scholar] [CrossRef] [PubMed]
  105. da Cunha, F.M.; Duma, D.; Assreuy, J.; Buzzi, F.C.; Niero, R.; Campos, M.M.; Calixto, J.B. Caffeic Acid Derivatives: In Vitro and In Vivo Anti-inflammatory Properties. Free Radic. Res. 2004, 38, 1241–1253. [Google Scholar] [CrossRef] [PubMed]
  106. Williams, L.K.; Li, C.; Withers, S.G.; Brayer, G.D. Order and Disorder: Differential Structural Impacts of Myricetin and Ethyl Caffeate on Human Amylase, an Antidiabetic Target. J. Med. Chem. 2012, 55, 10177–10186. [Google Scholar] [CrossRef] [PubMed]
  107. Yokoyama, T.; Kosaka, Y.; Mizuguchi, M. Inhibitory Activities of Propolis and Its Promising Component, Caffeic Acid Phenethyl Ester, against Amyloidogenesis of Human Transthyretin. J. Med. Chem. 2014, 57, 8928–8935. [Google Scholar] [CrossRef] [PubMed]
  108. Wang, J.; Gu, S.S.; Pang, N.; Wang, F.Q.; Pang, F.; Cui, H.S.; Wu, X.Y.; Wu, F.A. Alkyl caffeates improve the antioxidant activity, antitumor property and oxidation stability of edible oil. PLoS ONE 2014, 9, e95909. [Google Scholar] [CrossRef] [PubMed]
  109. Hradkova, I.; Merkl, R.; Smidrkal, J.; Kyselka, J.; Filip, V. Antioxidant effect of mono- and dihydroxyphenols in sunflower oil with different levels of naturally present tocopherols. Eur. J. Lipid Sci. Technol. 2013, 115, 747–755. [Google Scholar] [CrossRef] [PubMed]
  110. Garrido, J.; Gaspar, A.; Garrido, E.; Miri, R.; Tavakkoli, M.; Pourali, S.; Saso, L.; Borges, F.; Firuzi, O. Alkyl esters of hydroxycinnamic acids with improved antioxidant activity and lipophilicity protect PC12 cells against oxidative stress. Biochimie 2012, 94, 961–967. [Google Scholar] [CrossRef] [PubMed]
  111. Frega, N.G.; Boselli, E.; Bendia, E.; Minardi, M.; Benedetti, A. Ethyl caffeoate: Liquid chromatography-tandem mass spectrometric analysis in Verdicchio wine and effects on hepatic stellate cells and intracellular peroxidation. Anal. Chim. Acta 2006, 563, 375–381. [Google Scholar] [CrossRef]
  112. Lee, H.N.; Kim, J.K.; Kim, J.H.; Lee, S.J.; Ahn, E.K.; Oh, J.S.; Seo, D.W. A mechanistic study on the anti-cancer activity of ethyl caffeate in human ovarian cancer SKOV-3 cells. Chem.-Biol. Interact. 2014, 219, 151–158. [Google Scholar] [CrossRef] [PubMed]
  113. Amoah, S.K.; Sandjo, L.P.; Kratz, J.M.; Biavatti, M.W. Rosmarinic Acid—Pharmaceutical and Clinical Aspects. Planta Med. 2016, 82, 388–406. [Google Scholar] [CrossRef] [PubMed]
  114. Nabavi, S.F.; Tenore, G.C.; Daglia, M.; Tundis, R.; Loizzo, M.R.; Nabavi, S.M. The Cellular Protective Effects of Rosmarinic Acid: From Bench to Bedside. Curr. Neurovasc. Res. 2015, 12, 98–105. [Google Scholar] [CrossRef] [PubMed]
  115. Kim, G.D.; Park, Y.S.; Jin, Y.H.; Park, C.S. Production and applications of rosmarinic acid and structurally related compounds. Appl. Microbiol. Biotechnol. 2015, 99, 2083–2092. [Google Scholar] [CrossRef] [PubMed]
  116. Hossan, M.S.; Rahman, S.; Bashar, A.B.M.A.; Rahmatullah, M. Rosmarinic acid: A review of its anticancer action. World J. Pharm. Pharm. Sci. 2014, 3, 57–70. [Google Scholar]
  117. Juurlink, B.H.J.; Azouz, H.J.; Aldalati, A.M.Z.; AlTinawi, B.M.; Ganguly, P. Hydroxybenzoic acid isomers and the cardiovascular system. Nutr. J. 2014, 13, 63. [Google Scholar] [CrossRef] [PubMed]
  118. Mahdi, J.; Al-Musayeib, N.; Mahdi, E.; Pepper, C. Pharmacological Importance of Simple Phenolic Compounds on Inflammation, Cell Proliferation and Apoptosis with a Special Reference to β-d-Salicin and Hydroxybenzoic Acid. Eur. J. Inflamm. 2013, 11, 327–336. [Google Scholar]
  119. Opgrande, J.L.; Brown, E.E.; Hesser, M.; Andrews, J. Benzoic acid. In Kirk-Othmer Encyclopedia of Chemical Technology, 5th ed.; Seidel, A., Ed.; John Wiley & Sons: Hoboken, New Jersey, NJ, USA, 2004; Volume 3, pp. 625–637. [Google Scholar]
  120. Ina, H.; Yamada, K.; Matsumoto, K.; Miyazaki, T. Effects of benzyl glucoside and chlorogenic acid from Prunus mume on angiotensin converting enzyme, aldosterone and corticosterone levels in rat plasma. Nat. Med. 2003, 57, 178–180. [Google Scholar]
  121. Luyen, B.T.T.; Tai, B.H.; Thao, N.P.; Cha, J.Y.; Lee, H.Y.; Lee, Y.M.; Kim, Y.H. Anti-inflammatory components of Chrysanthemum indicum flowers. Bioorg. Med. Chem. Lett. 2015, 25, 266–269. [Google Scholar] [CrossRef] [PubMed]
  122. Mook-Jung, I.; Kim, H.F.; Wenzhe, T.; Tezuka, Y.; Kadota, S.; Nishijo, H.; Jung, M.W. Neuroprotective effects of constituents of the oriental crude drugs, Rhodiola sacra, R. sachalinensis and Tokaku-joki-to, against β-amyloid toxicity, oxidative stress and apoptosis. Biol. Pharm. Bull. 2002, 25, 1101–1104. [Google Scholar] [CrossRef] [PubMed]
  123. Fukuda, T.; Ito, H.; Mukainaka, T.; Tokuda, H.; Nishino, H.; Yoshida, T. Anti-tumor promoting effect of glycosides from Prunus persica seeds. Biol. Pharm. Bull. 2003, 26, 271–273. [Google Scholar] [CrossRef] [PubMed]
  124. Wang, W.; Chen, W.; Yang, Y.; Liu, T.; Yang, H.; Xin, Z. New Phenolic Compounds from Coreopsis tinctoria Nutt. and Their Antioxidant and Angiotensin I-Converting Enzyme Inhibitory Activities. J. Agric. Food Chem. 2015, 63, 200–207. [Google Scholar] [CrossRef] [PubMed]
  125. Nguyen, V.T.; Nguyen, P.T.; Dat, L.D.; Huong, P.T.; Lee, S.H.; Jang, H.D.; Cuong, N.X.; Nam, N.H.; Kiem, P.V.; Minh, C.V.; et al. Two new naphthalene glucosides and other bioactive compounds from the carnivorous plant Nepenthes mirabilis. Arch. Pharmacal. Res. 2015, 38, 1774–1782. [Google Scholar]
  126. Du, S.S.; Yang, K.; Wang, C.F.; You, C.X.; Geng, Z.F.; Guo, S.S.; Deng, Z.W.; Liu, Z.L. Chemical Constituents and Activities of the Essential Oil from Myristica fragrans against Cigarette Beetle Lasioderma serricorne. Chem. Biodivers. 2014, 11, 1449–1456. [Google Scholar] [CrossRef] [PubMed]
  127. Do Nascimento, A.F.; da Camara, C.A.; de Moraes, M.M.; Ramos, C. Essential oil composition and acaricidal activity of Schinus terebinthifolius from Atlantic forest of Pernambuco, Brazil against Tetranychus urticae. Nat. Prod. Commun. 2012, 7, 129–132. [Google Scholar] [PubMed]
  128. Duman, A.D.; Telci, I.; Dayisoylu, K.S.; Digrak, M.; Demirtas, I.; Alma, M.H. Evaluation of bioactivity of linalool-rich essential oils from Ocimum basilicum and Coriandrum sativum varieties. Nat. Prod. Commun. 2010, 5, 969–974. [Google Scholar] [PubMed]
  129. Marongiu, B.; Piras, A.; Porcedda, S.; Tuveri, E.; Sanjust, E.; Meli, M.; Sollai, F.; Zucca, P.; Rescigno, A. Supercritical CO2 Extract of Cinnamomum zeylanicum: Chemical Characterization and Antityrosinase Activity. J. Agric. Food Chem. 2007, 55, 10022–10027. [Google Scholar] [CrossRef] [PubMed]
  130. Bahramsoltani, R.; Farzaei, M.H.; Farahani, M.S.; Rahimi, R. Phytochemical constituents as future antidepressants: A comprehensive review. Rev. Neurosci. 2015, 26, 699–719. [Google Scholar] [CrossRef] [PubMed]
  131. Freires, I.A.; Denny, C.; Benso, B.; de Alencar, S.M.; Rosalen, P.L. Antibacterial activity of essential oils and their isolated constituents against cariogenic bacteria: A systematic review. Molecules 2015, 20, 7329–7358. [Google Scholar] [CrossRef] [PubMed]
  132. Langeveld, W.T.; Veldhuizen, E.J.A.; Burt, S.A. Synergy between essential oil components and antibiotics: A review. Cr. Rev. Microbiol. 2014, 40, 76–94. [Google Scholar] [CrossRef] [PubMed]
  133. Srinivasan, K. Antioxidant Potential of Spices and Their Active Constituents. Cr. Rev. Food Sci. Nutr. 2014, 54, 352–372. [Google Scholar] [CrossRef] [PubMed]
  134. Kamatou, G.P.; Vermaak, I.; Viljoen, A.M. Eugenol—From the remote Maluku islands to the international market place: A review of a remarkable and versatile molecule. Molecules 2012, 17, 6953–6981. [Google Scholar] [CrossRef] [PubMed]
  135. Senejoux, F.; Girard, C.; Kerram, P.; Aisa, H.A.; Berthelot, A.; Bévalot, F.; Demougeot, C. Mechanisms of vasorelaxation induced by Ziziphora clinopodioides Lam. (Lamiaceae) extract in rat thoracic aorta. J. Ethnopharmacol. 2010, 132, 268–273. [Google Scholar] [CrossRef] [PubMed]
  136. Cushnie, T.P.; Lamb, A.J. Antimicrobial activity of flavonoids. Int. J. Antimicrob. Agents 2005, 26, 343–356. [Google Scholar] [CrossRef] [PubMed]
  137. Hosek, J.; Smejkal, K. Flavonoids as anti-inflammatory agents. In Encyclopedia of Inflammatory Diseases; Parnham, M.J., Ed.; Birkhauser Verlag AG: Basel, Switzerland, 2016; In press. [Google Scholar]
  138. Pan, M.H.; Lai, C.S.; Ho, C.T. Anti-inflammatory activity of dietary flavonoids. Food Funct. 2010, 1, 15–31. [Google Scholar] [CrossRef] [PubMed]
  139. Lozano-Mena, G.; Sanchez-Gonzalez, M.; Juan, M.E.; Planas, J.M. Maslinic acid, a natural phytoalexin-type triterpene from olives—A promising nutraceutical? Molecules 2014, 19, 11538–11559. [Google Scholar] [CrossRef] [PubMed]
  140. Rodriguez-Rodriguez, R. Oleanolic Acid and Related Triterpenoids from Olives on Vascular Function: Molecular Mechanisms and Therapeutic Perspectives. Curr. Med. Chem. 2015, 22, 1414–1425. [Google Scholar] [CrossRef] [PubMed]
  141. Paszel-Jaworska, A.; Romaniuk, A.; Rybczynska, M. Molecular Mechanisms of Biological Activity of Oleanolic Acid—A Source of Inspiration for A New Drugs Design. Mini-Rev. Org. Chem. 2014, 11, 330–342. [Google Scholar] [CrossRef]
  142. Kashyap, D.; Tuli, H.S.; Sharma, A.K. Ursolic acid (UA): A metabolite with promising therapeutic potential. Life Sci. 2016, 146, 201–213. [Google Scholar] [CrossRef] [PubMed]
  143. Tian, S.; Shi, Y.; Yu, Q.; Upur, H. Determination of oleanolic acid and ursolic acid contents in Ziziphora clinopodioides Lam. by HPLC method. Pharmacog. Mag. 2010, 6, 116–119. [Google Scholar] [CrossRef] [PubMed]
  144. Sánchez-Quesada, C.; López-Biedma, A.; Warleta, F.; Campos, M.; Beltrán, G.; Gaforio, J.J. Bioactive properties of the main triterpenes found in olives, virgin olive oil, and leaves of Olea europaea. J. Agric. Food Chem. 2013, 61, 12173–12182. [Google Scholar] [CrossRef] [PubMed]
  145. Khiev, P.; Cai, X.F.; Chin, Y.W.; Ahn, K.S.; Lee, H.K.; Oh, S.R. Cytotoxic terpenoids from the methanolic extract of Bridelia cambodiana. J. Korean Soc. Appl. Biol. Chem. 2009, 52, 626–631. [Google Scholar] [CrossRef]
  146. Babalola, I.T.; Shode, F.O. Ubiquitous ursolic acid: A potential pentacyclic triterpene natural product. J. Pharmacogn. Phytochem. 2013, 2, 214–222. [Google Scholar]
  147. Chen, H.; Gao, Y.; Wang, A.; Zhou, X.; Zheng, Y.; Zhou, J. Evolution in medicinal chemistry of ursolic acid derivatives as anticancer agents. Eur. J. Med. Chem. 2015, 92, 648–655. [Google Scholar] [CrossRef] [PubMed]
  148. Shanmugam, M.K.; Dai, X.; Kumar, A.P.; Tan, B.K.; Sethi, G.; Bishayee, A. Ursolic acid in cancer prevention and treatment: Molecular targets, pharmacokinetics and clinical studies. Biochem. Pharmacol. 2013, 85, 1579–1587. [Google Scholar] [CrossRef] [PubMed]
  149. Wei, H.Y.; Yang, M.L. Mechanistic Perspectives of Maslinic Acid in Targeting Inflammation. Biochem. Res. Int. 2015, 279356. [Google Scholar] [CrossRef]
  150. Lee, J.H.; Lee, J.Y.; Park, J.H.; Jung, H.S.; Kim, J.S.; Kang, S.S.; Kim, Y.S.; Han, Y. Immunoregulatory activity by daucosterol, a β-sitosterol glycoside, induces protective Th1 immune response against disseminated Candidiasis in mice. Vaccine 2007, 25, 3834–3840. [Google Scholar] [CrossRef] [PubMed]
  151. Chen, L.S.; Zheng, D.S. Bioactive constituents from the rhizomes of Aster tataricus L. f. afford the treatment of asthma through activation of β2AR and inhibition of NF-κB. Lat. Am. J. Pharm. 2015, 34, 291–295. [Google Scholar]
  152. Huang, L.J.; Gao, W.Y.; Li, X.; Zhao, W.S.; Huang, L.Q.; Liu, C.X. Evaluation of the In Vivo Anti-inflammatory Effects of Extracts from Pyrus bretschneideri Rehd. J. Agric. Food Chem. 2010, 58, 8983–8987. [Google Scholar] [CrossRef] [PubMed]
  153. Mavar-Manga, H.; Haddad, M.; Pieters, L.; Baccelli, C.; Penge, A.; Quetin-Leclercq, J. Anti-inflammatory compounds from leaves and root bark of Alchornea cordifolia (Schumach. & Thonn.) Muell. Arg. J. Ethnopharmacol. 2008, 115, 25–29. [Google Scholar] [PubMed]
  154. Kim, J.S.; Kim, J.C.; Shim, S.H.; Lee, E.J.; Jin, W.; Bae, K.; Son, K.H.; Kim, H.P.; Kang, S.S.; Chang, H.W. Chemical constituents of the root of Dystaenia takeshimana and their anti-inflammatory activity. Arch. Pharmacal. Res. 2006, 29, 617–623. [Google Scholar] [CrossRef]
  155. Luo, W.; Zhao, M.; Yang, B.; Shen, G.; Rao, G. Identification of bioactive compounds in Phyllenthus emblica L. fruit and their free radical scavenging activities. Food Chem. 2009, 114, 499–504. [Google Scholar] [CrossRef]
  156. Guo, X.D.; Wang, M.; Gao, J.M.; Shi, X.W. Bioguided fraction of antioxidant activity of ethanol extract from tartary buckwheat bran. Cereal Chem. 2012, 89, 311–315. [Google Scholar] [CrossRef]
  157. Qing, Z.J.; Wang, Y.; Hui, L.Y.; Yong, L.W.; Long, L.H.; Ao, D.J.; Xia, P.L. Two new natural products from the fruits of Alpinia oxyphylla with inhibitory effects on nitric oxide production in lipopolysaccharide-activated RAW264.7 macrophage cells. Arch. Pharmacal. Res. 2012, 35, 2143–2146. [Google Scholar] [CrossRef] [PubMed]
  158. Kamurthy, H.; Sumalatha, C.; Rao, N.; Sudhakar, M. Antinocieptive activity of stigmosterol-3-glyceryl-2′-linoleiate, campesterol and daucosterol isolated from Aerva lanata Linn. aerial parts. Asian J. Pharm. Clin. Res. 2013, 6, 149–152. [Google Scholar]
  159. Han, X.N.; Liu, C.Y.; Liu, Y.L.; Xu, Q.M.; Li, X.R.; Yang, S.L. New Triterpenoids and Other Constituents from the Fruits of Benincasa hispida (Thunb.) Cogn. J. Agric. Food Chem. 2013, 61, 12692–12699. [Google Scholar] [CrossRef] [PubMed]
  160. Chung, M.J.; Lee, S.; Park, Y.I.; Lee, J.; Kwon, K.H. Neuroprotective effects of phytosterols and flavonoids from Cirsium setidens and Aster scaber in human brain neuroblastoma SK-N-SH cells. Life Sci. 2016, 148, 173–182. [Google Scholar] [CrossRef] [PubMed]
  161. Jiang, L.H.; Yuan, X.L.; Yang, N.Y.; Ren, L.; Zhao, F.M.; Luo, B.X.; Bian, Y.Y.; Xu, J.Y.; Lu, D.X.; Zheng, Y.Y.; et al. Daucosterol protects neurons against oxygen-glucose deprivation/reperfusion-mediated injury by activating IGF1 signaling pathway. J. Steroid Biochem. Mol. Biol. 2015, 152, 45–52. [Google Scholar] [CrossRef] [PubMed]
  162. Jiang, L.H.; Yang, N.Y.; Yuan, X.L.; Zou, Y.J.; Zhao, F.M.; Chen, J.P.; Wang, M.Y.; Lu, D.X. Daucosterol promotes the proliferation of neural stem cells. J. Steroid Biochem. Mol. Biol. 2014, 140, 90–99. [Google Scholar] [CrossRef] [PubMed]
  163. Bahadori, M.B.; Dinparast, L.; Valizadeh, H.; Farimani, M.M.; Ebrahimi, S.N. Bioactive constituents from roots of Salvia syriaca L.: Acetylcholinesterase inhibitory activity and molecular docking studies. S. Afr. J. Bot. 2016, 106, 1–4. [Google Scholar] [CrossRef]
  164. Zhao, C.; She, T.; Wang, L.; Su, Y.; Qu, L.; Gao, Y.; Xu, S.; Cai, S.; Shou, C. Daucosterol inhibits cancer cell proliferation by inducing autophagy through reactive oxygen species-dependent manner. Life Sci. 2015, 137, 37–43. [Google Scholar] [CrossRef] [PubMed]
  165. Esmaeili, M.A.; Farimani, M.M. Inactivation of PI3K/Akt pathway and upregulation of PTEN gene are involved in daucosterol, isolated from Salvia sahendica, induced apoptosis in human breast adenocarcinoma cells. S. Afr. J. Bot. 2014, 93, 37–47. [Google Scholar] [CrossRef]
  166. Manayi, A.; Saeidnia, S.; Ostad, S.N.; Hadjiakhoondi, A.; Ardekani, M.R.; Vazirian, M.; Akhtar, Y.; Khanavi, M. Chemical constituents and cytotoxic effect of the main compounds of Lythrum salicaria L. Z. Naturforsch. C J. Biosci. 2013, 68, 367–375. [Google Scholar] [CrossRef]
  167. Salimi, M.; Ardestaniyan, M.H.; Mostafapour, K.H.; Saeidnia, S.; Gohari, A.R.; Amanzadeh, A.; Sanati, H.; Sepahdar, Z.; Ghorbani, S.; Salimi, M. Anti-proliferative and apoptotic activities of constituents of chloroform extract of Juglans regia leaves. Cell. Prolif. 2014, 47, 172–179. [Google Scholar] [CrossRef] [PubMed]
  168. Zeng, X.; Li, C.Y.; Wang, H.; Qiu, Q.; Qiu, G.; He, X. Unusual lipids and acylglucosylsterols from the roots of Livistona chinensis. Phytochem. Lett. 2013, 6, 36–40. [Google Scholar] [CrossRef]
