Abstract
Pistacia, a genus of flowering plants from the family Anacardiaceae, contains about twenty species, among them five are more popular including P. vera, P. atlantica, P. terebinthus, P. khinjuk, and P. lentiscus. Different parts of these species have been used in traditional medicine for various purposes like tonic, aphrodisiac, antiseptic, antihypertensive and management of dental, gastrointestinal, liver, urinary tract, and respiratory tract disorders. Scientific findings also revealed the wide pharmacological activities from various parts of these species, such as antioxidant, antimicrobial, antiviral, anticholinesterase, anti-inflammatory, antinociceptive, antidiabetic, antitumor, antihyperlipidemic, antiatherosclerotic, and hepatoprotective activities and also their beneficial effects in gastrointestinal disorders. Various types of phytochemical constituents like terpenoids, phenolic compounds, fatty acids, and sterols have also been isolated and identified from different parts of Pistacia species. The present review summarizes comprehensive information concerning ethnomedicinal uses, phytochemistry, and pharmacological activities of the five mentioned Pistacia species.
1. Introduction
The genus Pistacia belongs to the Anacardiaceae, a cosmopolitan family that comprise about 70 genera and over 600 species. The species of the genus Pistacia are evergreen or deciduous resin-bearing shrubs and trees which are characterized as xerophytic trees and growing to 8–10 m tall. Pistacia lentiscus L., P. atlantica Desf., P. terebinthus L., P. vera L., and P. khinjuk Stocks. are distributed from the Mediterranean basin to central Asia [1, 2]. Three Pistacia species naturally occur in Iran: P. vera L., P. khinjuk Stocks., and P. atlantica Desf.; P. atlantica has three subspecies or varieties which have been described as cabulica, kurdica, and mutica [3]. P. vera is the only species of the genus cultivated commercially, and the rest of the species are mostly used as rootstocks for P. vera [1, 2].
Different parts of Pistacia species have been investigated for various pharmacological activities. Most of the papers are devoted to the resin of P. lentiscus that is known as mastic. In addition to their therapeutic effects, Pistacia species are used in food industry, for example, consumption of pistachio (P. vera) nut as food additive [4], P. terebinthus fruit as snack food or in making coffee-like drink [5, 6], and the anthocyanin composition of P. lentiscus fruit as food colorants [7].
Chemical studies on Pistacia genus have led to discovering diverse secondary metabolites in addition to high level of vitamins and minerals.
Our review presents a comprehensive report on phytochemical aspects, pharmacological activities, and toxicity of the genus Pistacia by focusing on the data reported since the year 2000 via papers on databases including PubMed, Scopus, Google Scholar, and Web of Science.
2. Traditional Uses
Traditional uses, plant part used, and pharmacological activities of Pistacia lentiscus, P. atlantica, P. terebinthus, P. vera, and P. khinjuk from different regions are listed in Table 1.
Different parts of Pistacia species including resin, leave, fruit, and aerial part have been traditionally used for a wide range of purposes. Among them, P. lentiscus is the most commonly used in different regions and resin of that has been utilized for as long as 5000 years. Resin of P. lentiscus has been used for variety of gastric ailments in the Mediterranean and Middle East countries for the last 3000 years [8]. It was used in ancient Egypt as incense; it has also been used as a preservative and breath sweetener [4] Most of the traditional uses reports for resin of P. atlantica are from Iran and have been used for the treatment of digestive, hepatic, and kidney diseases [9]. Fruit of P. vera (pistachio) is used all over the world. Records of the consumption of pistachio as a food date to 7000 BC [4]. Pistachio is cultivated in the Middle East, United States, and Mediterranean countries. Iran is one of the biggest producers and exporters of pistachio nuts [10]. In traditional Iranian medicine (TIM), different parts of P. vera, P. atlantica, P. khinjuk P. terebinthus, and P. lentiscus have been used for a long time as useful remedies for different diseases, for example, the fruit kernel of P. vera as a cardiac, stomach, hepatic, and brain tonic; the fruits of P. atlantica, P. khinjuk, and P. terebinthus for their aphrodisiac activity and treatment of liver, kidney, heart, and respiratory system disorders, and the gum resin of P. lentiscus, P. atlantica, P. khinjuk, and P. terebinthus for their wound healing activity, and treatment of brain and gastrointestinal disorders [9, 11].