  169. Lee, D.Y.; Lee, S.J.; Kwak, H.Y.; Jung, L.; Heo, J.; Hong, S.; Kim, G.W.; Baek, N.I. Sterols isolated from Nuruk (Rhizopus oryzae KSD-815) inhibit the migration of cancer cells. J. Microbiol. Biotechnol. 2009, 19, 1328–1332. [Google Scholar] [CrossRef] [PubMed]
  170. Gao, D.; Zhang, Y.L.; Xu, P.; Lin, Y.X.; Yang, F.Q.; Liu, J.H.; Zhu, H.W.; Xia, Z.N. In vitro evaluation of dual agonists for PPARγ/β from the flower of Edgeworthia gardneri (wall.) Meisn. J. Ethnopharmacol. 2015, 162, 14–19. [Google Scholar] [CrossRef] [PubMed]
  171. Sheng, Z.; Dai, H.; Pan, S.; Wang, H.; Hu, Y.; Ma, W. Isolation and characterization of an α-glucosidase inhibitor from Musa spp. (Baxijiao) flowers. Molecules 2014, 19, 10563–10573. [Google Scholar] [CrossRef] [PubMed]
  172. Chen, W.H.; Liu, W.J.; Wang, Y.; Song, X.P.; Chen, G.Y. A new naphthoquinone and other antibacterial constituents from the roots of Xanthium sibiricum. Nat. Prod. Res. 2015, 29, 739–744. [Google Scholar] [CrossRef] [PubMed]
  173. Lee, D.G.; Lee, A.Y.; Kim, S.J.; Lee, S. Antibacterial phytosterols and alkaloids from Lycoris radiata. Nat. Prod. Sci. 2014, 20, 107–112. [Google Scholar]
  174. Cho, E.J.; Choi, J.Y.; Lee, K.H.; Lee, S. Isolation of antibacterial compounds from Parasenecio pseudotaimingasa. Hort. Environ. Biotechnol. 2012, 53, 561–564. [Google Scholar] [CrossRef]
  175. Sultana, N.; Afolayan, A.J. A novel daucosterol derivative and antibacterial activity of compounds from Arctotis arctotoides. Nat. Prod. Res. 2007, 21, 889–896. [Google Scholar] [CrossRef] [PubMed]
  176. Kimura, T.; Jyo, M.; Nakamura, N.; Komatsu, K.; Hattori, M.; Shimotohno, K.; Shimotohno, K.; Kakiuchi, N. Inhibitory effect of Tibetan medicinal plants on viral polymerases. J. Trad. Med. 2003, 20, 243–250. [Google Scholar]
  177. Jeong, J.S.; Lee, J.-H.; Lee, S.H.; Jeong, C.S. Suppressive actions of Astragali Radix (AR) ethanol extract and isolated astragaloside I on HCl/ethanol-induced gastric lesions. Biomol. Ther. 2009, 17, 62–69. [Google Scholar] [CrossRef]
  178. Yan, X.T.; Lee, S.-H.; Li, W.; Jang, H.D.; Kim, Y.H. Terpenes and sterols from the fruits of Prunus mume and their inhibitory effects on osteoclast differentiation by suppressing tartrate-resistant acid phosphatase activity. Arch. Pharmacal. Res. 2015, 38, 186–192. [Google Scholar] [CrossRef] [PubMed]
  179. Darbandi, T.; Honarvar, B.; Sinaei Nobandegani, M.; Rezaei, A. Extraction of Ziziphora tenuior essential oil using supercritical CO2. Eur. J. Exp. Biol. 2013, 3, 687–695. [Google Scholar]
  180. Barra, A. Factors affecting chemical variability of essential oils: A review of recent developments. Nat. Prod. Commun. 2009, 4, 1147–1154. [Google Scholar] [PubMed]
  181. Figueiredo, C.A.; Barroso, J.G.; Pedro, L.G.; Scheffer, J.J.C. Factors affecting secondary metabolite production in plants: Volatile components and essential oils. Flavour Frag. J. 2008, 23, 213–226. [Google Scholar] [CrossRef]
  182. Amiri, H. Influence of growth phase on the essential oil composition of Ziziphora clinopodioides Lam. Nat. Prod. Res. 2009, 23, 601–606. [Google Scholar] [CrossRef] [PubMed]
  183. Goldansaz, S.M.; Rezaee, M.B.; Jaimand, K.; Mirhoseini, A. Study of essential oils compositions of three species of medicinal plants from ShirKooh mountain (Up village) on Yazd province. J. Med. Plants By-Prod. 2014, 3, 187–191. [Google Scholar]
  184. Aghajani, Z.; Assadian, F.; Masoudi, S.; Chalabian, F.; Esmaeili, A.; Tabatabaei-Anaraki, M.; Rustaiyan, A. Chemical composition and In Vitro Antibacterial Activities of The Oil Ziziphora clinopodioides and Z. capitata subsp. capitata from Iran. Chem. Nat. Compd. 2008, 44, 387–389. [Google Scholar] [CrossRef]
  185. Kasumov, F.Y.; Kyazimov, I.M.; Dembitskii, A.D.; Ismailov, N.M. Component composition of the essential oils of Ziziphora species. Chem. Nat. Compd. 1988, 23, 636–637. [Google Scholar] [CrossRef]
  186. Dembitskii, A.D.; Bergaliev, E.S.; Kyazimov, M.I. Chemical composition of the essential oils of Ziziphora growing under various ecological conditions. Chem. Nat. Compd. 1994, 30, 673–675. [Google Scholar] [CrossRef]
  187. Nagawa, C.B.; Boehmdorfer, S.; Rosenau, T. Chemical composition of volatiles extracted from indigenous tree species of Uganda: composition of bark extracts from Psorospermum febrifugum and Milicia excelsa. Holzforschung 2015, 69, 815–821. [Google Scholar] [CrossRef]
  188. Singh, H.P.; Kaur, S.; Mittal, S.; Batish, D.R.; Kohli, R.K. In vitro screening of essential oil from young and mature leaves of Artemisia scoparia compared to its major constituents for free radical scavenging activity. Food Chem. Toxicol. 2010, 48, 1040–1044. [Google Scholar] [CrossRef] [PubMed]
  189. Fogang, H.P.D.; Tapondjou, L.A.; Womeni, H.M.; Quassinti, L.; Bramucci, M.; Vitali, L.A.; Petrelli, D.; Lupidi, G.; Maggi, F.; Papa, F.; et al. Characterization and biological activity of essential oils from fruits of Zanthoxylum xanthoxyloides Lam. and Z. leprieurii Guill. & Perr., two culinary plants from Cameroon. Flavour Fragr. J. 2012, 27, 171–179. [Google Scholar]
  190. Abdelgaleil, S.A.M.; Mohamed, M.I.E.; Badawy, M.E.I.; El-arami, S.A. Fumigant and Contact Toxicities of Monoterpenes to Sitophilus oryzae (L.) and Tribolium castaneum (Herbst) and their Inhibitory Effects on Acetylcholinesterase Activity. J. Chem. Ecol. 2009, 35, 518–525. [Google Scholar] [CrossRef] [PubMed]
  191. Liu, Z.L.; Du, S.S. Fumigant components from the essential oil of Evodia rutaecarpa Hort unripe fruits. Eur. J. Chem. 2011, 8, 1937–1943. [Google Scholar]
  192. do Vale, T.G.; Furtado, E.C.; Santos, J.G., Jr.; Viana, G.S.B. Central effects of citral, myrcene and limonene, constituents of essential oil chemotypes from Lippia alba (Mill.) N.E. Brown. Phytomedicine 2002, 9, 709–714. [Google Scholar] [CrossRef] [PubMed]
  193. Souza, M.C.; Siani, A.C.; Ramos, M.F.S.; Menezes-de-Lima, O.J.; Henriques, M.G. Evaluation of anti-inflammatory activity of essential oils from two Asteraceae species. Pharmazie 2003, 58, 582–586. [Google Scholar] [PubMed]
  194. Mitic-Culafic, D.; Zegura, B.; Nikolic, B.; Vukovic-Gacic, B.; Knezevic-Vukcevic, J.; Filipic, M. Protective effect of linalool, myrcene and eucalyptol against t-butyl hydroperoxide induced genotoxicity in bacteria and cultured human cells. Food Chem. Toxicol. 2009, 47, 260–266. [Google Scholar] [CrossRef] [PubMed]
  195. Ciftci, O.; Tanyildizi, S.; Godekmerdan, A. Curcumin, myrcen and cineol modulate the percentage of lymphocyte subsets altered by 2,3,7,8-tetrachlorodibenzo-p-dioxins (TCDD) in rats. Hum. Exp. Toxicol. 2011, 30, 1986–1994. [Google Scholar] [CrossRef] [PubMed]
  196. Ciftci, O.; Ozdemir, I.; Tanyildizi, S.; Yildiz, S.; Oguzturk, H. Antioxidative effects of curcumin, β-myrcene and 1,8-cineole against 2,3,7,8-tetrachlorodibenzo-p-dioxin induced oxidative stress in rats liver. Toxicol. Ind. Health. 2011, 27, 447–453. [Google Scholar] [CrossRef] [PubMed]
  197. Ciftci, O.; Oztanir, M.N.; Cetin, A. Neuroprotective Effects of β-Myrcene Following Global Cerebral Ischemia/Reperfusion-Mediated Oxidative and Neuronal Damage in a C57BL/J6 Mouse. Neurochem. Res. 2014, 39, 1717–1723. [Google Scholar] [CrossRef] [PubMed]
  198. Bonamin, F.; Moraes, T.M.; dos Santos, R.C.; Kushima, H.; Faria, F.M.; Silva, M.A.; Junior, I.V.; Nogueira, L.; Bauab, T.M.; Souza Brito, A.R.M.; et al. The effect of a minor constituent of essential oil from Citrus aurantium: The role of β-myrcene in preventing peptic ulcer disease. Chem.-Biol. Interact. 2014, 212, 11–19. [Google Scholar] [CrossRef] [PubMed]
  199. Guimarães, A.G.; Quintans, J.S.; Quintans-Júnior, L.J. Monoterpenes with analgesic activity—A systematic review. Phytother. Res. 2013, 27, 1–15. [Google Scholar] [CrossRef] [PubMed]
  200. Jaeger, W. Metabolism of terpenoids in animal models and humans. In Handbook of Essential Oils; Baser, K.H.C., Buchbauer, G., Eds.; CRC Press: Boca Raton, FL, USA, 2010. [Google Scholar]
  201. Sonboli, A.; Mirjalili, M.H.; Hadian, J.; Ebrahimi, S.N.; Yousefzadi, M. Antibacterial Activity and Composition of the Essential Oil of Ziziphora clinopodioides subsp. bungeana (Juz.) Rech.f. from Iran. Z. Naturforsch. C. 2006, 61, 677–680. [Google Scholar] [CrossRef] [PubMed]
  202. Karimi, I.; Hayatgheybi, H.; Motamedi, S.; Naseri, D.; Shamspur, T.; Afzali, D.; Aghdam, A.H. Chemical Composition and Hypolipidemic Effects of an Aromatic Water of Ziziphora tenuior L. in Cholesterol-fed Rabbits. J. Appl. Biol. Sci. 2013, 7, 61–67. [Google Scholar]
  203. Valente, J.; Zuzarte, M.; Goncalves, M.J.; Lopes, M.C.; Cavaleiro, C.; Salgueiro, L.; Cruz, M.T. Antifungal, antioxidant and anti-inflammatory activities of Oenanthe crocata L. essential oil. Food Chem. Toxicol. 2013, 62, 349–354. [Google Scholar] [CrossRef] [PubMed]
  204. Cavaleiro, C.; Salgueiro, L.; Goncalves, M.J.; Hrimpeng, K.; Pinto, J.; Pinto, E. Antifungal activity of the essential oil of Angelica major against Candida, Cryptococcus, Aspergillus and dermatophyte species. J. Nat. Med. 2015, 69, 241–248. [Google Scholar] [CrossRef] [PubMed]
  205. Perumalsamy, H.; Kim, N.J.; Ahn, Y.J. Larvicidal activity of compounds isolated from Asarum heterotropoides against Culex pipiens pallens, Aedes aegypti, and Ochlerotatus togoi (Diptera: Culicidae). J. Med. Entomol. 2009, 46, 1420–1423. [Google Scholar] [CrossRef] [PubMed]
  206. Cheng, S.S.; Huang, C.G.; Chen, Y.J.; Yu, J.J.; Chen, W.J.; Chang, S.T. Chemical compositions and larvicidal activities of leaf essential oils from two Eucalyptus species. Bioresour. Technol. 2009, 100, 452–456. [Google Scholar] [CrossRef] [PubMed]
  207. Lima, D.F.; Brandao, M.S.; Moura, J.B.; Leitão, J.M.; Carvalho, F.A.; Miúra, L.M.; Leite, J.R.; Sousa, D.P.; Almeida, F.R. Antinociceptive activity of the monoterpene α-phellandrene in rodents: Possible mechanisms of action. J. Pharm. Pharmacol. 2012, 64, 283–292. [Google Scholar] [CrossRef] [PubMed]
  208. Piccinelli, A.C.; Santos, J.A.; Konkiewitz, E.C.; Oesterreich, S.A.; Formagio, A.S.; Croda, J.; Ziff, E.B.; Kassuya, C.A. Antihyperalgesic and antidepressive actions of (R)-(+)-limonene, α-phellandrene, and essential oil from Schinus terebinthifolius fruits in a neuropathic pain model. Nutr. Neurosci. 2015, 18, 217–224. [Google Scholar] [CrossRef] [PubMed]
  209. Hsieh, L.C.; Hsieh, S.L.; Chen, C.T.; Chung, J.G.; Wang, J.J.; Wu, C.C. Induction of α-Phellandrene on Autophagy in Human Liver Tumor Cells. Am. J. Chin. Med. 2015, 43, 121–136. [Google Scholar] [CrossRef] [PubMed]
  210. Hsieh, S.L.; Li, Y.C.; Chang, W.C.; Chung, J.G.; Hsieh, L.C.; Wu, C.C. Induction of Necrosis in Human Liver Tumor Cells by α-Phellandrene. Nutr. Cancer 2014, 66, 970–979. [Google Scholar] [CrossRef] [PubMed]
  211. Lin, J.J.; Hsu, S.C.; Lu, K.W.; Ma, Y.S.; Wu, C.C.; Lu, H.F.; Chen, J.C.; Lin, J.G.; Wu, P.P.; Chung, J.G. α-Phellandrene-induced apoptosis in mice leukemia WEHI-3 cells in vitro. Environ. Toxicol. 2015. [Google Scholar] [CrossRef] [PubMed]
  212. Lin, J.J.; Lin, J.H.; Hsu, S.C.; Weng, S.W.; Huang, Y.P.; Tang, N.Y.; Lin, J.G.; Chung, J.G. α-Phellandrene promotes immune responses in normal mice through enhancing macrophage phagocytosis and natural killer cell activities. In Vivo 2013, 27, 809–814. [Google Scholar] [PubMed]
  213. Yoshida, N.; Koizumi, M.; Adachi, I.; Kawakami, J. Inhibition of P-glycoprotein-mediated transport by terpenoids contained in herbal medicines and natural products. Food Chem. Toxicol. 2006, 44, 2033–2039. [Google Scholar] [CrossRef] [PubMed]
  214. Ito, K.; Ito, M. Sedative effects of vapor inhalation of the essential oil of Microtoena patchoulii and its related compounds. J. Nat. Med. 2011, 65, 336–343. [Google Scholar] [CrossRef] [PubMed]
  215. Ito, K.; Ito, M. The sedative effect of inhaled terpinolene in mice and its structure-activity relationships. J. Nat. Med. 2013, 67, 833–837. [Google Scholar] [CrossRef] [PubMed]
  216. Pongprayoon, U.; Soontornsaratune, P.; Jarikasem, S.; Sematong, T.; Wasuwat, S.; Claeson, P. Topical antiinflammatory activity of the major lipophilic constituents of the rhizome of Zingiber cassumunar. Part 1. The essential oil. Phytomedicine 1997, 3, 319–322. [Google Scholar] [CrossRef]
  217. Ruberto, G.; Baratta, M.T. Antioxidant activity of selected essential oil components in two lipid model systems. Food Chem. 2000, 69, 167–174. [Google Scholar] [CrossRef]
  218. Kim, H.J.; Chen, F.; Wu, C.; Wang, X.; Chung, H.Y.; Jin, Z. Evaluation of Antioxidant Activity of Australian Tea Tree (Melaleuca alternifolia) Oil and Its Components. J. Agric. Food Chem. 2004, 52, 2849–2854. [Google Scholar] [CrossRef] [PubMed]
  219. Adegoke, G.O.; Iwahashi, H.; Komatsu, Y.; Obuchi, K.; Iwahashi, Y. Inhibition of food spoilage yeasts and aflatoxigenic moulds by monoterpenes of the spice Aframomum danielli. Flavour Fragr. J. 2000, 15, 147–150. [Google Scholar] [CrossRef]
  220. Astani, A.; Reichling, J.; Schnitzler, P. Comparative study on the antiviral activity of selected monoterpenes derived from essential oils. Phytother. Res. 2010, 24, 673–679. [Google Scholar] [CrossRef] [PubMed]
  221. Santos, M.R.V.; Moreira, F.V.; Fraga, B.P.; de Souza, D.P.; Bonjardim, L.R.; Quintans-Júnior, L.J. Cardiovascular effects of monoterpenes: A review. Rev. Bras. Farmacogn. 2011, 21, 764–771. [Google Scholar] [CrossRef]
  222. Baldissera, M.D.; Grando, T.H.; Souza, C.F.; Gressler, L.T.; Stefani, L.M.; da Silva, A.S.; Monteiro, S.G. In vitro and in vivo action of terpinen‑4‑ol, γ‑terpinene, and α‑terpinene against Trypanosoma evansi. Exp. Parasitol. 2016, 162, 43–48. [Google Scholar] [CrossRef] [PubMed]
  223. Bourgou, S.; Pichette, A.; Marzouk, B.; Legault, J. Bioactivities of black cumin essential oil and its main terpenes from Tunisia. S. Afr. J. Bot. 2010, 76, 210–216. [Google Scholar] [CrossRef]
  224. Bonesi, M.; Menichini, F.; Tundis, R.; Loizzo, M.R.; Conforti, F.; Passalacqua, N.G.; Statti, G.A.; Menichini, N.G. Acetylcholinesterase and butyrylcholinesterase inhibitory activity of Pinus species essential oils and their constituents. J. Enzym. Inhib. Med. Chem. 2010, 25, 622–628. [Google Scholar] [CrossRef] [PubMed]
  225. Satou, T.; Miyahara, N.; Murakami, S.; Hayashi, S.; Koike, K. Differences in the effects of essential oil from Citrus junos and (+)-limonene on emotional behavior in mice. J. Essent. Oil Res. 2012, 24, 493–500. [Google Scholar] [CrossRef]
  226. Aydin, E.; Turkez, H.; Tasdemir, S. Anticancer and antioxidant properties of terpinolene in rat brain cells. Arhiv za Higijenu Rada i Toksikologiju 2013, 64, 415–424. [Google Scholar] [PubMed]
  227. Okumura, N.; Yoshida, H.; Nishimura, Y.; Kitagishi, Y.; Matsuda, S. Terpinolene, a component of herbal sage, downregulates AKT1 expression in K562 cells. Oncol. Lett. 2012, 3, 321–324. [Google Scholar] [PubMed]
  228. Park, I.K.; Lee, S.G.; Choi, D.H.; Park, J.D.; Ahn, Y.J. Insecticidal activities of constituents identified in the essential oil from leaves of Chamaecyparis obtusa against Callosobruchus chinensis (L.) and Sitophilus oryzae (L.). J. Stored Prod. Res. 2003, 39, 375–384. [Google Scholar] [CrossRef]
  229. Cheng, S.S.; Chang, H.T.; Lin, C.Y.; Chen, P.S.; Huang, C.G.; Chen, W.J.; Chang, S.T. Insecticidal activities of leaf and twig essential oils from Clausena excavata against Aedes aegypti and Aedes albopictus larvae. Pest Manag. Sci. 2009, 65, 339–343. [Google Scholar] [CrossRef] [PubMed]
  230. Graßmann, J.; Hippeli, S.; Spitzenberger, R.; Elstner, E.F. The monoterpene terpinolene from the oil of Pinus mugo L. in concert with α-tocopherol and β-carotene effectively prevents oxidation of LDL. Phytomedicine 2005, 12, 416–423. [Google Scholar] [CrossRef] [PubMed]
  231. Garozzo, A.; Timpanaro, R.; Bisignano, B.; Furneri, P.M.; Bisignano, G.; Castro, A. In vitro antiviral activity of Melaleuca alternifolia essential oil. Lett. Appl. Microbiol. 2009, 49, 806–808. [Google Scholar] [CrossRef] [PubMed]