3. Phytochemical Studies
Various compounds from different phytochemical groups were identified in Pistacia species. These are summarized below and also in Table 2 based on the structure of finding components.
3.1. Terpenoids
3.1.1. Monoterpenoids, Sesquiterpenoids, and Volatile Oil
Essential oil is one of the main components reported from different parts of Pistacia species including leaves, resin, ripe and unripe fruits, galls, leaf-buds, twigs, and flowers. Analysis of essential oils is mostly performed by means of gas-chromatography (GC) based techniques. There are many qualitative and quantitative variations between the content of essential oils. These variations are related to several parameters like plant species and part, sex of cultivars, harvesting time, geographical origin, and climatic conditions [12, 13]. Hydrocarbon and oxygenated monoterpens are the major chemical constituents in essential oil and among hydrocarbon monoterpens, α-pinene (1) has been reported as the main compound of some samples like P. vera [12, 14, 15], P. terebinthus [16–18], P. lentiscus [19–24], and P. atlantica [25–27]. In addition to α-pinene, other major components isolated from different parts of Pistacia species are as follows: limonene (2), α-terpinolene, and ocimene (3,4) from fruits and leaves of P. vera [28]; (E)-β-Ocimene (5) and limonene in fruits [18, 28, 29]; (E)-β-Ocimene and terpinen-4-ol (6) in leaves and p-cymen, (7) in young shoots of P. terebinthus [28–30]; bornyl acetate (8), terpinen-4-ol, sabinene (9), and myrcene (10) in fruits, terpinen-4-ol, myrcene, p-mentha-1 (7),8 diene (11), and ocimene from leaves [27, 28, 31], sabinene and p-mentha-1 (7),8 diene in leaf buds, and -carene (12) in unripe galls of P. atlantica [31, 32]. Monoterpens are also detected in mastic water which was separated from the mastic oil during steam distillation. Verbenone (13), α-terpineol (14), linalool (15), and trans-pinocarveol (16) are the main constituents of mastic water [33]. β-pinene (17) in oleoresin, β-myrcene and sabinene in fruits [28, 30, 34], terpinen-4-ol in aerial parts [22], and limonene, myrcene, sabinene, and teroinen-4-ol in leaves of P. lentiscus were determined as the main composition [28, 30, 35, 36].
Some of the other monoterpenes identified as effective antibacterial components of these essential oils are camphene (18), limonene, and carvacrol (19) from P. vera resin [12].
Sesquiterpenes isolated in lower amount compared with monoterpenes. Germacrene-D (20) and β-caryophyllene (21) were identified in P. lentiscus and P. terebinthus leaves with higher concentration in comparison with other sesquiterpenes [28]. Spathulenol (22), an azulenic sesquiterpene alcohol, is the predominant component of leaves of P. atlantica and P. khinjuk [37, 38]. Congiu et. al. [34] recovered Caryophyllene with the highest amount from P. lentiscus leaves by means of supercritical CO2 extraction. Germacrene-D in P. terebinthus flowers, β-caryophyllene in P. lentiscus galls, and Longifolene (23) in aerial parts of P. lentiscus are dominant [24, 29, 39].
3.1.2. Diterpenoids
Trace amounts of Diterpenoids were isolated from the essential oil of these species. Abietadiene (24) and abietatriene (25) were detected in essential oil of P. vera resin [12].
3.1.3. Triterpenoids
Resin of these species has been characterized by penta and tetracyclic triterpenes. Triterpenes such as masticadienonic acid (26), masticadienolic acid (27), morolic acid (28), oleanolic acid (29), ursonic acid (30) and their derivatives have been detected in acidic fractions of P. lentiscus, P. terebinthus, and P. atlantica resins [40–42]. Several triterpenoid compounds were isolated from neutral fraction of P. lentiscus and P. terebinthus resins like tirucallol (31), dammaradienone (32), β-Amyrin (33), lupeol (34), oleanolic aldehyde, and 28-norolean-12-en-3-one. Quantitative and qualitative varieties in chemical composition of resins according to the method of collection were reported [40, 41].
Anti-inflammatory properties have been reported from masticadienolic acid, masticadienonic acid, and morolic acid isolated from P. terebinthus [43]. Among triterpenes isolated from the resin of three sub-species of P. atlantica (kurdica, cabulica and mutica), 3-O-acetyl-3-epiisomasticadienolic acid (35) has been identified as the most effective antimicrobial agent [42].
3.2. Phenolic Compounds
Gallic acid (36), catechin (37), epicatechin (38), and gallic acid methyl ester were identified in P. vera seed and skin, leaves of P. lentiscus and leaves and galls of P. atlantica [44–46]. Bhouri et al. [47] demonstrated that digallic acid (39) from fruits of P. lentiscus has anti-mutagenic properties. Monounsaturated, diunsaturated, and saturated cardanols have been detected in P. vera kernel. 3-(8-Pentadecenyl)-phenol (40) was the dominating cardanol in P. vera [48]. Trans and cis isomers of phytoalexin, resveratrol (3,5,4′-trihydroxystilbene) (41-42), and trans-resveratrol-3-O-β-glucoside (trans-piceid) were quantified in P. vera kernel [49–51]. P. lentiscus leaf is a rich source of polyphenol compounds (7/5% of leaf dry weight) especially galloyl derivatives like mono, di, and tri-O-galloyl quinic acid (43) and monogalloyl glucose (44) [45].
1,2,3,4,6-Pentagalloyl glucose (45) and gallic acid from fruits of P. lentiscus were introduced as antioxidant and anti-mutagenic compounds [52].
Flavonoid compounds have been detected in different parts of these species. Naringenin (46), eriodyctyol (47), daizein (48), genistein (49), quercetin (50), kaempferol (51), apigenin (52), and luteolin (53) were isolated from P. vera fruit, and quercetin-3-O-rutinoside (54) is the main constituent of seed [44]. Decrease in flavonoid content of P. vera has been reported during the fruit ripening [51]. In addition to some known flavonoids isolated from P. terebinthus and P. atlantica fruits, 6′-hydroxyhypolaetin 3′-methyl ether (55) has been identified in fruits of P. terebinthus [46, 53]. Flavonoids were also isolated from aerial parts of P. atlantica and P. lentiscus, and quercetin-3-glucoside (56) was reported as the most abundant one [54]. 3-Methoxycarpachromene (57), a flavone with antiplasmodial activity, was isolated from aerial parts of P. atlantica [55].
Myricetin-3-glucoside (58), myricetin-3-galactoside (59), and myricetin-3-rutinoside (60) are the major flavonoid glycosides from P. khinjuk [54]. Myricetin derivatives also were determined as 20% of the total polyphenol amount of P. lentiscus leaves [45].
Anthocyanins have been reported from some Pistacia species. Cyanidin-3-O-glucoside (61), cyanidin-3-galactoside (62), and quercetin-3-O-rutinoside are the main anthocyanins of P. vera fruit [44, 56, 57]. Cyanidin-3-O-glucoside and delphinidin-3-O-glucoside (63) have been detected in P. lentiscus berries and leaves [7, 45].
3.3. Fatty Acids and Sterols
Pistacia species have oleaginous fruits considered by several researchers. The oil content in P. vera kernel and seed is about 50–60% [58, 59] and in ripe fruits of P. lentiscus, P. terebinthus, and P. atlantica is 32.8–45% [60–63]. The main fatty acid in seed and kernel of P. vera is oleic acid [58, 64, 65]. Oleic acid has been also determined as the most abundant fatty acid in oil of P. atlantica and P. terebinthus fruits [62, 66, 67]. Increase of oleic acid and decrease of linoleic acid have been recorded during ripening of P. lentiscus fruits [60]. Other fatty acids identified in these species are linolenic, palmitic, palmitoleic, stearic, myristic, eicosanoic, behenic, lignoceric, arachidonic, pentadecanoic, hexadecanoic, octadecanoic, and margaric acid [58, 66, 68].
The most abundant sterol reported in fruits of P. vera, P. atlantica, P. lentiscus, and P. terebinthus is β-sitosterol fallowed by campesterol, -avenasterol, stigmasterol, brassicasterol, and cholesterol [59, 60, 69, 70].
The oil from fruits of P. atlantica, P. lentiscus, and P. terebinthus, in addition to its desirable odor and taste, has been recommended as a new source for production of vegetable oils concerning the high amount of mono-unsaturated and omega-3 fatty acids like oleic acid and linolenic acid and high quantity of phytosterols like β-sitosterol [60, 68].