  232. Pirbalouti, A.G.; Amirkhosravi, A.; Bordbar, F. Diversity in the chemical composition of essential oils of Ziziphora tenuior as a potential source of pulegone. Chemija 2013, 24, 234–239. [Google Scholar]
  233. Vogt, J.T.; Shelton, T.G.; Merchant, M.E.; Russel, S.A.; Tanley, M.J.; Appel, A.G. Efficacy of the three citrus oil formulations against Solenopsis invicta Buren (Hymenoptera: Formicidae), the red imported fire ant. J. Agric. Urban Entomol. 2002, 19, 159–171. [Google Scholar]
  234. Lee, S.; Peterson, C.J.; Coats, J.R. Fumigation toxicity of monoterpenoids to several stored product insects. J. Stored Prod. Res. 2003, 39, 77–85. [Google Scholar] [CrossRef]
  235. Rozza, A.L.; Moraes, T.M.; Kushima, H.; Tanimoto, A.; Marques, M.O.; Bauab, T.M.; Hiruma-Lima, C.A.; Pellizzon, C.H. Gastroprotective mechanisms of Citrus lemon (Rutaceae) essential oil and its majority compounds limonene and β-pinene: Involvement of heat-shock protein-70, vasoactive intestinal peptide, glutathione, sulfhydryl compounds, nitric oxide and prostaglandin E2. Chem.-Biol. Interact. 2011, 189, 82–89. [Google Scholar] [CrossRef] [PubMed]
  236. Erasto, P.; Viljoen, A.M. Limonene—A review: Biosynthetic, ecological and pharmacological relevance. Nat. Prod. Commun. 2008, 3, 1193–1202. [Google Scholar]
  237. Maróstica, M.R., Jr.; Pastore, G.M. Limonene and Its Oxyfunctionalized Compounds—Biotransformation by Microorganisms and Their Role as Functional Bioactive Compounds. Food Sci. Biotechnol. 2009, 18, 833–841. [Google Scholar]
  238. Sharopov, F.S.; Setzer, W.N. Chemical diversity of Ziziphora clinopodioides: Composition of the essential oil of Z. clinopodioides from Tajikistan. Nat. Prod. Commun. 2011, 6, 695–698. [Google Scholar] [PubMed]
  239. Samber, N.; Khan, A.; Varma, A.; Manzoor, N. Synergistic anti-candidal activity and mode of action of Mentha piperita essential oil and its major components. Pharm. Biol. 2015, 53, 1496–1504. [Google Scholar] [CrossRef] [PubMed]
  240. Jirovetz, L.; Buchbauer, G.; Bail, S.; Denkova, Z.; Slavchev, A.; Stoyanova, A.; Schmidt, E.; Geissler, M. Antimicrobial activities of essential oils of mint and peppermint as well as some of their main compounds. J. Essent. Oil Res. 2009, 21, 363–366. [Google Scholar] [CrossRef]
  241. Hussain, A.I.; Anwar, F.; Nigam, P.S.; Ashraf, M.; Gilani, A.H. Seasonal variation in content, chemical composition and antimicrobial and cytotoxic activities of essential oils from four Mentha species. J. Sci. Food Agric. 2010, 90, 1827–1836. [Google Scholar] [CrossRef] [PubMed]
  242. Kumar, P.; Mishra, S.; Malik, A.; Satya, S. Insecticidal properties of Mentha species: A review. Ind. Crops Prod. 2011, 34, 802–817. [Google Scholar] [CrossRef]
  243. Herrera, J.M.; Zunino, M.P.; Dambolena, J.S.; Pizzolitto, R.P.; Ganan, N.A.; Lucini, E.I.; Zygadlo, J.A. Terpene ketones as natural insecticides against Sitophilus zeamais. Ind. Crop Prod. 2015, 70, 435–442. [Google Scholar] [CrossRef]
  244. Xue, J.; Li, H.; Deng, X.; Ma, Z.; Fu, Q.; Ma, S. l-Menthone confers antidepressant-like effects in an unpredictable chronic mild stress mouse model via NLRP3 inflammasome-mediated inflammatory cytokines and central neurotransmitters. Pharmacol. Biochem. Behav. 2015, 134, 42–48. [Google Scholar] [CrossRef] [PubMed]
  245. Bowers, W.S.; Ortego, F.; You, X.; Evans, P.H. Insect repellents from the Chinese prickly ash Zanthoxylum bungeanum. J. Nat. Prod. 1993, 56, 935–938. [Google Scholar] [CrossRef]
  246. Abdelgaleil, S.A.M.; Abbassy, M.A.; Belal, A.S.H.; Rasoul, M.A.A. Bioactivity of two major constituents isolated from the essential oil of Artemisia judaica L. Bioresour. Technol. 2008, 99, 5947–5950. [Google Scholar] [CrossRef] [PubMed]
  247. Ketoh, G.K.; Koumaglo, H.K.; Glitho, I.A.; Huignard, J. Comparative effects of Cymbopogon schoenanthus essential oil and piperitone on Callosobruchus maculatus development. Fitoterapia 2006, 77, 506–510. [Google Scholar] [CrossRef] [PubMed]
  248. Shahverdi, A.R.; Rafii, F.; Tavassoli, F.; Bagheri, M.; Attar, F.; Ghahraman, A. Piperitone from Mentha longifolia var. chorodictya Rech F. reduces the nitrofurantoin resistance of strains of Enterobacteriaceae. Phytother. Res. 2004, 18, 911–914. [Google Scholar] [CrossRef] [PubMed]
  249. Shahverdi, A.R.; Mirzaie, S.; Rafii, F.; Kakavand, M.; Foroumadi, A. Monoterpenes as nitrofurantoin resistance modulating agents: Minimal structural requirements, molecular dynamics simulations, and the effect of piperitone on the emergence of nitrofurantoin resistance in Enterobacteriaceae. J. Mol. Model. 2015, 21, 198. [Google Scholar] [CrossRef] [PubMed]
  250. Cárdenas-Ortega, N.C.; Zavala-Sanchez, M.A.; Aguirre-Rivera, J.R.; Pérez-González, C.; Pérez-Gutiérrez, S. Chemical Composition and Antifungal Activity of Essential Oil of Chrysactinia mexicana Gray. J Agric. Food Chem. 2005, 53, 4347–4349. [Google Scholar] [CrossRef] [PubMed]
  251. Ozturk, S.; Ercisli, S. The chemical composition of essential oil and in vitro antibacterial activities of essential oil and methanol extract of Ziziphora persica Bunge. J. Ethnopharmacol. 2006, 106, 372–376. [Google Scholar] [CrossRef] [PubMed]
  252. Oumzil, H.; Ghoulami, S.; Rhajaoui, M.; Ilidrissi, A.; Fkih-Tetouani, S.; Faid, M.; Benjouad, A. Antibacterial and antifungal activity of essential oils of Mentha suaveolens. Phytother. Res. 2002, 16, 727–731. [Google Scholar] [CrossRef] [PubMed]
  253. Koliopoulos, G.; Pitarokili, D.; Kioulos, E.; Michaelakis, A.; Tzakou, O. Chemical composition and larvicidal evaluation of Mentha, Salvia, and Melissa essential oils against the West Nile virus mosquito Culex pipiens. Parasitol. Res. 2010, 107, 327–335. [Google Scholar] [CrossRef] [PubMed]
  254. Tripathi, A.K.; Prajapati, V.; Ahmad, A.; Aggarwal, K.K.; Khanuja, S.P. Piperitenone oxide as toxic, repellent, and reproduction retardant toward malarial vector Anopheles stephensi (Diptera: Anophelinae). J. Med. Entomol. 2004, 41, 691–698. [Google Scholar] [CrossRef] [PubMed]
  255. Sousa, P.J.C.; Linard, C.F.; Azevedo-Batista, D.; Oliveira, A.C.; Coelho-de-Souza, A.N.; Leal-Cardoso, J.H. Antinociceptive effects of the essential oil of Mentha x villosa leaf and its major constituent piperitenone oxide in mice. Braz. J. Med. Biol. Res. 2009, 42, 655–659. [Google Scholar] [PubMed]
  256. Civitelli, L.; Panella, S.; Marcocci, M.E.; de Petris, A.; Garzoli, S.; Pepi, F.; Vavala, E.; Ragno, R.; Nencioni, L.; Palamara, A.T.; et al. In vitro inhibition of herpes simplex virus type 1 replication by Mentha suaveolens essential oil and its main component piperitenone oxide. Phytomedicine 2014, 21, 857–865. [Google Scholar] [CrossRef] [PubMed]
  257. Meepagala, K.M.; Kuhajek, J.M.; Sturtz, G.D.; Wedge, D.E. Vulgarone B, the Antifungal Constituent in the Steam-Distilled Fraction of Artemisia douglasiana. J. Chem. Ecol. 2003, 29, 1771–1780. [Google Scholar] [CrossRef] [PubMed]
  258. Papachristos, D.P.; Karamanoli, K.I.; Stamopoulos, D.C.; Menkissoglu-Spiroudi, U. The relationship between the chemical composition of three essential oils and their insecticidal activity against Acanthoscelides obtectus (Say). Pest Manag. Sci. 2004, 60, 514–520. [Google Scholar] [CrossRef] [PubMed]
  259. Sezik, E.; Tümen, G.; Başer, K.H.C. Ziziphora tenuior L. a new source of pulegone. Flav. Fragr. J. 1991, 6, 101–104. [Google Scholar] [CrossRef]
  260. Thodgdon-A, J.; Inprakhon, P. Composition and biological activities of essential oils from Limnophila geoffrayi Bonati. World J. Microbiol. Biotechnol. 2009, 25, 1313–1320. [Google Scholar] [CrossRef]
  261. De Cássia da Silveira e Sá, R.; Andrade, L.N.; de Sousa, D.P. A review on anti-inflammatory activity of monoterpenes. Molecules 2013, 18, 1227–1254. [Google Scholar] [CrossRef] [PubMed]
  262. Fawzy, G.A.; Al Ati, H.Y.; El Gamal, A.A. Chemical composition and biological evaluation of essential oils of Pulicaria jaubertii. Pharmacogn. Mag. 2013, 9, 28–32. [Google Scholar] [CrossRef] [PubMed]
  263. Znini, M.; Cristofari, G.; Majidi, L.; Paolini, J.; Disjobert, J.M.; Costa, J. Essential oil composition and antifungal activity of Pulicaria mauritanica Coss., against postharvest phytopathogenic fungi in apples. LWT Food Sci. Technol. 2013, 54, 564–569. [Google Scholar] [CrossRef]
  264. Han, J.; Kim, S.I.; Choi, B.R.; Lee, S.G.; Ahn, Y.J. Fumigant toxicity of lemon eucalyptus oil constituents to acaricide-susceptible and acaricide-resistant Tetranychus urticae. Pest Manag. Sci. 2011, 67, 1583–1588. [Google Scholar] [CrossRef] [PubMed]
  265. Kamatou, G.P.P.; Vermaak, I.; Viljoen, A.M.; Laqrence, B.M. Menthol: A simple monoterpene with remarkable biological properties. Phytochemistry 2013, 96, 15–25. [Google Scholar] [CrossRef] [PubMed]
  266. Rozza, A.L.; Hiruma-Lima, C.A.; Takahira, R.K.; Padovani, C.R.; Pellizzon, C.H. Effect of menthol in experimentally induced ulcers: Pathways of gastroprotection. Chem.-Biol. Interact. 2013, 206, 272–278. [Google Scholar] [CrossRef] [PubMed]
  267. Rozza, A.L.; Meira de Faria, F.; Souza Brito, A.R.; Pellizon, C.H. The gastroprotective effect of menthol: Involvement of anti-apoptotic, antioxidant and anti-inflammatory activities. PLoS ONE 2014, 9, e86686. [Google Scholar] [CrossRef] [PubMed]
  268. Ton, H.T.; Smart, A.E.; Aguilar, B.L.; Olson, T.T.; Kellar, K.J.; Ahern, G.P. Menthol enhances the desensitization of human α3β4 nicotinic acetylcholine receptors. Mol. Pharmacol. 2015, 88, 256–264. [Google Scholar] [CrossRef] [PubMed]
  269. Orhan, I.; Kartal, M.; Kan, Y.; Sener, B. Activity of essential oils and individual components against acetyl- and butyrylcholinesterase. Z. Naturforsch. C J. Biosci. 2008, 63, 547–553. [Google Scholar]
  270. Osawa, K.; Saeki, T.; Yasuda, H.; Hamashima, H.; Sasatsu, M.; Arai, T. The antibacterial activities of peppermint oil and green tea polyphenols, alone and in combination, against enterohemorrhagic Escherichia coli. Biocontrol. Sci. 1999, 4. [Google Scholar] [CrossRef]
  271. Park, J.H.; Yang, J.Y.; Lee, H.S. Acaricidal activity of constituents derived from peppermint oil against Tyrophagus putrescentiae. J. Food Protect. 2014, 77, 1819–1823. [Google Scholar] [CrossRef] [PubMed]
  272. De Sousa, D.P.; Raphael, E.; Brocksom, U.; Brocksom, T.J. Sedative effect of monoterpene alcohols in mice: A preliminary screening. Z. Naturforsch. C J. Biosci. 2007, 62, 563–566. [Google Scholar] [CrossRef]
  273. Giweli, A.A.; Dzamic, A.M.; Sokovic, M.D.; Ristic, M.S.; Marin., P.D. Chemical composition, antioxidant and antimicrobial activities of essential oil of Thymus algeriensis wild-growing in Libya. Cent. Eur. J. Biol. 2013, 8, 504–511. [Google Scholar] [CrossRef]
  274. Ho, C.L.; Su, Y.C. Composition, antioxidant and antimicrobial activities of the leaf essential oil of Machilus japonica from Taiwan. Nat. Prod. Commun. 2012, 7, 109–112. [Google Scholar] [PubMed]
  275. Bouchra, C.; Achouri, M.; Hassani, L.M.I.; Hmamouchi, M. Chemical composition and antifungal activity of essential oils of seven Moroccan Labiatae against Botrytis cinerea Pers: Fr. J. Ethnopharmacol. 2003, 89, 165–169. [Google Scholar] [CrossRef]
  276. Kurdelas, R.R.; Lopez, S.; Lima, B.; Feresin, G.E.; Zygadlo, J.; Zacchino, S.; López, M.L.; Tapia, A.; Freile, M.L. Chemical composition, anti-insect and antimicrobial activity of Baccharis darwinii essential oil from Argentina, Patagonia. Ind. Crop Prod. 2012, 40, 261–267. [Google Scholar] [CrossRef]
  277. Zuzarte, M.; Goncalves, M.J.; Cavaleiro, C.; Cruz, M.T.; Benzarti, A.; Marongiu, B.; Maxia, A.; Piras, A.; Salgueiro, L. Antifungal and anti-inflammatory potential of Lavandula stoechas and Thymus herba-barona essential oils. Ind. Crop Prod. 2013, 44, 97–103. [Google Scholar] [CrossRef]
  278. Ahmad, A.; Khan, A.; Manzoor, N. Reversal of efflux-mediated antifungal resistance underlies synergistic activity of two monoterpenes with fluconazole. Eur. J. Pharm. Sci. 2013, 48, 80–86. [Google Scholar] [CrossRef] [PubMed]
  279. Farias-Junior, P.A.; Rios, M.C.; Moura, T.A.; Almeida, R.P.; Alves, P.B.; Blank, A.F.; Fernandes, R.P.M.; Scher, R. Leishmanicidal activity of carvacrol-rich essential oil from Lippia sidoides Cham. Biol. Res. 2012, 45, 399–402. [Google Scholar] [CrossRef] [PubMed]
  280. Mota, M.L.; Lobo, L.T.; Costa, J.M.; Costa, L.S.; Rocha, H.A.; Rocha e Silva, L.F.; Pohlit, A.M.; Neto, V.F. In vitro and in vivo antimalarial activity of essential oils and chemical components from three medicinal plants found in northeastern Brazil. Planta Med. 2012, 78, 658–664. [Google Scholar] [CrossRef] [PubMed]
  281. Ntalli, N.G.; Ferrari, F.; Giannakou, I.; Menkissoglu-Spiroudi, U. Phytochemistry and Nematicidal Activity of the Essential Oils from 8 Greek Lamiaceae Aromatic Plants and 13 Terpene Components. J. Agric. Food Chem. 2010, 58, 7856–7863. [Google Scholar] [CrossRef] [PubMed]
  282. Santoyo, S.; Jaime, L.; Garcia-Risco, M.R.; Ruiz-Rodríguez, A.; Reglero, G. Antiviral Properties of Supercritical CO2 Extracts from Oregano and Sage. Int. J. Food Prop. 2014, 17, 1150–1161. [Google Scholar] [CrossRef]
  283. Melo, J.O.; Fachin, A.L.; Rizo, W.F.; Jesus, H.C.R.; Arrigoni-Blank, M.F.; Alves, P.B.; Marins, M.A.; França, S.C.; Blank, A.F. Cytotoxic effects of essential oils from three Lippia gracilis Schauer genotypes on HeLa, B16, and MCF-7 cells and normal human fibroblasts. Genet. Mol. Res. 2014, 13, 2691–2697. [Google Scholar] [CrossRef] [PubMed]
  284. Jaafari, A.; Mouse, H.A.; Rakib, E.M.; Tilaoui, M.; Benbakhta, C.; Boulli, A.; Abbad, A.; Zyad, A. Chemical composition and antitumor activity of different wild varieties of Moroccan thyme. Rev. Bras. Farmacogn. 2007, 17, 477–491. [Google Scholar] [CrossRef]
  285. Pathania, A.S.; Guru, S.K.; Verma, M.K.; Sharma, C.; Abdullah, S.T.; Malik, F.; Chandra, S.; Katoch, M.; Bhushan, S. Disruption of the PI3K/AKT/mTOR signaling cascade and induction of apoptosis in HL-60 cells by an essential oil from Monarda citriodora. Food Chem. Toxicol. 2013, 62, 246–254. [Google Scholar] [CrossRef] [PubMed]
  286. Deb, D.D.; Parimala, G.; Saravana Devi, S.; Chakraborty, T. Effect of thymol on peripheral blood mononuclear cell PBMC and acute promyelotic cancer cell line HL-60. Chem.-Biol. Interact. 2011, 193, 97–106. [Google Scholar] [CrossRef] [PubMed]
  287. Vicuna, G.C.; Stashenko, E.E.; Fuentes, J.L. Chemical composition of the Lippia origanoides essential oils and their antigenotoxicity against bleomycin-induced DNA damage. Fitoterapia 2010, 81, 343–349. [Google Scholar] [CrossRef] [PubMed]
  288. Riella, K.R.; Marinho, R.R.; Santos, J.S.; Pereira-Filho, R.N.; Cardoso, J.C.; Albuquerque-Junior, R.L.; Thomazzi, S.M. Anti-inflammatory and cicatrizing activities of thymol, a monoterpene of the essential oil from Lippia gracilis, in rodents. J. Ethnopharmacol. 2012, 143, 656–663. [Google Scholar] [CrossRef] [PubMed]
  289. Liang, D.; Li, F.; Fu, Y.; Cao, Y.; Song, X.; Wang, T.; Wang, W.; Guo, M.; Zhou, E.; Li, D.; et al. Thymol Inhibits LPS-Stimulated Inflammatory Response via Down-Regulation of NF-κB and MAPK Signaling Pathways in Mouse Mammary Epithelial Cells. Inflammation 2014, 37, 214–222. [Google Scholar] [CrossRef] [PubMed]
  290. Zhou, E.; Fu, Y.; Wei, Z.; Yu, Y.; Zhang, X.; Yang, Z. Thymol attenuates allergic airway inflammation in ovalbumin (OVA)-induced mouse asthma. Fitoterapia 2014, 96, 131–137. [Google Scholar] [CrossRef] [PubMed]
  291. Wei, Z.; Zhou, E.; Guo, C.; Fu, Y.; Yu, Y.; Li, Y.; Yao, M.; Zhang, N.; Yang, Z. Thymol inhibits Staphylococcus aureus internalization into bovine mammary epithelial cells by inhibiting NF-κB activation. Microb. Pathog. 2014, 71, 15–19. [Google Scholar]
  292. Alavinezhad, A.; Boskabady, M.H. Antiinflammatory, Antioxidant, and Immunological Effects of Carum copticum L. and Some of Its Constituents. Phytother. Res. 2014, 28, 1739–1748. [Google Scholar] [CrossRef] [PubMed]