3.4. Miscellaneous
Chlorophylls a and b and lutein are the major colored components of P. vera nuts [56]. Pheophytin, β-carotene, neoxanthin, luteoxanthin, and violaxanthin were also determined in different samples of P. vera nuts [71]. α-tocopherol was determined in leaves of P. lentiscus, P. lentiscus var. chia, and P. terebithus [72]. Tocopherols and tocotrienols are the most abundant constituents of unsaponifiable matter of P. atlantica hull oil [73]. Different isomers of tocopherol, tocotrienol, and plastochromanol-8 have been identified in seed oil of P. terebinthus [70]. Evaluating the nutritional composition of P. terebinthus fruits illustrates the richness of this fruit in protein, oil, minerals, and fiber [62, 68].
4. Pharmacological Aspects
Different pharmacological activities of five mentioned Pistacia species have been described in detail in Table 3.
4.1. Antioxidant Activity
Different parts and constituents from P. lentiscus have been shown in vitro radical scavenging properties [23, 47, 52, 74–76]. Pistacia lentiscus var. chia and P. terebinthus var. chia resins were effective in protecting human LDL from oxidation in vitro [77]. P. atlantica leaf and fruit have shown antioxidant activity similar to or significantly higher than those of standard antioxidant compounds in different in vitro antioxidant assays [78–80]. However, the essential oil from P. atlantica leaf showed weak antioxidant activity in DPPH test compared to synthetic antioxidants [32]. P. vera fruit revealed significant antioxidant activity similar to the synthetic antioxidant [81]. Lipophilic extract from P. vera nuts showed lower antioxidant potential that than of hydrophilic extract [82]. One survey showed P. vera skins had a better antioxidant activity compared to seeds by means of four different assays because of higher content of antioxidant phenolic compounds in skins [44]. Antioxidant activity has been also reported from other parts of P. vera [83].
In one study, the extract from P. terebinthus leaf had nearly 12-fold higher antioxidant capacity than those of BHA and ascorbic acid [84]. P. terebinthus fruits showed noticeable metal-chelation properties as compared to EDTA and high radical scavenging activity similar to the standards. Antioxidant activity of the fruits may be elevated by roasting process [85].
4.2. Antimutagenic Activity
Essential oil and different extracts from P. lentiscus leaves indicated significant inhibitory effect on mutagenicity in vitro [86, 87]. Gallic acid, digallic acid, and 1,2,3,4,6-pentagalloylglucose, polyphenols isolated from the fruits of P. lentiscus, induced an inhibitory activity against mutagenicity and genotoxicity in in vitro assays [47, 52].
4.3. Antimicrobial and Antiviral Activities
Pistacia species have demonstrated significant antibacterial activity against various Gram positive and Gram negative bacteria as shown in Table 3. Antimicrobial activity of Pistacia lentiscus resin, the essential oil and gum from P. atlantica var. kurdica and its major constituent α-pinene and P. vera gum against Helicobacter pylori were recorded [15, 33]. A study indicated that antibacterial activity of P. lentiscus gum oil can be attributed to combination of several components rather than to one particular compound. Verbenone, R-terpineol, and linalool showed high antibacterial activity against Escherichia coli, Staphylococcus aureus, and Bacillus subtilis which is comparable to that of mastic oil itself [19]. P. lentiscus gum revealed selective antibacterial activity against Porphyromonas gingivalis and Prevotella melaninogenica and had antiplaque activity on teeth by inhibiting bacterial growth in saliva [76].
Significant antifungal activity was seen from essential oil of P. lentiscus leaf and gum, different extracts of P. khinjuk leaf, and essential oil of P. vera gum [15, 19, 38, 88]. Evaluating the effect of P. vera gum essential oil on growth of 13 bacteria and 3 yeasts demonstrated inhibitory effect on all of them except Bacillus cereus, Pseudomonas aeruginosa, and Klebsiella pneumonia and more effective yeasticide than nystatin. Carvacrol was found to be the most effective constituent [12, 15]. Lipophylic extracts from different parts of P. vera showed a little antibacterial activity and noticeable antifungal one against C. albicans and C. parapsilosis. Kernel and seed extracts showed significant antiviral activity [89].
Some active constituents of essential oil from the aerial parts of P. khinjuk responsible for its antibacterial and antifungal activity are α-pinene, β-pinene, myrcene, beta-caryophyllene, Germacrene B, and Spathulenol [38].
Organic fraction of mastic water obtained during the steam distillation of resin from Pistacia lentiscus var. chia indicated acceptable antifungal activity but moderate antibacterial effect. Among some of its major compounds, (±)-linalool and α-terpineol had the highest antimicrobial effect [33].
Essential oil from leaf and gum of P. atlantica showed acceptable antibacterial and antifungal activities [90–92]. However, leaf ethanolic extract had no distinct antimicrobial activity [88].
A remarkable inhibitory activity of different extracts and essential oil from P. lentiscus leaves was observed against Salmonella typhimurium; additionally, essential oil showed significant inhibitory effects against S. enteritidis and Staphylococcus aureus [86, 87].
As reported by Adams et al. [55], the leaves and twigs of P. atlantica and its active substance 3-methoxycarpachromene showed antiprotozoal activity against Plasmodium falciparum. P. atlantica var. kurdica gum controlled cutaneous leishmaniasis in mice infected with Leishmania major [93]. Extract from P. vera branch had significant inhibitory activity against Leishmania donovani and leaf extract inhibited Plasmodium falciparum without cytotoxicity on mammalian cells [94].
4.4. Anti-Inflammatory and Antinociceptive Activity
Anti-inflammatory and antinociceptive activity of five mentioned Pistacia species have been shown in Table 3.
P. terebinthus gall showed anti-inflammatory activity in different in vivo models of acute and chronic inflammation [95]. Masticadienonic acid (26), masticadienolic acid (27), and morolic acid (28), three triterpene isolated from P. terebinthus gall, seem to be responsible for its anti-inflammatory activity [43]. Additionally, oleanonic acid (29) from the galls of P. terebinthus, reduced the production of leukotriene B4 from rat peritoneal leukocytes and showed antiedematous activity in mice [96]. Oleoresin and leaf extract from P. vera showed significant anti-inflammatory and antinociceptive activity [97].
Extract of the resin of P. lentiscus var. Chia and its isolated phytosterol tirucallol (31) showed anti-inflammatory activity on human aortic endothelial cells and had significant inhibitory activity on adhesion molecules expression in TNF-α-stimulated human aortic endothelial cells [98]. It was proposed that the anti-inflammatory effect of P. lentiscus var. chia gum may be related to inhibition of protein kinase C which leads to decrease in superoxide and H2O2 production by NADPH oxidase [99].
4.5. Effects on Gastrointestinal Disorders
One of the most important traditional uses of gums from Pistacia species is for management of gastrointestinal disorders. Moreover, there are several scientific studies that confirm this property [100–102]. Resin of P. lentiscus significantly reduced the intensity of gastric mucosal damage induced by pyloric ligation, aspirin, phenylbutazone, reserpine, and restraint with cold stress via its antisecretory and cytoprotective activities [103]. In one double-blind placebo controlled trial, P. lentiscus gum improved the feeling of symptoms significantly in patients with functional dyspepsia [104]. Moreover, Pistacia species exerted significant antibacterial activity on Helicobacter pylori [15, 33]. Supplementation with P. lentiscus oil in experimental model of colitis delayed the onset and progression of acute colitis and led to decrease weight loss caused by the disease [105]. A polyherbal formula that contains P. lentiscus gum caused significant decrease in colonic damage and biochemical markers related to pathophysiology of IBS in rat model of colitis [106]. Adminstration of P. lentiscus var. chia resin to patients with established mild to moderate active crohn’s disease (CD) for 4 weeks caused significant reduction in CD activity index and plasma inflammatory mediators without any side effects and also as an immunomodulator resulted in significantly reduction in tumor necrosis factor-alpha (TNF-α) and enhanced macrophage migration inhibitory factor in these patients [107, 108].
4.6. Antidiabetic Activity
Aqueous leaf extract from P. atlantica showed significant inhibitory effect on α-amylase and α-glucosidase in vitro [109, 110]. It demonstrated significant acute postprandial antihyperglycemic activity comparable to metformin and glipizide in starch-fed rats. It also improved glucose intolerance [110]. However, another study on this extract did not show significant hypoglycemic activity when tested in normoglycemic and streptozocin-induced hyperglycemic rats [109]. Administration of P. lentiscus var. chia gum to human subjects for 12 months caused significantly decrease in serum glucose level among male subjects. Serum glucose in women was not affected [111].