  293. Archana, P.R.; Rao, B.N.; Ballal, M.; Rao, B.S. Thymol, a naturally occurring monocyclic dietary phenolic compound protects Chinese hamster lung fibroblasts from radiation-induced cytotoxicity. Mutat. Res. Gen. Tox. Environ. 2009, 680, 70–77. [Google Scholar] [CrossRef] [PubMed]
  294. Horvathova, E.; Navarova, J.; Galova, E.; Sevcovicova, A.; Chodakova, L.; Snahnicanova, Z.; Melusova, M.; Kozics, K.; Slamenova, D. Assessment of Antioxidative, Chelating, and DNA-Protective Effects of Selected Essential Oil Components (Eugenol, Carvacrol, Thymol, Borneol, Eucalyptol) of Plants and Intact Rosmarinus officinalis Oil. J. Agric. Food Chem. 2014, 62, 6632–6639. [Google Scholar] [CrossRef] [PubMed]
  295. El-Sayed, E.S.M.; Mansour, A.M.; Abdul-Hameed, M.S. Thymol and Carvacrol Prevent Doxorubicin-Induced Cardiotoxicity by Abrogation of Oxidative Stress, Inflammation, and Apoptosis in Rats. J. Biochem. Mol. Toxic. 2016, 30, 37–44. [Google Scholar] [CrossRef] [PubMed]
  296. Calo, R.; Visone, C.M.; Marabini, L. Thymol and Thymus Vulgaris L. activity against UVA- and UVB-induced damage in NCTC 2544 cell line. Mutat. Res. Gen. Tox. En. 2015, 791, 30–37. [Google Scholar] [CrossRef] [PubMed]
  297. Kazemi, M.; Rostami, H. Chemical composition and biological activities of Iranian Achillea wilhelmsii L. essential oil: A high effectiveness against Candida spp. and Escherichia strains. Nat. Prod. Res. 2015, 29, 286–288. [Google Scholar] [CrossRef] [PubMed]
  298. Alitonou, G.; Tchobo, F.; Avlessi, F.; Sohounhloue, D.K.; Menut, C. Aeollanthus pubescens Benth. from Benin: A Potential Source of Essential Oil with High Antiradical Efficiency. J. Essent. Oil Bear. Plants 2013, 16, 308–314. [Google Scholar] [CrossRef]
  299. Kavoosi, G.; Teixeira da Silva, J.A.; Saharkhiz, M.J. Inhibitory effects of Zataria multiflora essential oil and its main components on nitric oxide and hydrogen peroxide production in glucose-stimulated human monocyte. Food Chem. Toxicol. 2012, 50, 3079–3085. [Google Scholar] [CrossRef] [PubMed]
  300. Ribeiro, A.R.S.; Diniz, P.B.F.; Pinheiro, M.S.; Albuquerque-Júnior, R.C.L.; Thomazzi, S.M. Gastroprotective effects of thymol on acute and chronic ulcers in rats: The role of prostaglandins, ATP-sensitive K+ channels, and gastric mucus secretion. Chem.-Biol. Interact. 2016, 244, 121–128. [Google Scholar] [CrossRef] [PubMed]
  301. García, D.A.; Bujons, J.; Vale, C.; Suñol, C. Allosteric positive interaction of thymol with the GABAA receptor in primary cultures of mouse cortical neurons. Neuropharmacology 2006, 50, 25–35. [Google Scholar] [CrossRef] [PubMed]
  302. Saravanan, S.; Pari, L. Role of thymol on hyperglycemia and hyperlipidemia in high fat diet-induced type 2 diabetic C57BL/6J mice. Eur. J. Pharmacol. 2015, 761, 279–287. [Google Scholar] [CrossRef] [PubMed]
  303. Saravanan, S.; Pari, L. Protective effect of thymol on high fat diet induced diabetic nephropathy in C57BL/6J mice. Chem.-Biol. Interact. 2016, 245, 1–11. [Google Scholar] [CrossRef] [PubMed]
  304. Basch, E.; Ulbricht, C.; Hammerness, P.; Bevins, A.; Sollars, D. Thyme (Thymus vulgaris L.), thymol. J. Herb. Pharmacother. 2004, 4, 49–67. [Google Scholar] [CrossRef] [PubMed]
  305. Oh, J.; Bowling, J.J.; Carroll, J.F.; Demirci, B.; Başer, K.H.C.; Leininger, T.D.; Bernier, U.R.; Hamann, M.T. Natural product studies of U.S. endangered plants: Volatile components of Lindera melissifolia (Lauraceae) repel mosquitoes and ticks. Phytochemistry 2012, 80, 28–36. [Google Scholar] [CrossRef] [PubMed]
  306. Park, S.N.; Lim, Y.K.; Freire, M.O.; Cho, E.; Jin, D.; Kook, J.K. Antimicrobial effect of linalool and α-terpineol against periodontopathic and cariogenic bacteria. Anaerobe 2012, 18, 369–372. [Google Scholar] [CrossRef] [PubMed]
  307. Bader, A.; Panizzi, L.; Cioni, P.L.; Flamini, G. Achillea ligustica: Composition and antimicrobial activity of essential oils from the leaves, flowers and some pure constituents. Cent. Eur. J. Biol. 2007, 2, 206–212. [Google Scholar] [CrossRef]
  308. Ellouze, I.; Abderrabba, M.; Sabaou, N.; Mathieu, F.; Lebrihi, A.; Bouajila, J. Seasonal variation impact on Citrus aurantium leaves essential oil: Chemical composition and biological activities. J. Food Sci. 2012, 77, 173–180. [Google Scholar] [CrossRef] [PubMed]
  309. Müller, G.C.; Junnila, A.; Butler, J.; Kravchenko, V.D.; Revay, E.E.; Weiss, R.W.; Schlein, Y. Efficacy of the botanical repellents geraniol, linalool, and citronella against mosquitoes. J. Vector Ecol. 2009, 34, 2–8. [Google Scholar] [CrossRef] [PubMed]
  310. Yang, F.; Long, E.; Wen, J.; Cao, L.; Zhu, C.; Hu, H.; Ruan, Y.; Okanurak, K.; Hu, H.; Wei, X.; et al. Linalool, derived from Cinnamomum camphora (L.) Presl leaf extracts, possesses molluscicidal activity against Oncomelania hupensis and inhibits infection of Schistosoma japonicum. Parasite Vector 2014, 7, 407. [Google Scholar] [CrossRef] [PubMed]
  311. Peana, A.T.; De Montis, M.G.; Sechi, S.; Sircana, G.; D’Aquila, P.S.; Pippia, P. Effects of (−)‑linalool in the acute hyperalgesia induced by carrageenan, l-glutamate and prostaglandin E2. Eur. J. Pharmacol. 2004, 497, 279–284. [Google Scholar] [CrossRef] [PubMed]
  312. Huo, M.; Cui, X.; Xue, J.; Chi, G.; Gao, R.; Deng, X.; Guan, S.; Wei, J.; Soromou, L.W.; Feng, H.; et al. Anti-inflammatory effects of linalool in RAW 264.7 macrophages and lipopolysaccharide-induced lung injury model. J. Surg. Res. 2013, 180, e47–e54. [Google Scholar] [CrossRef] [PubMed]
  313. Ma, J.; Xu, H.; Wu, J.; Qu, C.; Sun, F.; Xu, S. Linalool inhibits cigarette smoke-induced lung inflammation by inhibiting NF-κB activation. Int. Immunopharmacol. 2015, 29, 708–713. [Google Scholar] [CrossRef] [PubMed]
  314. Loizzo, M.R.; Tundis, R.; Menichini, F.; Saab, A.M.; Statti, G.A. Antiproliferative effects of essential oils and their major constituents in human renal adenocarcinoma and amelanotic melanoma cells. Cell Prolif. 2008, 41, 1002–1012. [Google Scholar] [CrossRef] [PubMed]
  315. Gu, Y.; Ting, Z.; Qiu, X.; Zhang, X.; Gan, X.; Fang, Y.; Xu, X.; Xu, R. Linalool preferentially induces robust apoptosis of a variety of leukemia cells via upregulating p53 and cyclin-dependent kinase inhibitors. Toxicology 2010, 268, 19–24. [Google Scholar] [CrossRef] [PubMed]
  316. Maeda, H.; Yamazaki, M.; Katagata, Y. Kuromoji (Lindera umbellata) essential oil-induced apoptosis and differentiation in human leukemia HL-60 cells. Exp. Ther. Med. 2012, 3, 49–52. [Google Scholar] [CrossRef] [PubMed]
  317. Chang, M.Y.; Shieh, D.E.; Chen, C.C.; Yeh, C.S.; Dong, H.P. Linalool Induces Cell Cycle Arrest and Apoptosis in Leukemia Cells and Cervical Cancer Cells through CDKIs. Int. J. Mol. Sci. 2015, 16, 28169–28179. [Google Scholar] [CrossRef] [PubMed]
  318. Cho, S.Y.; Jun, H.J.; Lee, J.H.; Jia, Y.; Kim, K.H.; Lee, S.J. Linalool reduces the expression of 3-hydroxy-3-methylglutaryl CoA reductase via sterol regulatory element binding protein-2- and ubiquitin-dependent mechanisms. FEBS Lett. 2011, 585, 3289–3296. [Google Scholar] [CrossRef] [PubMed]
  319. Kladniew, B.R.; Polo, M.; Villegas, S.M.; Galle, M.; Crespo, R.; de Bravo, M.G. Synergistic antiproliferative and anticholesterogenic effects of linalool, 1,8-cineole, and simvastatin on human cell lines. Chem.-Biol. Interact. 2014, 214, 57–68. [Google Scholar] [CrossRef] [PubMed]
  320. Linck, V.M.; Da Silva, A.L.; Figueiró, M.; Caramão, E.B.; Moreno, P.R.H.; Elisabetsky, E. Effects of inhaled Linalool in anxiety, social interaction and aggressive behavior in mice. Phytomedicine 2010, 17, 679–683. [Google Scholar] [CrossRef] [PubMed]
  321. Guzman-Gutierrez, S.L.; Gomez-Cansino, R.; Garcia-Zebadua, J.C.; Jimenez-Perez, N.C.; Reyes-Chilpa, R. Antidepressant activity of Litsea glaucescens essential oil: Identification of β-pinene and linalool as active principles. J. Ethnopharmacol. 2012, 143, 673–679. [Google Scholar] [CrossRef] [PubMed]
  322. Kessler, A.; Sahin-Nadeem, H.; Lummis, S.C.R.; Weigel, I.; Pischetsrieder, M.; Buettner, A.; Villmann, C. GABAA receptor modulation by terpenoids from Sideritis extracts. Mol. Nutr. Food Res. 2014, 58, 851–862. [Google Scholar] [CrossRef] [PubMed]
  323. Park, T.J.; Park, Y.S.; Lee, T.G.; Ha, H.; Kim, K.T. Inhibition of acetylcholine-mediated effects by borneol. Biochem. Pharmacol. 2003, 65, 83–90. [Google Scholar] [CrossRef]
  324. Horvathova, E.; Slamenova, D.; Marsalkova, L.; Sramkova, M.; Wsolova, L. Effects of borneol on the level of DNA damage induced in primary rat hepatocytes and testicular cells by hydrogen peroxide. Food Chem. Toxicol. 2009, 47, 1318–1323. [Google Scholar] [CrossRef] [PubMed]
  325. Zhong, W.; Cui, Y.; Yu, Q.; Xie, X.; Liu, Y.; Wei, M.; Ci, X.; Peng, L. Modulation of LPS-Stimulated Pulmonary Inflammation by Borneol in Murine Acute Lung Injury Model. Inflammation 2014, 37, 1148–1157. [Google Scholar] [CrossRef] [PubMed]
  326. Juhás, S.; Cikos, S.; Czikkova, S.; Vesela, J.; Il’kova, G.; Hájek, T.; Domaracka, K.; Domaracky, M.; Bujnakova, D.; Rehák, P.; et al. Effects of Borneol and Thymoquinone on TNBS-Induced Colitis in Mice. Folia Biol. 2008, 54, 1–7. [Google Scholar]
  327. Qi, H.P.; Gao, X.C.; Zhang, L.Q.; Wei, S.Q.; Bi, S.; Yang, Z.C.; Cui, H. In vitro evaluation of enhancing effect of borneol on transcorneal permeation of compounds with different hydrophilicities and molecular sizes. Eur. J. Pharmacol. 2013, 705, 20–25. [Google Scholar] [CrossRef] [PubMed]
  328. Zhang, Q.; Wu, D.; Wu, J.; Ou, Y.; Mu, C.; Han, B.; Zhang, Q. Improved blood-brain barrier distribution: Effect of borneol on the brain pharmacokinetics of kaempferol in rats by in vivo microdialysis sampling. J. Ethnopharmacol. 2015, 162, 270–277. [Google Scholar] [CrossRef] [PubMed]
  329. Asili, J.; Emami, S.A.; Eynolghozat, R.; Noghab, Z.S.; Bazzaz, B.S.F.; Sahebkar, A. Chemical Composition and in Vitro Efficacy of Essential Oil of Seven Artemisia Species Against ESBL Producing Multidrug-Resistant Escherichia coli. J. Essent. Oil Bear. Plants 2015, 18, 124–145. [Google Scholar] [CrossRef]
  330. Silva-Filho, J.C.; Oliveira, N.N.; Arcanjo, D.D.; Quintans-Júnior, L.J.; Cavalcanti, S.C.; Santos, M.R.; Oliveira Rde, C.; Oliveira, A.P. Investigation of Mechanisms Involved in (−)‑Borneol-Induced Vasorelaxant Response on Rat Thoracic Aorta. Basic Clin. Pharmacol. Toxicol. 2012, 110, 171–177. [Google Scholar] [CrossRef] [PubMed]
  331. Granger, R.E.; Campbell, E.L.; Johnston, G.A.R. (+)- And (−)-borneol: efficacious positive modulators of GABA action at human recombinant α1β2γ2L GABAA receptors. Biochem. Pharmacol. 2005, 69, 1101–1111. [Google Scholar] [CrossRef] [PubMed]
  332. Su, J.; Lai, H.; Chen, J.; Li, L.; Wong, Y.S.; Chen, T.; Li, X. Natural Borneol, a Monoterpenoid Compound, Potentiates Selenocystine-Induced Apoptosis in Human Hepatocellular Carcinoma Cells by Enhancement of Cellular Uptake and Activation of ROS-Mediated DNA Damage. PLoS ONE 2013, 8, e63502. [Google Scholar] [CrossRef] [PubMed]
  333. Lin, A.L.; Shangari, N.; Chan, T.S.; Remirez, D.; O’Brien, P.J. Herbal monoterpene alcohols inhibit propofol metabolism and prolong anesthesia time. Life Sci. 2006, 79, 21–29. [Google Scholar] [CrossRef] [PubMed]
  334. Letessier, M.P.; Svoboda, K.P.; Walters, D.R. Antifungal Activity of the Essential Oil of Hyssop (Hyssopus officinalis). J. Phytopathol. 2001, 149, 673–678. [Google Scholar] [CrossRef]
  335. Chen, N.; Sun, G.; Yuan, X.; Hou, J.; Wu, Q.; Soromou, L.W.; Feng, H. Inhibition of lung inflammatory responses by bornyl acetate is correlated with regulation of myeloperoxidase activity. J. Surg. Res. 2014, 186, 436–455. [Google Scholar] [CrossRef] [PubMed]
  336. Yang, H.; Zhao, R.; Chen, H.; Jia, P.; Bao, L.; Tang, H. Bornyl Acetate Has an Anti-inflammatory Effect in Human Chondrocytes Via Induction of IL-11. IUBMB Life 2014, 66, 854–859. [Google Scholar] [CrossRef] [PubMed]
  337. Wang, X.; Ma, A.; Shi, W.; Geng, M.; Zhong, X.; Zhao, Y. Quercetin and Bornyl Acetate Regulate T-Lymphocyte Subsets and INF-γ/IL-4 Ratio In Utero in Pregnant Mice. Evid.-Based Complement. Altern. Med. 2011, 745262. [Google Scholar] [CrossRef]
  338. Yan, R.; Yang, Y.; Zou, G. Cytotoxic and apoptotic effects of Lindera strychnifolia leaf essential oil. J. Essent. Oil Res. 2014, 26, 308–314. [Google Scholar] [CrossRef]
  339. Silva, L.L.; Garlet, Q.I.; Benovit, S.C.; Dolci, G.; Mallmann, C.A.; Bürger, M.E.; Baldisserotto, B.; Longhi, S.J.; Heinzmann, B.M. Sedative and anesthetic activities of the essential oils of Hyptis mutabilis (Rich.) Briq. and their isolated components in silver catfish (Rhamdia quelen). Braz. J. Med. Biol. Res. 2013, 46, 771–779. [Google Scholar] [CrossRef] [PubMed]
  340. Nobrega, F.F.F.; Salvadori, M.G.S.S.; Masson, C.J.; Mello, C.F.; Nascimento, T.S.; Leal-Cardoso, J.H.; de Sousa, D.P.; Almeida, R.N. Monoterpenoid terpinen-4-ol exhibits anticonvulsant activity in behavioural and electrophysiological studies. Oxid. Med. Cell. Longev. 2014, 2014, 703848. [Google Scholar] [CrossRef] [PubMed]
  341. Aoshima, H.; Oda, K.; Orihara, Y.; Hara, A.; Shigemori, Y.; Tan, N.; Koda, H.; Kiso, Y. Effects of essential oils on the response of GABAA receptors, sleeping time in mice induced by sleeping drug and plasma adrenocorticotropic hormone levels of rats. Aroma Res. 2009, 10, 58–64. [Google Scholar]
  342. Maia-Joca, R.P.M.; Joca, H.C.; Ribeiro, F.J.P.; do Nascimento, R.V.; Silva-Alves, K.S.; Cruz, J.S.; Coleho-de-Souza, A.N.; Leal-Cardoso, J.H. Investigation of Terpinen-4-ol Effects on Vascular Smooth Muscle Relaxation. Life Sci. 2014, 115, 52–58. [Google Scholar] [CrossRef] [PubMed]
  343. Bozzuto, G.; Colone, M.; Toccacieli, L.; Stringaro, A.; Molinari, A. Tea tree oil might combat melanoma. Planta Med. 2011, 77, 54–56. [Google Scholar] [CrossRef] [PubMed]
  344. Greay, S.J.; Ireland, D.J.; Kissick, H.T.; Levy, A.; Beilharz, M.W.; Riley, T.V.; Carson, C.F. Induction of necrosis and cell cycle arrest in murine cancer cell lines by Melaleuca alternifolia (tea tree) oil and terpinen-4-ol. Cancer Chemoth. Pharm. 2010, 65, 877–888. [Google Scholar] [CrossRef] [PubMed]
  345. Wu, C.S.; Chen, Y.J.; Chen, J.J.W.; Shieh, J.J.; Huang, C.H.; Lin, P.S.; Chang, G.C.; Chang, J.T.; Lin, C.C. Terpinen-4-ol Induces Apoptosis in Human Nonsmall Cell Lung Cancer in Vitro and in Vivo. Evid. Based Complement. Altern. Med. 2012, 12, 818261. [Google Scholar] [CrossRef] [PubMed]
  346. Calcabrini, A.; Stringaro, A.; Toccacieli, L.; Meschini, S.; Marra, M.; Colone, M.; Salvatore, G.; Mondello, F.; Arancia, G.; Molinari, A. Terpinen-4-ol, the main component of Melaleuca alternifolia (tea tree) oil inhibits the in vitro growth of human melanoma cells. J. Investig. Dermatol. 2004, 122, 349–360. [Google Scholar] [CrossRef] [PubMed]
  347. Ninomiya, K.; Hayama, K.; Ishijima, S.A.; Maruyama, N.; Irie, H.; Kurihara, J.; Abe, S. Suppression of inflammatory reactions by terpinen-4-ol, a main constituent of tea tree oil, in a murine model of oral candidiasis and its suppressive activity to cytokine production of macrophages in vitro. Biol. Pharm. Bull. 2013, 36, 838–844. [Google Scholar] [CrossRef] [PubMed]
  348. Hart, P.H.; Brand, C.; Carson, C.F.; Riley, T.V.; Prager, R.H.; Finlay-Jones, J.J. Terpinen-4-ol, the main component of the essential oil of Melaleuca alternifolia (tea tree oil), suppresses inflammatory mediator production by activated human monocytes. Inflamm. Res. 2000, 49, 619–626. [Google Scholar] [CrossRef] [PubMed]
  349. Loughlin, R.; Gilmore, B.F.; McCarron, P.A.; Tunney, M.M. Comparison of the cidal activity of tea tree oil and terpinen-4-ol against clinical bacterial skin isolates and human fibroblast cells. Lett. Appl. Microbiol. 2008, 46, 428–433. [Google Scholar] [CrossRef] [PubMed]
  350. Hammer, K.A.; Carson, C.F.; Riley, T.V. Antifungal activity of the components of Melaleuca alternifolia (tea tree) oil. J. Appl. Microbiol. 2003, 95, 853–860. [Google Scholar] [CrossRef] [PubMed]
  351. You, C.; Guo, S.; Zhang, W.; Yang, K.; Geng, Z.; Du, S.; Wang, C.; Deng, Z. Identification of repellent and insecticidal constituents from Artemisia mongolica essential oil against Lasioderma serricorne. J. Chem. 2015, 2015. [Google Scholar] [CrossRef]
  352. Cosentino, S.; Tuberoso, C.I.G.; Pisano, B.; Satta, M.L.; Mascia, V.; Arzedi, E.; Palmas, F. In-vitro antimicrobial activity and chemical composition of Sardinian Thymus essential oils. Lett. Appl. Microbiol. 1999, 29, 130–135. [Google Scholar] [CrossRef] [PubMed]
  353. Has, A.T.C.; Islam, M.R.; Baburin, I.; Hering, S.; Osman, H.; Mohamad, H.; Abdullah, J.M. The inhibitory activity of nutmeg essential oil on GABAA α1β2γ2s receptors. Biomed. Res. 2014, 25, 543–550. [Google Scholar]
  354. Quintans-Júnior, L.J.; Oliveira, M.G.; Santana, M.F.; Santana, M.T.; Guimarães, A.G.; Siqueira, J.S.; de Sousa, D.P.; Almeida, R.N. α-Terpineol reduces nociceptive behavior in mice. Pharm. Biol. 2011, 49, 583–586. [Google Scholar] [CrossRef] [PubMed]
  355. Mulyaningsih, S.; Sporer, F.; Reichling, J.; Wink, M. Antibacterial activity of essential oils from Eucalyptus and of selected components against multidrug-resistant bacterial pathogens. Pharm. Biol. 2011, 49, 893–899. [Google Scholar] [CrossRef] [PubMed]
  356. Klein, G.; Rüben, C.; Upmann, M. Antimicrobial Activity of Essential Oil Components Against Potential Food Spoilage Microorganisms. Curr. Microbiol. 2013, 67, 200–208. [Google Scholar] [CrossRef] [PubMed]
  357. Bagamboula, C.F.; Uyttendaele, M.; Debereve, J. Inhibitory effect of thyme and basil essential oils, carvacrol, thymol, estragol, linalool and p-cymene towards Shigella sonnei and S. flexneri. Food Microbiol. 2004, 21, 33–42. [Google Scholar] [CrossRef]
  358. Ultee, A.; Slump, R.A.; Steging, G.; Smid, E.J. Antimicrobial activity of carvacrol toward Bacillus cereus on rice. J. Food Prot. 2000, 63, 620–624. [Google Scholar] [PubMed]
  359. Sanchez, C.; Aznar, R.; Sanchez, G. The effect of carvacrol on enteric viruses. Int. J. Food Microbiol. 2015, 192, 72–76. [Google Scholar] [CrossRef] [PubMed]
  360. Arunasree, K.M. Anti-proliferative effects of carvacrol on a human metastatic breast cancer cell line, MDA-MB 231. Phytomedicine 2010, 17, 581–588. [Google Scholar] [CrossRef] [PubMed]
  361. Bhakkiyalakshmi, E.; Suganya, N.; Sireesh, D.; Krishnamurthi, K.; Devi, S.S.; Rajaguru, P.; Ramkumar, K.M. Carvacrol induces mitochondria-mediated apoptosis in HL-60 promyelocytic and Jurkat T lymphoma cells. Eur. J. Pharmacol. 2016, 772, 92–98. [Google Scholar] [CrossRef] [PubMed]
  362. Llana-Ruiz‑Cabello, M.; Gutierrez‑Praena, D.; Pichardo, S.; Moreno, F.J.; Bermúdez, J.M.; Aucejo, S.; Cameán, A.M. Cytotoxicity and morphological effects induced by carvacrol and thymol on the human cell line Caco-2. Food Chem. Toxicol. 2014, 64, 281–290. [Google Scholar] [CrossRef] [PubMed]
  363. Zeytinoglu, H.; Incesu, Z.; Baser, K.H.C. Inhibition of DNA synthesis by carvacrol in mouse myoblast cells bearing a human N-RAS oncogene. Phytomedicine 2003, 10, 292–299. [Google Scholar] [CrossRef] [PubMed]
  364. Lima, M.S.; Quintans-Júnior, L.J.; de Santana, W.A.; Kaneto, C.M.; Soares, M.B. P.; Villarreal, C.F. Anti-inflammatory effects of carvacrol: Evidence for a key role of interleukin-10. Eur. J. Pharmacol. 2013, 699, 112–117. [Google Scholar] [CrossRef] [PubMed]
  365. Melo, F.H.C.; Venâncio, E.T.; de Sousa, D.P.; de França Fonteles, M.M.; de Vasconcelos, S.M.M.; Viana, G.S.B.; de Sousa, F.C.F. Anxiolytic-like effect of Carvacrol (5-isopropyl-2-methylphenol) in mice: Involvement with GABAergic transmission. Fund. Clin. Pharmacol. 2010, 24, 437–443. [Google Scholar] [CrossRef] [PubMed]
  366. Boskabady, M.H.; Mahtaj, L.G. Lung inflammation changes and oxidative stress induced by cigarette smoke exposure in guinea pigs affected by Zataria multiflora and its constituent, carvacrol. BMC Complement. Altern. Med. 2015, 15. [Google Scholar] [CrossRef] [PubMed]
  367. Melo, F.H.C.; Rios, E.R.V.; Rocha, N.F.M.; Citó, M.C.O.; Fernandes, M.L.; de Sousa, D.P.; de Vasconcelos, S.M.M.; de Sousa, F.C.F. Antinociceptive activity of carvacrol (5-isopropyl-2-methylphenol) in mice. J. Pharm. Pharmacol. 2012, 64, 1722–1729. [Google Scholar] [CrossRef] [PubMed]
  368. Jukic, M.; Politeo, O.; Maksimovic, M.; Milos, M.; Milos, M. In vitro acetylcholinesterase inhibitory properties of thymol, carvacrol and their derivatives thymoquinone and thymohydroquinone. Phytother. Res. 2007, 21, 259–261. [Google Scholar] [CrossRef] [PubMed]
  369. Friedman, M. Chemistry and multibeneficial bioactivities of carvacrol (4-isopropyl-2-methylphenol), a component of essential oils produced by aromatic plants and spices. J. Agric. Food Chem. 2014, 62, 7652–7670. [Google Scholar] [CrossRef] [PubMed]
  370. Baser, K.H.C. Biological and pharmacological activities of carvacrol and carvacrol bearing essential oils. Curr. Pharm. Des. 2008, 14, 3106–3119. [Google Scholar] [CrossRef] [PubMed]
  371. Andre, W.P.P.; Ribeiro, W.L.C.; Cavalcante, G.S.; dos Santos, J.M.L.; Macedo, I.T.F.; de Paula, H.C.B.; de Freitas, R.M.; de Morais, S.M.; de Melo, J.V.; Bevilaqua, C.M.L. Comparative efficacy and toxic effects of carvacryl acetate and carvacrol on sheep gastrointestinal nematodes and mice. Vet. Parasitol. 2016, 218, 52–58. [Google Scholar] [CrossRef] [PubMed]
  372. Damasceno, S.R.B.; Oliveira, F.R.A.; Carvalho, N.S.; Brito, C.F.; Silva, I.S.; Sousa, F.B.M.; Silva, R.O.; Sousa, D.P.; Barbosa, A.L.R.; Freitas, R.M.; et al. Carvacryl acetate, a derivative of carvacrol, reduces nociceptive and inflammatory response in mice. Life Sci. 2014, 94, 58–66. [Google Scholar] [CrossRef] [PubMed]
  373. Pires, L.F.; Costa, L.M.; Cardoso de Almeida, A.A.; Silva, O.A.; Santos Cerqueira, G.; de Sousa, D.P.; Pires, R.M.; Satyal, P.; de Freitas, R.M. Neuropharmacological effects of carvacryl acetate on δ-aminolevulinic dehydratase, Na+, K+-ATPase activities and amino acids levels in mice hippocampus after seizures. Chem. Biol. Interact. 2015, 226, 49–57. [Google Scholar] [CrossRef] [PubMed]
  374. Pires, L.F.; Costa, L.M.; Silva, O.A.; Cerqueira, G.S.; de Sousa, D.P.; de Freitas, R.M. Anxiolytic-like effects of carvacryl acetate, a derivative of carvacrol, in mice. Pharmacol. Biochem. Behav. 2013, 112, 42–48. [Google Scholar] [CrossRef] [PubMed]
  375. Omolo, M.O.; Okinyo, D.; Ndiege, I.O.; Lwande, W.; Hassanali, A. Repellency of essential oils of some Kenyan plants against Anopheles gambiae. Phytochemistry 2004, 65, 2797–2802. [Google Scholar] [CrossRef] [PubMed]
  376. Choi, I.Y.; Lim, J.H.; Hwang, S.; Lee, J.C.; Cho, G.S.; Kim, W.K. Anti-ischemic and anti-inflammatory activity of (S)-cis-verbenol. Free Radical Res. 2010, 44, 541–551. [Google Scholar] [CrossRef] [PubMed]
  377. Kubo, I.; Kinst-Hori, I. Tyrosinase Inhibitors from Cumin. J. Agric. Food Chem. 1998, 46, 5338–5341. [Google Scholar] [CrossRef]
  378. Nitoda, T.; Fan, M.D.; Kubo, I. Effects of Cuminaldehyde on Melanoma Cells. Phytother. Res. 2008, 22, 809–813. [Google Scholar] [CrossRef] [PubMed]
  379. Kalpoutzakis, E.; Aligiannis, N.; Mentis, A.; Mitaku, S.; Charvala, C. Composition of the essential oil of two Nepeta species and in vitro evaluation of their activity against Helicobacter pylori. Planta Med. 2001, 67, 880–883. [Google Scholar] [CrossRef] [PubMed]
  380. Birkett, M.A.; Hassanali, A.; Hoglund, S.; Pettersson, J.; Pickett, J.A. Repellent activity of catmint, Nepeta cataria, and iridoid nepetalactone isomers against Afro-tropical mosquitoes, ixodid ticks and red poultry mites. Phytochemistry 2011, 72, 109–114. [Google Scholar] [CrossRef] [PubMed]
  381. Bruce, T.J.A.; Birkett, M.A.; Blande, J.; Hooper, A.M.; Martin, J.L.; Khambay, B.; Prosser, I.; Smart, L.E.; Wadhams, L.J. Response of economically important aphids to components of Hemizygia petiolata essential oil. Pest Manag. Sci. 2005, 61, 1115–1121. [Google Scholar] [CrossRef] [PubMed]
  382. Santos, T.G.; Dognini, J.; Begnini, I.M.; Rebelo, R.A.; Verdi, M.; de Gasper, A.L.; Dalmarco, E.M. Chemical characterization of essential oils from Drimys angustifolia Miers (Winteraceae) and antibacterial activity of their major compounds. J. Braz. Chem. Soc. 2013, 24, 164–170. [Google Scholar] [CrossRef]
  383. Nascimento, A.M.A.; Brandao, M.G.L.; Oliveira, G.B.; Fortes, I.C.; Chartone-Souza, E. Synergistic bactericidal activity of Eremanthus erythropappus oil or β-bisabolene with ampicillin against Staphylococcus aureus. Antonie Leeuwenhoek 2007, 92, 95–100. [Google Scholar] [CrossRef] [PubMed]
  384. Cakir, A.; Kordali, S.; Zengin, H.; Izumi, S.; Hirata, T. Composition and antifungal activity of essential oils isolated from Hypericum hyssopifolium and Hypericum heterophyllum. Flavour Fragr. J. 2004, 19, 62–68. [Google Scholar] [CrossRef]
  385. Ulubelen, A.; Topcu, G.; Eriş, C.; Sönmez, U.; Kartal, M.; Kurucu, S.; Bozok-Johansson, C. Terpenoids from Salvia sclarea. Phytochemistry 1994, 36, 971–974. [Google Scholar] [CrossRef]
  386. Chavan, M.J.; Wakte, P.S.; Shinde, D.B. Analgesic and anti-inflammatory activity of caryophyllene oxide from Annona squamosa L. bark. Phytomedicine 2010, 17, 149–151. [Google Scholar] [CrossRef] [PubMed]
  387. Sibanda, S.; Chigwada, G.P.; Melvin, G.; Gwebu, E.T.; Noletto, J.A.; Schmidt, J.M.; Rea, A.I.; Setzer, W.N. Composition and bioactivity of the leaf essential oil of Heteropyxis dehniae from Zimbabwe. J. Ethnopharmacol. 2004, 92, 107–111. [Google Scholar] [CrossRef] [PubMed]
  388. Park, K.R.; Nam, D.; Yun, H.M.; Lee, S.G.; Jang, H.J.; Sethi, G.; Cho, S.K.; Ahn, K.S. β-Caryophyllene oxide inhibits growth and induces apoptosis through the suppression of PI3K/AKT/mTOR/S6K1 pathways and ROS-mediated MAPKs activation. Cancer Lett. 2011, 312, 178–188. [Google Scholar] [CrossRef] [PubMed]
  389. Leal, S.M.; Pino, N.; Stashenko, E.E.; Martínez, J.R.; Escobar, P. Antiprotozoal activity of essential oils derived from Piper spp. grown in Colombia. J. Essent. Oil Res. 2013, 25, 512–519. [Google Scholar] [CrossRef]
  390. Zhang, W.J.; You, C.X.; Yang, K.; Chen, R.; Wang, Y.; Wu, Y.; Geng, Z.F.; Chen, H.P.; Jiang, H.Y.; Su, Y.; et al. Bioactivity of essential oil of Artemisia argyi Levl. et Van. and its main compounds against Lasioderma serricorne. J. Oleo Sci. 2014, 63, 829–837. [Google Scholar] [CrossRef] [PubMed]
  391. Basha, R.H.; Sankaranarayanan, C. β-Caryophyllene, a natural sesquiterpene lactone attenuates hyperglycemia mediated oxidative and inflammatory stress in experimental diabetic rats. Chem.-Biol. Interact. 2016, 245, 50–58. [Google Scholar] [CrossRef] [PubMed]
  392. Calleja, M.A.; Vieites, J.M.; Montero-Melendez, T.; Torres, M.I.; Faus, M.J.; Gil, A.; Suárez, A. The antioxidant effect of β‑caryophyllene protects rat liver from carbon tetrachloride-induced fibrosis by inhibiting hepatic stellate cell activation. Brit. J. Nutr. 2013, 109, 394–401. [Google Scholar] [CrossRef] [PubMed]
  393. Fernandes, E.S.; Passos, G.F.; Medeiros, R.; da Cunha, F.M.; Ferreira, J.; Campos, M.M.; Pianowski, L.F.; Calixto, J.B. Anti-inflammatory effects of compounds α-humulene and (−)-trans-caryophyllene isolated from the essential oil of Cordia verbenacea. Eur. J. Pharmacol. 2007, 569, 228–236. [Google Scholar] [CrossRef] [PubMed]
  394. Passos, G.F.; Fernandes, E.S.; da Cunha, F.M.; Ferreira, J.; Pianowski, L.F.; Campos, M.M.; Calixto, J.B. Anti-inflammatory and anti-allergic properties of the essential oil and active compounds from Cordia verbenacea. J. Ethnopharmacol. 2007, 110, 323–333. [Google Scholar] [CrossRef] [PubMed]
  395. Kubo, I.; Muroi, H.; Kubo, A. Naturally occurring antiacne agents. J. Nat. Prod. 1994, 57, 9–17. [Google Scholar] [CrossRef] [PubMed]
  396. Loizzo, M.R.; Tundis, R.; Menichini, F.; Saab, A.M.; Statti, G.A.; Menichini, F. Cytotoxic activity of essential oils from Labiatae and Lauraceae families against in vitro human tumor models. Anticancer Res. 2007, 27, 3293–3300. [Google Scholar] [PubMed]
  397. Sylvestre, M.; Longtin, A.P.A.; Legault, J. Volatile leaf constituents and anticancer activity of Bursera simaruba (L.) Sarg. essential oil. Nat. Prod. Commun. 2007, 2, 1273–1276. [Google Scholar]
  398. Sylvestre, M.; Pichette, A.; Longtin, A.; Nagau, F.; Legault, J. Essential oil analysis and anticancer activity of leaf essential oil of Croton flavens L. from Guadeloupe. J. Ethnopharmacol. 2006, 103, 99–102. [Google Scholar] [CrossRef] [PubMed]
  399. Sylvestre, M.; Pichette, A.; Lavoie, S.; Longtin, A.; Legault, J. Composition and cytotoxic activity of the leaf essential oil of Comptonia peregrina (L.) Coulter. Phytother. Res. 2007, 21, 536–540. [Google Scholar] [CrossRef] [PubMed]
  400. Venditti, A.; Bianco, A.; Nicoletti, M.; Quassinti, L.; Bramucci, M.; Lupidi, G.; Vitali, L.A.; Petrelli, D.; Papa, F.; Vittori, S.; et al. Phytochemical analysis, biological evaluation and micromorphological study of Stachys alopecuros (L.) Benth. subsp. divulsa (Ten.) Grande endemic to central Apennines, Italy. Fitoterapia 2013, 90, 94–103. [Google Scholar] [PubMed]
  401. Tundis, R.; Peruzzi, L.; Menichini, F. Phytochemical and biological studies of Stachys species in relation to chemotaxonomy: A review. Phytochemistry 2014, 102, 7–39. [Google Scholar] [CrossRef] [PubMed]
  402. Pérez-López, A.; Cirio, A.T.; Rivas-Galindo, V.M.; Waksman de Torres, N. Activity against Streptococcus pneumoniae of the essential oil and δ-cadinene isolated from Schinus molle fruit. J. Essent. Oil Res. 2011, 23, 25–28. [Google Scholar] [CrossRef]
  403. Zheljazkov, V.D.; Cantrell, C.L.; Tekwani, B.; Khan, S.I. Content, Composition, and Bioactivity of the Essential Oils of Three Basil Genotypes as a Function of Harvesting. J. Agric. Food Chem. 2008, 56, 380–385. [Google Scholar] [CrossRef] [PubMed]
  404. Chang, S.T.; Chen, P.F.; Wang, S.Y.; Wu, H.H. Antimite activity of essential oils and their constituents from Taiwania cryptomerioides. J. Med. Entomol. 2001, 38, 455–457. [Google Scholar] [CrossRef] [PubMed]
  405. Chang, S.T.; Wang, S.Y.; Wu, C.L.; Chen, P.F.; Kuo, Y.H. Comparison of the antifungal activity of cadinane skeletal sesquiterpenoids from Taiwania (Taiwania cryptomerioides Hayata) heartwood. Holzforschung 2000, 54, 241–245. [Google Scholar] [CrossRef]
  406. Ho, C.L.; Liao, P.C.; Su, Y.C. Composition and antimicrobial activities of the leaf essential oil of Machilus zuihoensis from Taiwan. Rev. Bras. Farmacogn. 2012, 22, 277–283. [Google Scholar] [CrossRef]
  407. Jeong, J.B.; Choi, J.; Lou, Z.; Jiang, X.; Lee, S.H. Patchouli alcohol, an essential oil of Pogostemon cablin, exhibits anti-tumorigenic activity in human colorectal cancer cells. Int. Immunopharmacol. 2013, 16, 184–190. [Google Scholar] [CrossRef] [PubMed]
  408. Xian, Y.F.; Li, Y.C.; Ip, S.P.; Lin, Z.X.; Lai, X.P.; Su, Z.R. Anti-inflammatory effect of patchouli alcohol isolated from Pogostemonis Herba in LPS-stimulated RAW264.7 macrophages. Exp. Ther. Med. 2011, 2, 545–550. [Google Scholar] [PubMed]
  409. Li, Y.C.; Xian, Y.F.; Ip, S.P.; Su, Z.R.; Su, J.Y.; He, J.J.; Xie, Q.F.; Lai, X.P.; Lin, Z.X. Anti-inflammatory activity of patchouli alcohol isolated from Pogostemonis Herba in animal models. Fitoterapia 2011, 82, 1295–1301. [Google Scholar] [CrossRef] [PubMed]
  410. Zheng, Y.F.; Xie, J.H.; Xu, Y.F.; Liang, Y.Z.; Mo, Z.Z.; Jiang, W.W.; Chen, X.Y.; Liu, Y.H.; Yu, X.D.; Huang, P.; et al. Gastroprotective effect and mechanism of patchouli alcohol against ethanol, indomethacin and stress-induced ulcer in rats. Chem.-Biol. Interact. 2014, 222, 27–36. [Google Scholar] [CrossRef] [PubMed]
  411. Prakasia, P.P.; Nair, A.S. Chemical fingerprint of essential oil components from fresh leaves of Glycosmis pentaphylla (Retz.) Correa. Pharma Innov. 2015, 3, 50–56. [Google Scholar]
  412. García, M.; Gonzales-Coloma, A.; Donadel, O.J.; Ardanaz, C.E.; Tonn, C.E.; Sosa, M.E. Insecticidal effects of Flourensia oolepis Blake (Asteraceae) essential oil. Biochem. Syst. Ecol. 2007, 35, 181–187. [Google Scholar] [CrossRef]