4.7. Antitumor Activity
Among mentioned species of Pistacia, P. lentiscus is the most investigated for antitumor activity (Table 3). P. lentiscus var. chia gum inhibited proliferation and induced apoptosis of human colorectal tumor cells in vitro [112]. The resin exerted the most cytotoxic effect against promyelocytic leukemia among 13 human cell types and also inhibited the natural apoptosis of oral polymorphonuclear leukocytes [76]. The gum demonstrated anticancer activity via delaying the growth of colorectal tumors developed from human colon cancer cells xenografted into mice [8]. It also increased maspin (a mammary serine protease inhibitor with tumor suppressive activity for prostate cancers) expression in responsive prostate cancer cells and inhibited cell proliferation and blocked the cell cycle progression [113, 114]. Essential oil of P. lentiscus demonstrated significant inhibition on tumor growth in immunocompetent mice without signs of toxicity, related to apoptosis induction, reduced neovascularization, and inhibiting chemokine expression [115]. In addition, it had antiproliferative and proapoptotic effect on human leukemia cells and inhibited the release of vascular endothelial growth factor from these cells [116]. Despite many reports on antitumor activities of P. lentiscus, one in vivo study showed that the high dose of P. lentiscus gum promoted the preneoplastic lesions development in rat liver with increasing liver relative weight which proposed that desirable anticarcinogenic effects of mastic could be obtained at relatively low doses [117]. In one recent study, the current data on the anticancer activities of gum, oil, and extracts of P. lentiscus L. and its major constituent, have been reviewed comprehensively with special attention to the probable anticancer mechanisms [118].
The fruit extract of P. atlantica sub. kurdica showed growth inhibition in human colon carcinoma cells similar to Doxorubicin [119]. P. vera oleoresin demonstrated moderate cytotoxic effect against breast cancer cell line, hepatocellular carcinoma cell line, cervix cancer cell line, and normal melanocytes [120].
4.8. Effects on Liver and Serum Biochemical Parameters
P. lentiscus leaf demonstrated significant hepatoprotective activity against carbon tetrachloride induced hepatotoxicity in rats by reducing the level of bilirubin and activity of liver enzymes [121]. However, another study reported hepatic fibrosis, mild cholestasis, and depletion of reduced glutathione by long-term administration of aqueous leaf extract in healthy rats [122]. Administration of P. lentiscus var. chia gum for 18 months in healthy volunteers caused reduction in liver enzymes and exerted hypolipidemic effect [111]. Extracts from P. vera fruits have shown beneficial effects on HDL and LDL level in rabbit model of atherosclerosis [123]. Positive changes in lipid profile were recorded after three-week use of P. vera nuts in patients with moderate hypercholesterolemia. The decrease in triglyceride and LDL levels was not significant [124]. P. terebinthus fruit demonstrated hypolipidemic effect in hypercholesterolemic rabbits [125].
4.9. Effects on Atherosclerosis
More over than the antihyperlipidemic activity that described above, Pistacia species exerts their antiathesclerotic effects by direct activity on atherosclerotic lesions moreover than their antihyperlipidemic activity. Both methanolic and cyclohexane extracts from P. vera fruits have shown beneficial effects on HDL, LDL, and aortic intimal thickness in rabbit model of atherosclerosis. The methanolic extract additionally showed an antioxidant activity and remarkable decrease in aortic surface lesions [123]. P. terebinthus fruits inhibited the development of the atherosclerotic lesions in the thoracic artery [125]. P. lentiscus resin that downregulated CD36 mRNA expression (as the oxLDL receptor in macrophages that play a pivotal role in atherosclerotic foam cell formation) resulted in antiatherogenic effects [126].
4.10. Anticholinesterase Activity
Aqueous extracts from P. atlantica and P. lentiscus leaves showed strong acetylcholinesterase (AChE) inhibition [13]; additionally, both the methanol and ethyl acetate extracts of P. atlantica leaf showed relatively weak AchE inhibitory activity [127]. However, one study showed that ethyl acetate and methanol extracts of various commercially terebinth coffee brands (an oily brown-coloured powder produced from the dried and roasted fruits of P. terebinthus) and the unprocessed fruits of P. terebinthus did not have inhibitory activity against AChE and tyrosinase, while they selectively inhibited butyrylcholinesterase (BChE) at moderate levels [85].