  413. Tavares, W.S.; Freitas, S.S.; Grazziotti, G.H.; Parente, L.M.L.; Lião, L.M.; Zanuncio, J.C. Ar-turmerone from Curcuma longa (Zingiberaceae) rhizomes and effects on Sitophilus zeamais (Coleoptera: Curculionidae) and Spodoptera frugiperda (Lepidoptera: Noctuidae). Ind. Crop Prod. 2013, 46, 158–164. [Google Scholar] [CrossRef]
  414. Lee, H.K.; Park, C.; Ahn, Y.J. Insecticidal activities of asarones identified in Acorus gramineus rhizome against Nilaparvata lugens (Homoptera: Delphacidae) and Plutella xylostella (Lepidoptera: Yponomeutoidae). Appl. Entomol. Zool. 2002, 37, 459–464. [Google Scholar] [CrossRef]
  415. Lee, H.S. Antiplatelet property of Curcuma longa L. rhizome-derived ar-turmerone. Bioresour. Technol. 2006, 97, 1372–1376. [Google Scholar] [CrossRef] [PubMed]
  416. Park, S.Y.; Jin, M.L.; Kim, Y.H.; Kim, Y.; Lee, S.J. Anti-inflammatory effects of aromatic-turmerone through blocking of NF-κB, JNK, and p38 MAPK signaling pathways in amyloid β-stimulated microglia. Int. Immunopharmacol. 2012, 14, 13–20. [Google Scholar] [CrossRef] [PubMed]
  417. Kumar, V. Turmeric (Curcuma longa): A valuable traditional medicine. Pharma Rev. 2006, 4, 77–80. [Google Scholar]
  418. Bakkali, F.; Averbeck, S.; Averbeck, D.; Idaomar, M. Biological effects of essential oils—A review. Food Chem. Toxicol. 2008, 46, 446–475. [Google Scholar] [CrossRef] [PubMed]
  419. Di Pasqua, R.; Betts, G.; Hoskins, N.; Edwards, M.; Ercolini, D.; Mauriello, G. Membrane toxicity of antimicrobial compounds from essential oils. J. Agric. Food Chem. 2007, 55, 4863–4870. [Google Scholar] [CrossRef] [PubMed]
  420. Sharopov, F.; Braun, M.S.; Gulmurodov, I.; Khalifaev, D.; Isupov, S.; Wink, M. Antimicrobial, Antioxidant, and Anti-Inflammatory Activities of Essential Oils of Selected Aromatic Plants from Tajikistan. Foods 2015, 4, 645–653. [Google Scholar] [CrossRef]
  421. Ipek, E.; Zeytinoglu, H.; Okay, S.; Tuylu, B.A.; Kurcuoglu, M.; Baser, K.H.C. Genotoxicity and antigenotoxicity of Origanum oil and carvacrol evaluated by Ames Salmonella/microsomal test. Food Chem. 2005, 93, 551–556. [Google Scholar] [CrossRef]
  422. Franzios, G.; Mirotsou, M.; Hatziapostolou, E.; Kral, J.; Scouras, Z.G.; Mavragani-Tsipidou, P. Insecticidal and genotoxic activities of mint essential oils. J. Agric. Food Chem. 1997, 45, 2690–2694. [Google Scholar] [CrossRef]
  423. Santana-Rios, G.; Orner, G.A.; Amantana, A.; Provost, C.; Wu, S.Y.; Dashwood, R.H. Potent antimutagenic activity of white tea in comparison with green tea in the Salmonella assay. Mutat. Res. 2001, 495, 61–74. [Google Scholar] [CrossRef]
  424. Cal, K. Skin penetration of terpenes from essential oils and topical vehicles. Planta Med. 2006, 72, 311–316. [Google Scholar] [CrossRef] [PubMed]
  425. Savelev, S.; Okello, E.; Perry, N.S.L.; Wilkins, R.M.; Perry, E.K. Synergistic and antagonistic interactions of anticholinesterase terpenoids in Salvia lavandulaefolia essential oil. Pharmacol. Biochem. Behav. 2003, 75, 661–668. [Google Scholar] [CrossRef]
  426. Aliakbarlu, J.; Shameli, F. In vitro antioxidant and antibacterial properties and total phenolic contents of essential oil from Thymus vulgaris, T. kotschyanus, Z. tenuior and Z. clinopodioides. Turk. J. Biochem. 2013, 38, 425–431. [Google Scholar] [CrossRef]
  427. Duru, M.E.; Oztürk, M.; Ugur, A.; Ceylan, Ö. The constituents of essential oil and in vitro antimicrobial activity of Micromeria cilicia from Turkey. J. Ethnopharmacol. 2004, 94, 43–48. [Google Scholar] [CrossRef] [PubMed]
  428. Sivropoulou, A.; Kokkini, S.; Lanaras, T.; Arsenakis, M. Antimicrobial activity of mint essential oils. J. Agric. Food Chem. 1995, 43, 2384–2388. [Google Scholar] [CrossRef]
  429. Radulovic, N.S.; Blagojevic, P.D.; Stojanovic-Radic, Z.Z.; Stojanovic, N.M. Antimicrobial Plant Metabolites: Structural Diversity and Mechanism of Action. Curr. Med. Chem. 2013, 20, 932–952. [Google Scholar] [CrossRef] [PubMed]
  430. Nowotarska, S.; Nowotarski, K.; Friedman, M. Effect of structure on the interactions between five natural antimicrobial compounds and phospholipids of bacterial cell membrane on model monolayers. Molecules 2014, 19, 7497–7515. [Google Scholar] [CrossRef] [PubMed]
  431. Helander, I.M.; Alakomi, H.; Latva-Kala, K.; Mattila-Sandholm, T.; Pol, I.; Smid, E.J.; Gorris, L.G.M.; von Wright, A. Characterization of the action of selected essential oil components on Gram-negative bacteria. J. Agric. Food Chem. 1998, 46, 3590–3595. [Google Scholar] [CrossRef]
  432. Lambert, R.J.W.; Skandamis, P.N.; Coote, P.J.; Nychas, G.J. A study of the minimum inhibitory concentration and mode of action of oregano essential oil, thymol and carvacrol. J. Appl. Microbiol. 2001, 91, 453–462. [Google Scholar] [CrossRef] [PubMed]
  433. Walsh, S.E.; Maillard, J.Y.; Russell, A.D.; Catrenich, C.E.; Charbonneau, D.L.; Bartolo, R.G. Activity and mechanisms of action of selected biocidal agents on Gram-positive and negative bacteria. J. Appl. Microbiol. 2003, 94, 240–247. [Google Scholar] [CrossRef] [PubMed]
  434. Horváth, G.; Kovács, K.; Kocsis, B.; Kustos, I. Effect of thyme (Thymus vulgaris L.) essential oil and its main constituents on the outer membrane protein composition of Erwinia strains studied with microfluid chip technology. Chromatographia 2009, 70, 1645–1650. [Google Scholar] [CrossRef]
  435. Di Pasqua, R.; Mamone, G.; Ferranti, P.; Ercolini, D.; Mauriello, G. Changes in the proteome of Salmonella enterica serovar Thompson as stress adaptation to sublethal concentrations of thymol. Proteomics 2010, 10, 1040–1049. [Google Scholar] [PubMed]
  436. Lachowicz, K.J.; Jones, G.P.; Briggs, D.R.; Bienvenu, F.E.; Wan, J.; Wilcock, A.; Coventry, M.J. The synergistic preservative effects of the essential oils of sweet basil (Ocimum basilicum L.) against acid-tolerant food microflora. Lett. Appl. Microbiol. 1998, 26, 209–214. [Google Scholar] [CrossRef] [PubMed]
  437. Moleyar, V.; Narasimham, P. Antibacterial activity of essential oil components. Int. J. Food Microbiol. 1992, 16, 337–342. [Google Scholar] [CrossRef]
  438. Mulyaningsih, S.; Sporer, F.; Zimmermann, S.; Reichling, J.; Wink, M. Synergistic properties of the terpenoids aromadendrene and 1,8-cineole from the essential oil of Eucalyptus globulus against antibiotic-susceptible and antibiotic-resistant pathogens. Phytomedicine 2010, 17, 1061–1066. [Google Scholar] [CrossRef] [PubMed]
  439. Bassolé, I.H.N.; Juliani, H.R. Essential oils in combination and their antimicrobial properties. Molecules 2012, 17, 3989–4006. [Google Scholar] [CrossRef] [PubMed]
  440. Ntalli, N.G.; Ferrari, F.; Giannakou, I.; Menkissoglu-Spiroudi, U. Synergistic and antagonistic interactions of terpenes against Meloidogyne incognita and the nematicidal activity of essential oils from seven plants indigenous to Greece. Pest Manag. Sci. 2011, 67, 341–351. [Google Scholar] [CrossRef] [PubMed]
  441. Wanghen, P.F.; Chang, S.T. Antifungal activities of essential oils and their constituents from indigenous cinnamon (Cinnamomum osmophloeum) leaves against wood decay fungi. Bioresource Technol. 2005, 96, 813–818. [Google Scholar]
  442. Larsen, A.G.; Knoechel, S. Antimicrobial activity of food-related Penicillium sp. against pathogenic bacteria in laboratory media and a cheese model system. J. Appl. Microbiol. 1997, 83, 111–119. [Google Scholar] [CrossRef] [PubMed]
  443. Jayaprakasha, G.K.; Rao, L.J.M. Chemistry, Biogenesis, and Biological Activities of Cinnamomum zeylanicum. Cr. Rev. Food Sci. 2011, 51, 547–562. [Google Scholar] [CrossRef] [PubMed]
  444. Bosca, F.; Miranda, M.A. Photosensitizing drugs containing the benzophenone chromophore. J. Photochem. Photobiol. B Biol. 1998, 43. [Google Scholar] [CrossRef]
  445. Ogunlesi, M.; Okiei, W.; Ofor, E.; Osibote, A.E. Analysis of the essential oil from the dried leaves of Euphorbia hirta Linn (Euphorbiaceae), a potential medication for asthma. Afr. J. Biotechnol. 2009, 8, 7042–7050. [Google Scholar]
  446. Zavala-Sanchez, M.A.; Perez-Gutierrez, S.; Perez-Gonzalez, C.; Sanchez-Saldivar, D.; Arias-Garcia, L. Antidiarrhoeal activity of nonanal, an aldehyde isolated from Artemisia ludoviciana. Pharm. Biol. 2002, 40, 263–268. [Google Scholar] [CrossRef]
  447. Kobaisy, M.; Tellez, M.R.; Webber, C.L.; Dayan, F.E.; Schrader, K.K.; Wedge, D.E. Phytotoxic and fungitoxic activities of the essential oil of kenaf (Hibiscus cannabinus L.) leaves and its composition. J. Agric. Food Chem. 2001, 49, 3768–3771. [Google Scholar] [CrossRef] [PubMed]
  448. Grundy, S.M.; Denke, M.A. Dietary influences on serum lipids and lipoproteins. J. Lipid Res. 1990, 31, 1149–1172. [Google Scholar] [PubMed]
  449. Dilika, F.; Bremner, P.D.; Meyer, J.J.M. Antibacterial activity of linoleic and oleic acids isolated from Helichrysum pedunculatum: A plant used during circumcision rites. Fitoterapia 2000, 71, 450–452. [Google Scholar] [CrossRef]
  450. Seidel, V.; Taylor, P.W. In vitro activity of extracts and constituents of Pelagonium against rapidly growing mycobacteria. Int. J. Antimicrob. Ag. 2004, 23, 613–619. [Google Scholar] [CrossRef] [PubMed]
  451. Anderson, I.B.; Mullen, W.H.; Meeker, J.E.; Khojasteh-Bakht, S.C.; Oishi, S.; Nelson, S.D.; Blanc, P.D. Pennyroyal toxicity: measurement of toxic metabolite levels in two cases and review of the literature. Ann. Intern. Med. 1996, 124, 726–734. [Google Scholar] [CrossRef] [PubMed]
  452. Woolf, A. Essential oil poisoning. J. Toxicol. Clin. Toxicol. 1999, 37, 721–727. [Google Scholar] [CrossRef] [PubMed]
  453. Gordon, W.P.; Forte, A.J.; McMurtry, R.J.; Gal, J.; Nelson, S.D. Hepatotoxicity and pulmonary toxicity of pennyroyal oil and its constituent terpenes in the mouse. Toxicol. Appl. Pharm. 1982, 65, 413–424. [Google Scholar] [CrossRef]
  454. Zhou, S.; Koh, H.L.; Gao, Y.; Gong, Z.Y.; Lee, E.J.D. Herbal bioactivation: The good, the bad and the ugly. Life Sci. 2004, 74, 935–968. [Google Scholar] [CrossRef] [PubMed]
Table
Table 1. Phenolic substances isolated from Kazakhstan Ziziphora species. (N.f.—not found).
Table 1. Phenolic substances isolated from Kazakhstan Ziziphora species. (N.f.—not found).
Flavonoids
Name of Compound and IDIsolation/Detection in Kazakhstan spp. of ZiziphoraBiological ActivityChemical Structure
Molecules 21 00826 i001
R1R2R3R4R5R6
Apigenin (1)Z. tenuior [38];
Z. clinopodioides [4,39,40]		Vasorelaxant activity (IC50 189.4 ± 12.4 µM) [39]; Some inhibitory activity on NO production stimulated by LPS and IFN-γ in RAW 264.7 cells [4]
Review on apigenin (1) on breast cancer [41]
Anticancer activity review [42,43,44]
Review on apigenin (1) impact on gastric cancer [45]
General review on the impact of apigenin (1) on health and disease [46]		HOHHHOHH
Chrysin (2)Z. clinopodioides [39]Vasorelaxant activity (IC50 347.8 ± 23.9 µM) [39]
Neuroprotective activity reviewed [47]
Anticancer activity reviewed [48,49]
Recent general review on bioactivities of chrysin (2) and its derivatives [50]		HOHHHHH
Luteolin (3)Z. clinopodioides [4]Some inhibitory activity on NO production stimulated by LPS and IFN-γ in RAW 264.7 cells [4]
Anticancer [51,52]
Review on anti-inflammatory and neuroprotective effect [53,54]
Neurotrophic effects [55]
Anti-allergic [56]
Anti-atherogenic [57]
Cardioprotective [58]
General reviews on luteolin (3) [59,60]		HOHHOHOHH
Thymonin (4)Z. clinopodioides [39,61]Low vasorelaxant activity (IC50 not calc.) [39]
Toxicity against Artemia salina larvae [62]
Antiradical [63]
Weak antibacterial effect [61]		OHOCH3OCH3OCH3OHH
Acacetin (5)Z. clinopodioides [39]Low vasorelaxant activity (IC50 not calc.) [39]
Inhibition of angiogenesis [64,65]
Induction of apoptosis in different cancer cell lines [66,67,68,69,70]
Inhibition of TNF-related apoptosis [71]
Anticancer [72,73]
Induction of melanogenesis in B16F10 cells [74]
Cytotoxic against HL-60 cells cells [75]
Interaction with telomeres [76]
Antimetastatic effect [77,78]		HOHHHOCH3H
Diosmetin (6)Z. clinopodioides [4]Some inhibitory activity on NO production stimulated by LPS and IFN-γ in RAW 264.7 cells [4]
Cytotoxic against HL-60 cells cells [75]
Induction of melanogenesis in B16F10 cells [73,74]
Review on bioactivity [79]		HOHHOHOCH3H
Diosmin (7)Z. clinopodioides [80]Antidiabetic activity (reviewed by Abdurrazak et al. [81])
Review on clinical use [82]		HO-Glc-RhaHOHOCH3Hf
Linarin (8)Z. clinopodioides [44,80]Inhibition of mucin production and secretion in airways epithelial cells [83]
Hepatoprotective [84]
Potential inhibitor of CDK4 in retinoblastoma [85]
Neuroprotective [86]
Inhibition of acetylcholinesterase [87]
Anti-inflammatory [88]; Anti-inflammatory in vivo [89]
Depressant effect on CNS [90,91]		HO-Glc-RhaHHOCH3H
Ziziphorin A (9)Z. tenuior [39]n.f.HOHHHOCO(CH2)17CH3H
Ziziphorin B (10)Z. tenuior [39]n.f.HOHHHHOCO(CH2)25CH3)
5,7,2′-trihydroxyflavone-2′-O-β-d-glucopyranoside (11)Z. clinopodioides [44]n.f.HOHHHHO-Glc
Other Phenolics
Name of Compound and IDIsolation/Detection in Kazakhstan spp. of ZiziphoraBiological ActivityChemical Structure
Molecules 21 00826 i002
Acetovanillone (syn. apocynin) (12)Z. clinopodioides [39]Low vasorelaxant activity (IC50 not calc.) [39]
Review on its potential in treatment of cardiovascular diseases [92]
Review on its potential in treatment of neurodegenerative diseases [93]		R1R2
OHOCH3
4-Hydroxyaceto-phenone (syn. piceol) (13)Z. clinopodioides [39]Low vasorelaxant activity (IC50 not calc.) [39]OHH
Acetophenone (14)Z. tenuior [94]Tyrosinase inhibition [95]
Acaricidal effect [96]		HH
Picein (15)Z. clinopodioides ([4,44]Weak inhibitory activity on NO production stimulated by LPS and IFN-γ in RAW 264.7 cells [4]
Glucosidase inhibitor (review by Benalla et al. [97])		O-GlcH
2-Methoxy-4-vinylphenol (16)Z. clinopodioides [15]n.f. Molecules 21 00826 i003
Caffeic acid (17)Z. clinopodioides [80]Anticancer potential reviewed [98]
Protection of endothelial cells (review by Fuentes and Palomo [99])
General review on applications [100]		 Molecules 21 00826 i004
Ethyl ester of caffeic acid (18)Z. clinopodioides [4]Weak inhibitory activity on NO production stimulated by LPS and IFN-γ in RAW 264.7 cells [4]
Antihypertensive [101,102]
Anti-inflammatory [103,104,105]
Antidiabetic [106]
Inhibitory activity against amyloidogenesis [107]
Antioxidative [108,109,110,111]
Anticancer [112]		 Molecules 21 00826 i005
Rosmarinic acid (19)Z. clinopodioides [80]Review on pharmaceutical and clinical usage [113]
Neuroprotective—review [114]
General review on applications [115]
Review on anticancer potential [116]		 Molecules 21 00826 i006
Salicylic acid (20)Z. clinopodioides [80]Effect on cardiovascular system reviewed [117]
Pharmacological importance reviewed [118]		 Molecules 21 00826 i007
Benzoic acid (21)Z. clinopodioides [4]Weak inhibitory activity on NO production stimulated by LPS and IFN-γ in RAW 264.7 cells [4]
Properties reviewed here [119]		 Molecules 21 00826 i008
(Z)-3-Hexen-1-ol benzoate (22)Z. tenuior [94]n.f. Molecules 21 00826 i009
Benzylalcohol glucoside (23)Z. clinopodioides [4]Weak inhibitory activity on NO production stimulated by LPS and IFN-γ in RAW 264.7 cells [4]
Antihypertensive effect [120]
Low anti-inflammatory activity [121]
Neuroprotective effect [122]
Weak inhibition of TPA-induced EBV-EA activation [123]		 Molecules 21 00826 i010
Phenethylalcohol glucoside (24)Z. clinopodioides [4]Weak inhibitory activity on NO production stimulated by LPS and IFN-γ in RAW 264.7 cells [4]
Neuroprotective effect [122]
Antiradical activity, weak ACE-inhibitory activity [124]
Inhibition of osteoclast differentiation [125]		 Molecules 21 00826 i011
Eugenol (25)Z. tenuior [94]Insecticidal (against L. serricorne) [126]
Acaricidal activity [127]
Antibacterial [128]
Inhibition of tyrosine kinase [129]
Review on possible antidepressive activity [130]
Review on antibacterial effect against cariogenic bacteria [131]
Review on possible synergy of eugenol containing essential oils and eugenol (25) with antibiotics [132]
Review on antioxidative effect [133]
General properties reviewed here [134]		 Molecules 21 00826 i012
Table
Table 2. Triterpenic substances isolated from Kazakhstan Ziziphora species. (N.f.—not found).
Table 2. Triterpenic substances isolated from Kazakhstan Ziziphora species. (N.f.—not found).
Triterpenes and Sterols
Name of Compound and IDIsolation/Detection in Kazakhstan spp. of ZiziphoraBiological ActivityChemical Structure
Oleanolic acid (26)Z. clinopodioides [4,80,143]Weak inhibitory activity on NO production stimulated by LPS and IFN-γ in RAW 264.7 cells [4]
Review on effect on vascular functions [140]
General review on bioactivity and mechanisms of effect [143,144]		 Molecules 21 00826 i013
Ursolic acid (27)Z. clinopodioides [4,80,143]Weak inhibitory activity on NO production stimulated by LPS and IFN-γ in RAW 264.7 cells [4]
Cytotoxicity against HL-60 and LLC cell line [145]
Recent general review on bioactivity [142]
General review on bioactivity [146]
Review on anticancer potential [147,148]		 Molecules 21 00826 i014
Maslinic acid (28)Z. clinopodioides [4]Weak inhibitory activity on NO production stimulated by LPS and IFN-γ in RAW 264.7 cells [4]
Cytotoxicity against HL-60 and LLC cell line [145]
Recent review on bioactivity [139,144]
Review on anti-inflammatory potential [149]		 Molecules 21 00826 i015
Daucosterol (29)Z. clinopodioides [44]Immunoregulatory effect [150]
Anti-inflammatory activity [151]; anti-inflammatory in ear edema assay [152]; topical anti-inflammatory activity in the mouse ear edema model [153]; weak 5-LOX inhibitory activity [154]
DPPH and ABTS; scavenging effect [155]; antioxidant [156]; inhibitory effect on nitric oxide production in LPS-activated RAW264.7 cells [157]
Antinociceptive [158]
Some anticomplementary activity [159]
Neuroprotective [160,161]; promotion of proliferation of neural stem cells [162]; Inhibition of acetylcholinesterase [163]
Inhibition of cancer cell proliferation [164], induction of apoptosis [165], antiproliferative [166], cytotoxic [167]; antiproliferative activity against HL-60, K562, HepG2 and CNE-1 cell lines [168] inhibition of MDA-MB-231 cancer cell migration [169]; Ability to activate PPARγ and PPARβ [170]
Inhibition of α-glucosidase [171]
Antibacterial effect against E. coli [172], against H. pylori and S. aureus [173]; against E. coli and S. aureus [174]; against Bacillus subtilis and S. aureus [175]
Inhibitory effect on reverse transcriptase [176]
Suppression of HCl/ethanol-induced gastric lesions [177]
Inhibitory activity against osteoclast differentiation by suppressing TRAP activity in RANKL-induced RAW 264.7 macrophage cells [178]		 Molecules 21 00826 i016
Table
Table 3. Mono and sesquiterpenic substances isolated from Kazakhstan Ziziphora species (N.f.—not found).
Table 3. Mono and sesquiterpenic substances isolated from Kazakhstan Ziziphora species (N.f.—not found).
Monoterpenes
Name of Compound and IDIsolation/Detection in Kazakhstan spp. of Ziziphora (Percentage Content when Given)Biological ActivityChemical Structure
Myrcene (syn. β-myrcene) (30)Z. clinopodioides (0.6%–1.9%) [9,15,185]Antibacterial, antitermitic, antifungal [187]
Antioxidant (DPPH) [188]
Some cytotoxic activity [189]
Low fumigant activity against various species of insects [190,191]
Sedative and motor relaxant effects in mice [192]
Anti-inflammatory activity in the mouse model of pleurisy induced by LPS [193]
Protective effect against t‑BOOH induced mutagenesis [194]
Immunomodulatory and protective effects against the immunotoxicity induced by TCDD in rats [195]; antioxidant activity against TCDD‑induced oxidative stress in rats liver [196]; neuroprotective after global cerebral ischemia/reperfusion-mediated oxidative and neuronal damage in mouse [197]
Gastroprotective effect against various ulcerogenic agents [198]
Analgesic activity reviewed [199]
Review on metabolism and toxicity [200]		 Molecules 21 00826 i017
Z. clinopodioides subsp. rigida (0.2%) [21]
Z. clinopodioides subsp. bungeana (0.3%) [201]
Z. tenuior (0.1%) [179,202]
(Z)-β-Ocimene (31)Z. clinopodioides (1.1%) [184]Antibacterial [187]
Antifungal (Candida strains, Cryptococcus neoformans, Epidermophyton floccosum, Microsporum canis and M. gypseum, Trychophyton mentagrophytes and T. verrucosum, Aspergillus flavus, A fumigatus, A. niger) [203,204]		 Molecules 21 00826 i018
Z. clinopodioides subsp. bungeana [201]
(E)-β-Ocimene (32)Z. clinopodioides (1.2%) [184]Antifungal (Candida strains, Cryptococcus neoformans, Epidermophyton floccosum, Microsporum canis and M. gypseum, Trychophyton mentagrophytes and T. verrucosum, Aspergillus flavus, A fumigatus, A. niger) [203,204] Molecules 21 00826 i019
3,7-Dimethyl-1,3,7-octa-triene (33)Z. tenuior [94]n.f. Molecules 21 00826 i020
α-Thujene (34)Z. clinopodioides (0.1%–1.2%) [15,184]n.f. Molecules 21 00826 i021
Z. clinopodioides subsp. rigida (0.1%) [21]
Z. clinopodioides subsp. bungeana [201]
Z. tenuior (0.48%) [94,179]
α-Phellandrene (35)Z. clinopodioides (0.3%) [184]Insecticidal activity against various species of insects [192,193]; larvicidal activity against various mosquito species [205,206]
Antinociceptive activity assessed in various chemical‑induced nociception models in rodents [207,208]
Antidepressant activity in rats [208]
Induction of autophagy in human liver tumour cells [209]; induction of necrosis [210]; induction of apoptosis in mice leukaemia WEHI‑3 cells in vitro [211]; promotion of the immune response by increasing the level of T‑cells, monocytes and macrophages in BALB/c mice in vivo [212]		 Molecules 21 00826 i022
α-Terpinene (36)Z. clinopodioides (2.0%) [184]Inhibition of P-glycoprotein-mediated transport of different substances [213]
Suppression of CNS in mice [214,215]
Some topical anti-inflammatory activity in carrageenan‑induced paw edema in rats [216]
Antioxidant activity in various free radical scavenging tests [217,218]
Antifungal activity tested against some food spoilage yeasts [219]
Larvicidal activity against mosquitoes Aedes aegypti and A. albopictus [206]
Antiviral activity against herpes simplex virus type 1 in vitro [220]
Review on some effects on cardiovascular system [221]
Trypanocidal activity against Trypanosoma evansi [222]		 Molecules 21 00826 i023
Z. clinopodioides subsp. rigida [21]
Z. clinopodioides subsp. bungeana (0.1%) [201]
Terpinolene (37)Z. clinopodioides (0.1%–0.2 %) [184]Inhibition of P-glycoprotein-mediated transport of different substances [213]
Anti-inflammatory (inhibition of NO production in LPS-stimulated RAW-264.7 macrophages) [223]
Inhibition of acetylcholinesterase and butyrylcholinesterase [224]
Suppression of CNS in mice [214,215,225]
Antiproliferative (tested on primary rat neurons and N2a neuroblastoma cells) [226]; antiproliferative effect on K562 cells [227]; some cytotoxic activity [190]		 Molecules 21 00826 i024
Z. clinopodioides subsp. rigida (0.5%) [21]
Z. clinopodioides subsp. bungeana (0.1%) [201]
Z. tenuior (0.19%) [94,179]
Insecticidal activity against Callosobruchus chinensis and Sitophilus oryzae [228]; larvicidal activity tested against various mosquito species [205,206,229]
Antioxidant activity in various free radical scavenging tests [217,218]; protective effect against LDL‑oxidation [230]
Review on some effects on cardiovascular system [221]
Antiviral activity against influenza A⁄PR⁄8 virus subtype H1N1 [231]
Limonene (38)Z. tenuior (0.51%–7.82%) [232]Insecticidal (against red imported fire ant) [233]
Fumigation activity against stored-product pest insects [234]
Anxiolytic effect in mice [225]
Gastroprotective in rats [235]
Pharmacological importance and properties reviewed [190,236,237]
Analgesic activity reviewed [199]
Review on some effects on cardiovascular system [221]
Review on metabolism and toxicity [200]		 Molecules 21 00826 i025
Z. clinopodioides [11,15]
p-Mentha-1(7,8)-diene (syn. pseudolimonene) (39)Z. tenuior (0.04%) [179]n.f. Molecules 21 00826 i026
p-Mentha-3,8-diene (40)Z. tenuior (1.65%) [179]n.f. Molecules 21 00826 i027
Z. clinopodioides subsp. bungeana [201]
4-Methyl-1-(1-methyl-ethenyl)-cyclohexene (syn. 3,8-p-menthadiene) (41)Z. tenuior [94]n.f. Molecules 21 00826 i028
3-Methyl-6-(1-methyl-ethylidene)-cyclohexene (syn. Isoterpinolene, 2,4-p-menthadiene) (42)Z. tenuior [94]n.f. Molecules 21 00826 i029
3-Isopropenyl-5,5-di-methyl-cyclopentene (43)Z. tenuior [94]n.f. Molecules 21 00826 i030
Menthone (44)Z. clinopodioides (6.2%–13.3%) [238]Antifungal effect against C. albicans, synergy with fluconazol [239]; antimicrobial activity against tested strains of bacteria, yeast and pathogenic fungi [240,241]
Insecticidal activity tested against various stored grain pests and vectors [242]; moderate insecticidal activity against Sitophilus zeamais [243]
Antidepressant-like effects in an unpredictable chronic mild stress mouse model of depression [244]		 Molecules 21 00826 i031
Piperitone (45)Z. clinopodioides (4.18%) [11]Repellent activity against ants of the genus Crematogaster [245]; insecticidal activity against larvae of Spodoptera littoralis [246] and against Callosobruchus maculatus [247]
Increase in antimicrobial activity of furazolidone and nitrofurantoin against bacteria of the family Enterobacteriaceae [248,249]
Fungicidal activity against Aspergillus flavus [250]		 Molecules 21 00826 i032
Z. clinopodioides subsp. rigida (1.4%) [21]
Z. clinopodioides subsp. bungeana (0.6%) [201]
Piperitenone (46)Z. clinopodioides (5.3%) [11]Antibacterial activity against 52 Gram-positive and Gram-negative bacterial species, disc diffusion method [11]
Insecticidal activity against Sitophilus zeamais [243]		 Molecules 21 00826 i033
Z. clinopodioides subsp. rigida (17.4%) [21]
p-Menth-4-en-3-one (47)Z. tenuior (0.5%) [202]n.f. Molecules 21 00826 i034
Piperitone oxide (48)Z. persica (0.32%) [251]Antibacterial activity against 19 Gram-positive and Gram-negative bacterial species [252] Molecules 21 00826 i035
Piperitenone oxide (49)Z. clinopodioides (0.16%) [11]Antimicrobial activity against strains of bacteria, yeast and pathogenic fungi [241,252]
Insecticidal activity against the West Nile virus mosquito Culex pipiens larvae [253] and against various stages of Anopheles stephensi [254]
Antinociceptive activity in acetic acid‑induced writhing test and in the second phase of formalin test [255]
Antiviral activity against herpes simplex virus type 1 [256]		 Molecules 21 00826 i036
Verbenone (50)Z. clinopodioides subsp. rigida (0.2%) [21]Antifungal activity against Botrytis cinerea [257]
Fumigation activity against stored-product pest insects [234]
Insecticidal activity against Acanthoscelides obtectus [258]		 Molecules 21 00826 i037
2-Acetyl-4,4-dimethyl-cyclopent-2-enone (51)Z. tenuior (2.49%) [94]n.f. Molecules 21 00826 i038
2-Isopropyl-5-methyl-3-cyclohexen-1-one (52)Z. tenuior [94], Z. tenuior (1.6%) [179]n.f. Molecules 21 00826 i039
Pulegone (53)Z. tenuior (86.29%–87.06%) [259]Insecticidal [260]
Fumigation activity against stored-product pest insects [234]
Anti-inflammatory activity reviewed [261]
Analgesic activity reviewed [199]
Review on metabolism and toxicity [200]		 Molecules 21 00826 i040
Z. clinopodioides (45.8%) [21]
3-Methyl-6-(1-methyl-ethenyl)-2-cyclohexen-1-one (syn. Isopiperitenone) (54)Z. tenuior (0.3%–1%) [94,259]n.f. Molecules 21 00826 i041
Carvotanacetone (55)Z. tenuior [94]Cytotoxic activity against MCF‑7 and Hep‑G2 cells [262]
Antifungal activity against tested phytopathogenic fungi [263]		 Molecules 21 00826 i042
Menthol (56)Z. clinopodioides (9.13%) [11]Antifungal effect against Candida albicans, synergy with fluconazol [239]
Fumigant activity [264]
Analgesic, antifungal, antibacterial, antipruritic, anticancer, anti-inflammatory, antitussive, antiviral, insecticidal activity reviewed in Kamatou et al. [265]
Gastroprotective effect in gastric ulcers induced by ethanol or indomethacin in Wistar male rats and also antidiarrheal and antiperistaltic effect; anti-apoptotic, antioxidant and anti-inflammatory activities [266,267]
Allosteric modulation of human α3β4 nicotinic acetylcholine receptors [268]
Analgesic activity reviewed [199]
Review on some effects on cardiovascular system [221]
Review on metabolism and toxicity [200]		 Molecules 21 00826 i043
Z. clinopodioides subsp. rigida (0.1%) [21]
Menthofuran (57)Z. tenuior (0.1%) [182]Acetyl and butyrylcholinesterase inhibitory activity [269] Molecules 21 00826 i044
Neomenthol (58)Z. clinopodioides subsp. rigida (2.1%) [21]Antibacterial activity against Escherichia coli [270]
Acaricidal activity against Tyrophagus putrescentiae [271]
Sedative in the pentobarbital‑induced sleep test in mice [272]		 Molecules 21 00826 i045
Z. clinopodioides subsp. bungeana [201]
Neo-iso-menthol (59)Z. clinopodioides subsp. bungeana (0.3%) [201]n.f. Molecules 21 00826 i046
Z. clinopodioides (0.12%–0.25%) [15]
Menthyl acetate (60)Z. clinopodioides (0.1%) [184]n.f. Molecules 21 00826 i047
Isomenthyl acetate (61)Z. clinopodioides subsp. rigida (0.5%) [21]n.f. Molecules 21 00826 i048
Thymol (62)Z. clinopodioides (0.17%–53.6%) [15,184]Antibacterial (Bacillus cereus, Micrococcus flavus, S. aureus, Listeria monocytogenes, E. coli, P. aeruginosa, Proteus mirabilis, Salmonella typhimurium) [261,273,274]
Antifungal (Trichophyton mentagrophytes, T. interdigitale, T. rubrum, T. erinaceum, T. soudanense, T. violaceum, Microsporum canis, M. gypseum, Epidermophyton flocosum, A. fumigatus, Scopulariopsis brevicaulis, Scytalidium dimidiatum, C. albicans, Cryptococcus neoformans, Malassezia pachydermatis [273]); against Botrytis cinerea [275]; against Penicillium funiculosum and P. ochrochloron, Aspergillus fumigatus, A. niger, A. flavus, A. ochraceus, C. albicans, Trichoderma viride) [187]; antifungal (Candida albicans, C. tropicalis, Saccharomyces cerevisiae, Cryptococcus neoformans, Microsporum gypseum, Trichophyton rubrum, T. mentagrophytes), antimicrobial (E. coli, P. aeruginosa, Yersinia enterocolitica, Salmonella enteritidis) activity [276]; antifungal (yeasts, dermatophyte and Aspergillus strains) [277]
Antifungal activity against various Candida strains and synergy with fluconazole [278]
Review on possible synergy of 62 containing essential oils and thymol (62) with antibiotics [132]
Antileshmanial (against L. chagasi) [279]
Antimalarial (P. falciparum) [280]
Low antinematocidal activity [281]
Antiviral (HSV-1) [282]
Cytotoxic (HeLa, B16, MCF-7, 3T3, MRC-5 cells) [283]; against P815 and PBMC [284]; induction of apoptosis [285]; cytotoxic effects on acute promyelotic cancer cell line HL‑60 [286]		 Molecules 21 00826 i049
Z. clinopodioides subsp. rigida (8%) [21]
Z. tenuior [94]
Anti-genotoxic (bleomycin-induced DNA damage) [287]
Anti-inflammatory activity in carrageenan-induced paw edema, MPO activity and peritonitis in rats [288]; anti-inflammatory activity in LPS‑stimulated mouse mammary epithelial cells via inhibition of the NF‑κB and MAPKs signalling pathways [289]; anti-inflammatory effect in ovoalbumin‑induced mouse asthma, possibly through inhibiting NF‑κB activation [290]; inhibition of S. aureus internalization into bovine mammary epithelial cells by inhibiting NF-κB activation [291]
Review on anti-inflammatory, antioxidant, and immunological effects [292]
Protective effect on radiation‑induced apoptosis in Chinese hamster lung fibroblast V79 cells [293]; DNA‑protective effects against H2O2-induced DNA lesions in human hepatoma HepG2 cells [294]; hepatoprotective effect against t‑BHP‑induced oxidative damage in Chang liver cells [84]; protective effect against cisplatin‑induced nephrotoxicity in rats [295]; protective effect against UVA‑ and UVB‑induced lipid peroxidation in NCTC 2544 cell line [296]; antioxidant [273,297,298,299]
Review on some effects on cardiovascular system [221]
Gastroprotective effects in the acute and chronic ulcer models in rats [300]
Positive allosteric modulator of the GABAA receptors in primary cultures of mouse cortical neurons [301]
Anti-hyperglycemic and anti-hyperlipidemic activity in high fat‑induced type 2 diabetic C57BL/6J mice [302] and protective effect in nephropathy [303]
Analgesic activity reviewed [199]
Review on metabolism and toxicity [200]; general review on thyme and 62 [304]
cis-Sabinene hydrate (63)Z. clinopodioides (0.3%–2.2%) [184]Antiviral (HSV-1) [282] Molecules 21 00826 i050
Z. clinopodioides subsp. bungeana [201]
trans-Sabinene hydrate (64)Z. clinopodioides subsp. rigida (0.1%) [21]Antiviral (HSV-1) [282]
Moderate repellent (against tick Amblyomma americanum) [305]		 Molecules 21 00826 i051
Z. tenuior [94]
p-Menth-3-en-8-ol (65)Z. clinopodioides (2.7%) [185]n.f. Molecules 21 00826 i052
Z. clinopodioides subsp. rigida (12.5%) [21]
Z. tenuior (53.97%) [179]
Linalool (66)Z. clinopodioides (1.8%–7.9%) [184]Antibacterial [128,187,306]
Antimycotic (Candida albicans) [307], against M. ramamnianus [308]
Repellent against mosquitoes [309]
Molluscicidal (against snail Oncomelania hupensis) and cercarcicidal (against Schistosoma japonicum) [310]
Anti-inflammatory (in carrageenan‑induced edema and inhibition of hyperalgesia induced by L‑glutamate and prostaglandin E2 in rats) [311]; anti-inflammatory (through inhibition of the expression of TNF-α and IL-6 in LPS-stimulated RAW 264.7 cells) [312]; anti-inflammatory (in cigarette smoke-induced ALI in mice through inhibiting NF‑κB activation) [313]
Cytotoxic (human amelanotic melanoma cell line C32, renal cell adenocarcinoma ACHN, hormone-dependent prostate carcinoma LNCaP) [314]; induction of apoptosis (variety of human leukaemia cells) [315,316,317]
Hypocholesterolemic (through inhibition of HMG-CoA reductase and conversion of lanosterol to cholesterol) [318,319]