5. Conclusion
In traditional Iranian medicine textbooks and papers, five species of Pistacia genus including P. vera, P. lentiscus, P. terebinthus, P. atlantica, and P. khinjuk had been introduced for treating the wide range of ailments. These species until now have been utilized in Iran by people for different nutritional and medicinal proposes. This review considered findings about phytochemical and pharmacological properties of these five species and presents comprehensive analysis of papers published since the year 2000. Ethnopharmacological data about these species may help us to know that many pharmacological aspects proposed nowadays for these species have been derived from traditional uses like antiseptic and antimicrobial, anti-inflammatory and anti-nociceptive, antihepatotoxic, and anticancer activities and their beneficial effects in gastrointestinal disorders. Furthermore, there are several pharmacological activities discussed in traditional medicine such as diuretic, lithontripic, anti-tussive, antirheumatic, antiasthmatic, antihypertensive, and aphrodisiac activities which are not supported by any current scientific documents, and so, they could be considered for investigation by researchers.
Phytochemical studies provided evidence for traditional applications of these species. With respect to phytochemical assays, triterpenes found in the resin and monoterpens are the most abundant composition of the essential oil from different parts of these species. Essential oil constituents might be valuable chemotaxonomic marker to ascertain different Pistacia chemotypes. Considering the therapeutic effect of isolated components, it can be concluded that terpenoids including mono, di-, and triterpenoids are associated with anti-inflammatory and antimicrobial effects. High amount of natural phenols and flavonoids is related to potent antioxidant and anticancer activities.
Review on current researches about the genus Pistacia L. highlighting pharmacological studies on crude plant parts, extracts, and some pure metabolites has provided scientific evidence for traditional uses and has revealed this genus to be a valuable source for medicinally important molecules.
So many studies were carried out on antioxidant activity of this genus considering their flavonoids, anthocyanins, and other phenolic compounds as preventive factors against cancer and cardiovascular diseases. P. lentiscus is the most studied species for antioxidant effects followed by P. atlantica, P. vera, P. terebinthus and P. khinjuk.
Most of the studies showed antimicrobial activity of these species especially P. lentiscus on a wide range of microorganisms including Gram-positive and -negative, aerobic and aerobic bacteria, viruses and fungi. The findings indicated that α-pinene, verbenone, R-terpineol, linalool, carvacrol and flavones are major compounds related to antibacrial activity.
Abbreviations
| ABTS: | 2,2′-Azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) |
| ALP: | Alkalin ephosphatase |
| ALT: | Alanine aminotransferase |
| AST: | Aspartate aminotransferase |
| B(a)p: | Benzo(a)pyrene |
| BHA: | Butylated hydroxyanisole |
| BHT: | Butylated hydroxytoluene |
| DMPD: | N,N-dimethyl-p-phenylendiamine |
| DPPH: | 2,2-Diphenyl-1-picrylhydrazyl |
| EC50: | Half maximal effective concentration |
| EDTA: | Ethylenediaminetetraacetic acid |
| EPP: | Ethyl phenylpropiolate |
| FRAP: | Ferric reducing antioxidant power |
| Gamma-GT: | Gamma-glytamyl transpeptidase |
| IC50: | The half maximal inhibitory concentration |
| LOX: | Lipoxygenase |
| MBC: | Minimum Bactericidal Concentration |
| MDA: | Malonaldehyde |
| MIC: | Minimum inhibitory Concentration |
| NF-kB: | Nuclear factor kappa-light-chain-enhancerof activated B cells |
| OxLDL: | Oxidized low density lipoprotein |
| PLA2: | Phospholipase A2 |
| SGOT: | Serum glutamic oxaloacetic transaminase |
| SGPT: | Serum glutamic-pyruvic transaminase |
| SOD: | Superoxide dismutase |
| TBARS: | Thiobarbituric acid reactive substances |
| TBHQ: | Tertiary Butyl hydroquinone |
| TPA: | 12-O-Tetradecanoylphorbol-13-acetate. |
Conflict of Interests
The authors declare that they have no conflict of interests.