Protective effect against t‑BOOH induced mutagenesis [194]
Review on some effects on cardiovascular system [221]
Sedative and anxiolytic [320]; antidepressant [321]; GABAA receptor modulation [322]
Analgesic activity reviewed [199]
Review on metabolism and toxicity [200]		 Molecules 21 00826 i053
Z. clinopodioides subsp. rigida [21]
Borneol (67)Z. clinopodioides (0.9%–1.2%) [184]Inhibition of nicotinic acetylcholine receptor [323]
DNA-protective effects against H2O2 in primary rat hepatocytes and testicular cells [324]
Anti-inflammatory in an ALI model in mice through inhibition of the NF-κB and MAPKs signalling pathways [325]; suppression of expression of IL‑1β and IL‑6 in TNBS‑induced colitis in mice [326]
Penetration enhancer [327]; increasing of the brain bioavailability of different drugs [328]
Antibacterial (multi-drug resistant E. coli) [329]
Antiviral (HSV-1) [282]		 Molecules 21 00826 i054
endo-Borneol (68)Z. tenuior (0.14%) [202]Vasorelaxant effect on rat thoracic aorta artery rings [330]
Positive modulation of the activation of GABAA receptors [331]
Potentiation of SeC-induced apoptosis in human hepatocellular carcinoma cells [332]
Prolonging anaesthesia time of propofol by inhibiting its glucuronidation [333]		 Molecules 21 00826 i055
Bornyl acetate (69)Z. clinopodioides (3.3%) [184]Antifungal (against Pyrenophora avenae) [334]
Insecticidal (against Callosobruchus chinensis and Sitophilus oryzae) [228]
Anti-inflammatory in an ALI model in mice [335] and in human chondrocytes [336]
Antiabortive in pregnant mice [337]
Cytotoxic ((Eca-109, HepG2, HT29, MDA-MB-231, PC-3, SGC7901, SW1990 and U2-OS) and a normal cell line (HL-7702) [338]		 Molecules 21 00826 i056
Terpinen-4-ol (70)Z. clinopodioides (0.36%–18.2%) [15,184]Sedative and anaesthetic (on silver catfish juveniles) [339]; depressant effect on the CNS and significant anticonvulsant activity probably due to interaction with GABA receptors [340,341]
Low inhibition of acetylcholinesterase and butyrylcholinesterase [224]
Relaxant effect on vascular smooth muscle [342]
Review on some effects on cardiovascular system [221]
Anticancer (melanoma) [343]; antiproliferative activity in two murine cancer cell lines through induction of necrosis and cell cycle arrest [344]; induction of apoptosis in human non-small cell lung cancer [345]; anti-tumoral activity in human melanoma cells by induction of caspase-dependent form of apoptosis [346]
Antiviral activity against influenza A⁄PR⁄8 virus subtype H1N1 [231]
Anti-inflammatory (inhibition of NO production in LPS-stimulated RAW-264.7 macrophages) [223]; anti-inflammatory [216]; anti-inflammatory activity in a murine model of oral candidiasis [347]; suppression of the production of TNFα, IL‑1β, IL‑8, IL‑10 and PGE2 by LPS‑activated monocytes [348]
Antibacterial against MRSA and CoNS [349]
Low antinematocidal activity [281]
Antimycotic (C. albicans) [307,350]
Insecticidal (against L. serricorne) [351]
Trypanocidal activity against Trypanosoma evansi [222]		 Molecules 21 00826 i057
Z. clinopodioides subsp. rigida (0.4%) [21]
Z. clinopodioides subsp. bungeana (0.6%) [201]
Z. tenuior (0.08%) [202]
α-Terpineol (71)Z. clinopodioides (0.3%–5.3%) [184]Antifungal [187,350,352], antimicrobial activity [306]
Antiviral activity against influenza A⁄PR⁄8 virus subtype H1N1 [231]
Enhancement of GABA modulation [353]
Anticancer (melanoma cells) [343]
Insecticidal (against L. serricorne) [351]
Inhibition of the acetic acid-induced writhing and formalin-induced nociception in mice [354]
Analgesic activity reviewed [199]
Review on metabolism and toxicity [200]		 Molecules 21 00826 i058
1,8-Cineol (72)Z. clinopodioides (5.4%–21.6%) [185]Antimicrobial activity (MDR resistant bacteria) [355]
Hypocholesterolemic (through inhibition of HMG‑CoA reductase and conversion of squalene to lanosterol [319]
Analgesic activity reviewed [199]
Review on some effects on cardiovascular system [221]
Review on metabolism and toxicity [200]		 Molecules 21 00826 i059
Carvacrol (73)Z. clinopodioides (8.7%) [184]; Z. clinopodioides (52.7%) [183]Antifungal (Penicillium funiculosum and P. ochrochloron, Aspergillus fumigatus, A. niger, A. flavus, A. ochraceus, C. albicans, T. viride) [187,273,277]
Antibacterial (B. cereus, M. flavus, S. aureus, L. monocytogenes, E. coli, P. aeruginosa, P. mirabilis, S. typhimurium) [273,274]; against B. cinerea [275]; active against food spoilage microorganisms [356,357,358]
Low antinematocidal activity [281]
Antileishmanial (against L. chagasi) [279]
Antiviral (HSV-1) [283]; antiviral activity on enteric viruses [359]
Review on synergic effect with antibiotics [132]
Cytotoxic (HeLa, B16, MCF-7, 3T3, MRC-5 cells) [284]; against P815 and PBMC [284]; antiproliferative effects on a human metastatic breast cancer cell line, MDA‑MB 231 [360]; induction of apoptosis in HL‑60 and Jurkat cells by mitochondria‑mediated pathway through the involvement of caspase‑3 [361]
Cytotoxic effect on the intestinal cell line Caco‑2 [362]; inhibition of growth of N‑ras oncogene transformed mouse myoblast cells [363]
DNA‑protective effects against H2O2-induced DNA lesions in human hepatoma HepG2 cells [295]; antioxidant [273,297,299]
Anti-inflammatory (inhibition of NO production in LPS-stimulated RAW-264.7 macrophages) [223]; anti-inflammatory effect by reducing the production of IL‑1β and prostanoids, possibly through the induction of IL‑10 release [364]
Anti-genotoxic [287]
Anxiolytic, GABAA receptor modulation [322,365]
Bronchodilatory effect in guinea pigs [366]
Antinociceptive activity in mice in the acetic acid-induced abdominal constriction, formalin and hot-plate tests [367]
Acetyl‑ and butyrylcholinesterase inhibitory activity [269,368]
Analgesic activity reviewed [199]
Review on anti-inflammatory, antioxidant, and immunological effects [292]
Review on some effects on cardiovascular system [221]
General reviews on 73 [369,370]		 Molecules 21 00826 i060
Z. tenuior [94]
2-Methyl-5-(1-methyl-ethyl)phenol acetate (syn. carvacryl acetate) (74)Z. tenuior [94]Anthelmintic Haemonchus contortus [371]
Anti-inflammatory effect through inhibition of edema induced by carrageenan, histamine, serotonin or PGE2 [372]
Anxiolytic-like effect probably through acting on the GABAergic system [373,374]		 Molecules 21 00826 i061
trans-p-Mentha-2,8-di-enol (syn. trans-Isopiperitenol) (75)Z. tenuior [94]n.f. Molecules 21 00826 i062
cis-Verbenol (76)Z. clinopodioides subsp. rigida (0.1%) [21]Antibacterial (multi-drug resistant E. coli) [329]
Insecticidal activity (against Lasioderma serricorne) [351]
GABAA receptor modulation [322]
Repellent activity against Anopheles gambiae [375]
Anti-ischemic and anti-inflammatory activity [376]		 Molecules 21 00826 i063
trans-Verbenol (77)Z. clinopodioides subsp. rigida (0.1%) [21]Antibacterial (multi-drug resistant E. coli) [329]
GABAA receptor modulation [322]		 Molecules 21 00826 i064
Cuminyl aldehyde (syn. cumaldehyde) (78)Z. clinopodioides subsp. rigida (0.8%) [21]Tyrosinase inhibitory activity [377]
Suppression of melanin formation in cultured murine B16‑F10 melanoma cells [378]		 Molecules 21 00826 i065
Z. clinopodioides (0.12%–0.24%) [15]
Ziziphoroside A (79)Z. clinopodioides [4]Weak inhibitory activity on NO production stimulated by LPS and IFN-γ in RAW 264.7 cells [4] Molecules 21 00826 i066
Ziziphoroside B (80)Z. clinopodioides [4]Weak inhibitory activity on NO production stimulated by LPS and IFN-γ in RAW 264.7 cells [4] Molecules 21 00826 i067
Ziziphoroside C (81)Z. clinopodioides [4]Weak inhibitory activity on NO production stimulated by LPS and IFN-γ in RAW 264.7 cells [4] Molecules 21 00826 i068
Schizonepetoside C (82)Z. clinopodioides [4]Weak inhibitory activity on NO production stimulated by LPS and IFN-γ in RAW 264.7 cells [4] Molecules 21 00826 i069
Schizonepetoside A (83)Z. clinopodioides [4]Some inhibitory activity on NO production stimulated by LPS and IFN-γ in RAW 264.7 cells [4] Molecules 21 00826 i070
9-O-Glucopyranosyl-p-menthan-3-one (84)Z. clinopodioides [4]Weak inhibitory activity on NO production stimulated by LPS and IFN-γ in RAW 264.7 cells [4] Molecules 21 00826 i071
4aα,7α,7aα-Nepeta-lactone (85)Z. tenuior (0.5%) [94,179]Some activity against Helicobacter pylori [379] and repellent activity against mosquitoes [380] Molecules 21 00826 i072
Sesquiterpenes
Name of Compound and IDIsolation/Detection in Kazakhstan spp. of Ziziphora (Percentage Content When Given)Biological ActivityChemical Structure
Germacrene B (86)Z. clinopodioides (1.1%) [11]n.f. Molecules 21 00826 i073
Germacrene D (87)Z. clinopodioides (0.24%–4.0 %) [15,184]Effective aphid repellent [381] Molecules 21 00826 i074
Z. clinopodioides subsp. rigida (1.1%) [21]
Z. tenuior (0.13%) [94,179]
Z. clinopodioides subsp. bungeana (0.3%) [201]
Bicyclogermacrene (88)Z. clinopodioides (0.6%) [185]Low antibacterial effect (S. aureus, B. cereus, A. baumanii, E. coli, P. aeruginosa) [382] Molecules 21 00826 i075
Z. clinopodioides subsp. bungeana (0.1%) [201]
β-Bisabolene (89)Z. clinopodioides (0.2%) [184]Synergistic antibacterial activity with ampicillin against strain of S. aureus [383] Molecules 21 00826 i076
Z. tenuior [94]
Caryophyllene oxide (β-caryophyllene oxide) (90)Z. clinopodioides (0.5%) [184]Antitermitic [187], antifungal [308,384], antimicrobial [385]
Analgesic and anti‑inflammatory activity in tested mice [386]
Modest cytotoxic activity against tested human tumor cell lines [387]
Anti-cancer effects through the modulation of the PI3K/AKT/mTOR/S6K1 and MAPK signalling [388]		 Molecules 21 00826 i077
Z. tenuior (0.11%–0.32%) [94,179,202]
Caryophyllene (syn. β-caryophyllene, trans-caryophyllene, (E)-caryophyllene) (91)Z. tenuior (0.22%) [94,179]Antifungal, antibacterial [187]
Antiprotozoal (T. cruzi, L. infantum) [389]
Fumigant against Lasioderma serricorne [390]
Antihyperglycemic effect by decreasing blood glucose and increasing plasma insulin in diabetic rats [391]
Antioxidant effect and inhibition of 5‑lipoxygenase in CCl4‑induced fibrosis in rats [392]
Anti-inflammatory effect through the inhibition of TNFα and PGE2 and it is also effective in reducing PAF‑, bradykinin‑, ovoalbumin‑induced mouse paw edema [393,394]
Low inhibition of acetylcholinesterase and butyrylcholinesterase [224]
Review on metabolism and toxicity [200]		 Molecules 21 00826 i078
α-Humulene (syn. α-Caryophyllene) (92)Z. clinopodioides (2.7%–4.5%) [184]Antibacterial activity against Propionibacterium acnes (MIC of 3.13 μg/mL) [395]
Antiproliferative activity against several cancer cell lines (MCF-7, PC-3, M4BEU, CT-26, human amelanotic melanoma cell line C32, renal cell adenocarcinoma ACHN, hormone-dependent prostate carcinoma LNCaP, A-549 and human colon adenocarcinoma cell line DLD-1) [396,397,398,399,400,401]
Anti-inflammatory effect through the inhibition of TNFα, IL‑1β and PGE2 and it is also effective in reducing PAF‑, bradykinin‑, ovoalbumin‑ and histamine‑induced mouse paw edema [393,394]		 Molecules 21 00826 i079
δ-Cadinene (93)Z. tenuior [94]Antimicrobial activity against Streptococcus pneumoniae strains resistant to β-lactamic antimicrobials (MIC of 31.25 μg/mL) [402]
Antibacterial activity against Propionibacterium acnes (MIC of 3.13 μg/mL) [395]
Antileishmanial effect against L. donovani [403]		 Molecules 21 00826 i080
τ-Cadinol (94)Z. tenuior [94]Weak antimite activity against Dermatophagoides pteronyssinus [404]
Good antifungal activity against brown rot fungi Laetiporus sulphureus and weak antifungal activity against white rot fungi Coriolus versicolor [405]
Anti-wood-decay fungal activity [274,406]		 Molecules 21 00826 i081
Patchouli alcohol (95)Z. clinopodioides (0.1%–1.04 %) [15]Anti-inflammatory activity through inhibition of over-expression of iNOS and IL-6 in LPS-stimulated RAW264.7 and TNF-α HT-29 cells [407,408]; anti-inflammatory effect in vivo in rats [409]
Gastroprotective [410]
Review on metabolism and toxicity [200]		 Molecules 21 00826 i082
(Z)-6,10-dimethyl-5,9-undecadien-2-one (syn. Z-geranylacetone, nerylacetone) (96)Z. tenuior [94]n.f. Molecules 21 00826 i083
Cyclohexane, 1-ethenyl-1-methyl-2-(1-methylethenyl)-4-(1-methylethylidene) (97)Z. tenuior [94]n.f. Molecules 21 00826 i084
Spathulenol (98)Z. tenuior [94]Antimicrobial activity against S. aureus and P. mirabilis [385] Molecules 21 00826 i085
Bicyclo[5.2.0]no-nane, 2-methylene-4,8,8-tri-methyl-4-vinyl (99)Z. tenuior [94]Antimicrobial, anti-inflammatory, antihyperlipidemic, antioxidant activities [411]
Repellent activity against Tribolium castaneum and Myzus persicae [412]		 Molecules 21 00826 i086
2-Methylene-6,8,8-trimethyl-tricyclo-[5.2.2.0(1,6)]undecan-3-ol (100)Z. tenuior [94]n.f. Molecules 21 00826 i087
Ar-turmerone (101)Z. tenuior [94]Significant repellent action against Sitophilus zeamais and toxic effect against Spodoptera frugiperda [413]; insecticidal activities against Nilaparvata lugens and Plutella xylostella [414]
Inhibition of platelet aggregation induced by collagen (IC50, 14.4. μM) and arachidonic acid (IC50, 43.6. μM) and no effect on PAF and thrombin-induced platelet aggregation on washed rabbit platelets [415]; anti-inflammatory effects through blocking of NF-κB, JNK and p38 MAPK signalling pathways in amyloid β-stimulated microglia [416]
Review on activity [417]		 Molecules 21 00826 i088
Table
Table 4. Miscellaneous substances isolated from Kazakhstan Ziziphora species (N.f.—not found).
Table 4. Miscellaneous substances isolated from Kazakhstan Ziziphora species (N.f.—not found).
Name of Compound and IDIsolation/Detection in Kazakhstan spp. of Ziziphora (Percentage Content When Given)Biological ActivityChemical Structure
Styrene (102)Z. tenuior [94]n.f. Molecules 21 00826 i089
Benzaldehyde (103)Z. tenuior [94]Weak antifungal activity against wood decay fungi [441]
Antimicrobial activity against Listeria monocytogenes and Salmonella typhimurium [442]		 Molecules 21 00826 i090
2-Methyl-3-methylbutyl-butanoic acid ester (104)Z. tenuior [94]n.f. Molecules 21 00826 i091
n-Amyl isovalerate (105)Z. tenuior [94]n.f. Molecules 21 00826 i092
3-Phenyl-2-propenal (syn. cinnamaldehyd) (106)Z. tenuior [94]Antibacterial, antifungal, antidiabetic, anti-inflammatory, antiproliferative activities ([132,443]
Inhibition of tyrosin kinase [129]		 Molecules 21 00826 i093
2,4,4,6-Tetramethyl-6-phenyl-1-heptene (107)Z. tenuior [94]n.f. Molecules 21 00826 i094
Benzophenone (108)Z. tenuior [94]Photosensitization of lipid peroxidation due to H-abstraction by its long lived triplet state [444] Molecules 21 00826 i095
6,10,14-Trimethyl-2-pentadecanone (109)Z. tenuior [94]Could be effective repellent against Anopheles species [445] Molecules 21 00826 i096
2,6,10,14-Tetramethyl-heptadecane (110)Z. tenuior [94]n.f. Molecules 21 00826 i097
1-octen-3-ol (111)Z. clinopodioides [238]n.f. Molecules 21 00826 i098
1-octen-3-yl acetate (112)Z. clinopodioides subsp. bungeana (Juz.) Rech.f. [201]n.f. Molecules 21 00826 i099
Nonadecane (113)Z. tenuior [94]n.f. Molecules 21 00826 i100
Heneicosane (114)Z. tenuior [94]n.f. Molecules 21 00826 i101
3-octanol (115)Z. clinopodioides (0.9%) [184]n.f. Molecules 21 00826 i102
Z. tenuior [94]
Nonanal (116)Z. tenuior [94]Significant inhibitory effect on mice with diarrhoea induced with castor oil, MgSO4 and arachidonic acid [446]
Low antifungal activity against fungi of the genus Colletotrichum [447]		 Molecules 21 00826 i103
n-Decanoic acid (syn. capric acid) (117)Z. tenuior [94]Increasing of total cholesterol level [448] Molecules 21 00826 i104
Dodecanoic acid (syn. lauric acid) (118)Z. tenuior [94]Increase in total cholesterol level [448] Molecules 21 00826 i105
Hexadecanoic acid (syn. palmitic acid) (119)Z. tenuior (0.13%–0.31%) [179,202]Increase in total cholesterol level [448] Molecules 21 00826 i106
Z. tenuior [94]
9,12-Octadecadienoic acid (syn. linoleic acid) (120)Z. tenuior (0.71%) [187]Reduction of LDL cholesterol [448]
Antibacterial activity against five Gram-positive bacteria [449] and significant activity against rapidly-growing mycobacteria [450]		 Molecules 21 00826 i107
9-Octadecenoic acid (syn. oleic acid) (121)Z. tenuior (0.89%) [202]High concentration may reduce LDL cholesterol [448]
Antibacterial activity against three of the five tested Gram-positive bacteria [449]		 Molecules 21 00826 i108
Erigeside B (122)Z. clinopodioides [4]Weak inhibitory activity on NO production stimulated by LPS and IFN-γ in RAW 264.7 cells [4] Molecules 21 00826 i109

Share and Cite

MDPI and ACS Style

Šmejkal, K.; Malaník, M.; Zhaparkulova, K.; Sakipova, Z.; Ibragimova, L.; Ibadullaeva, G.; Žemlička, M. Kazakh Ziziphora Species as Sources of Bioactive Substances. Molecules 2016, 21, 826. https://doi.org/10.3390/molecules21070826

AMA Style

Šmejkal K, Malaník M, Zhaparkulova K, Sakipova Z, Ibragimova L, Ibadullaeva G, Žemlička M. Kazakh Ziziphora Species as Sources of Bioactive Substances. Molecules. 2016; 21(7):826. https://doi.org/10.3390/molecules21070826

Chicago/Turabian Style

Šmejkal, Karel, Milan Malaník, Karlygash Zhaparkulova, Zuriyadda Sakipova, Liliya Ibragimova, Galya Ibadullaeva, and Milan Žemlička. 2016. "Kazakh Ziziphora Species as Sources of Bioactive Substances" Molecules 21, no. 7: 826. https://doi.org/10.3390/molecules21070826

APA Style

Šmejkal, K., Malaník, M., Zhaparkulova, K., Sakipova, Z., Ibragimova, L., Ibadullaeva, G., & Žemlička, M. (2016). Kazakh Ziziphora Species as Sources of Bioactive Substances. Molecules, 21(7), 826. https://doi.org/10.3390/molecules21070826

Article Metrics

Back to TopTop