The Scientific World Journal

Review Article

Five Pistacia species (P. vera, P. atlantica, P. terebinthus, P. khinjuk, and P. lentiscus): A Review of Their Traditional Uses, Phytochemistry, and Pharmacology

Table 3

Pharmacological activities of selected Pistacia species.


Pharmacological activity	Plant	Plant part	Assay	Extract/essential oil/isolated component	Dose or concentration	Observations	Ref.

Antioxidant	P. lentiscus	Fruits	In vitro DPPH method	Polyphenols: galic acid (GA) and 1,2,3,4,6 pentagalloyl-glucose (PGA)	1, 3, 10, 30, and 100 µg/mL	Dose dependent radical scavenging activity of GA (IC50: 2 µg/mL) and PGA (IC50: 1 µg/mL)	[52]
			Xanthine oxidase inhibition		100, 200, and 300 µg/mL	formation of uric acid and superoxide anions (O2-) by increasing concentrations of both GA and PGA
			Inhibition of lipid peroxidation induced by H₂O₂ in K562 cell line		200, 400, and 800 µg/mL for GA and 100, 200, and 400 µg/mL for PGA	Dose dependent inhibition by GA (IC50: 220 µg/mL) and PGA (IC50: 200 µg/mL)
		Leaf	Reducing power	Seven different extracts (1) Ethanol, (2) Ethyl acetate, (3) Aqueous/ethyl acetate, (4) Hexane, (5) Aqueous/hexane, (6) Chloroform, (7) Aqueous/chloroform	100 µg/mL	Higher activity of aqueous fractions from hexane and chloroform than standards (BHA and -tocopherol)	[75]
			Linoleic acid peroxidation		100 µg/mL	Inhibition of linoleic acid peroxidation by aqueous extracts from chloroform and hexane comparable to those of the standard (BHA)
			DPPH method		10–100 µg/mL	High scavenging activity (90%) equivalent to that of the standard BHA (89%) by all extracts except chloroform
			Scavenging activity against hydrogen peroxide		100 µg/mL	High scavenging capacity against H₂O₂ comparable to standards (-tocopherol and BHA)
		Aerial parts	DPPH method	Essential oil	0.2, 0.4, 1.0, 2.0, and 4.0 mM	Antioxidant activity ranged between 0.52 and 4.61 mmol/L	[74]
			DPPH method	Methanolic extracts	100, 80, 50, 30, 20, 10, and 5 mg/L	IC50 ranged between 5.09 and 11.0 mg/L	[23]
			FRAP assay		5000 mg/L	Activity ranged between 84.6 and 131.4 mmol Fe2+/L plant extract; IC50: 5.09–11.0 (mg/L)	[23]
	P. lentiscus var. chia	Resin	Oil oxidation assay by the oven test	Resin solution in dichloromethane	0.05, 0.1, and 0.15% w/w	Significant antioxidant activity	[149]
	P. lentiscus	Fruit	ABTS	Digallic acid	0.05, 0.1, 0.15, and 0.2 mg/mL	Free radical scavenging activity towards the ABTS + radical was 99% at 0.2 mg/mL	[47]
			Xanthine oxidase (XO) inhibition and superoxide scavenging activity		50, 100, and 150 µg/mL	21% XO inhibitory activity at 150 µg/mL; 28% reduction of superoxide anion activity
			TBARs		200, 400, and 800 µg/mL	lipid peroxidation (IC50: 178 µg/mL)
		Gum	Electron-spin resonance Spectroscopy for the determination of hydroxyl radical by Fenton reaction	Mastic in water	ND	Effectively scavenged hydroxyl radical generated by the Fenton reaction	[76]
		Gum	Nitrate/nitrite colorimetric assay	Mastic in water	0–3 mg/mL	No nitric oxide scavenging activity	[76]
	P. lentiscus var. chia, P. terebinthus. var. chia	Gum	Copper-induced LDL oxidation	Hexane and methanol/water extracts	2.5, 5, 10, 25, and 50 mg/2 mL	LDL protective activity; methanol/water extract of P. lentiscus showed the most LDL protection	[77]
	P. lentiscus	Leaf	Reduction power activity	Ethanolic extract	0.25; 0.5; 0.75; 1; 2; 3 mg/mL	Reducing power comparable to ascorbic acid	[88]
	P. lentiscus	Leaf	Pyrogallol autoxidation method	Ethanolic extract	ND	Superoxide anions scavenging activity	[88]
	P. atlantica.	Leaf	Reduction power activity	Ethanolic extracts	0.25; 0.5; 0.75; 1; 2; 3 mg/mL	Reducing power close to values observed by ascorbic acid	[88]
	P. atlantica.	Leaf	Pyrogallol autoxidation method	Ethanolic extracts	ND	Superoxide anions scavenger at a concentration as low as 0.0625 mg/mL	[88]
	P. atlantica subsp. mutica	Hull	FRAP test	The unsaponifiable matter (USM) of fruit’s hull oil	100 mg in 10 mL of n-hexane	Significant reducing power; the highest reducing power amongst the USM fractions belonged to the tocopherols and tocotrienols and linear and triterpenic alcohols respectively	[80]
			DPPH radical-scavenging assay		ND	EC50 value significantly lower than α-tocopherol
			Oven test		ND	Significant stabilizing effect
	P. atlantica	Leaf	(1) Reducing power (2) Chelating abilities on metallic ions (3) Radical scavenging Activity (DPPH) (4) The total antioxidant activity (thiocyanate method in linoleic acid emulsion) (5) Hydrogen peroxide scavenging activity	Decoction	(1) 20–100 μg/mL (2) 0.25, 0.50, 0.75, and 1.0 mg/mL (3) 5–25 μg/mL (4) 100 μg/mL (5) 100 μg/mL	(1) Reducing power of significantly higher than -tocopherol and BHT and nearly similar to BHA (2) The chelating activity of 1.0 mg/mL was nearly fourfold less than EDTA at 0.037 mg/mL and has slightly effective capacity for iron binding (3) 85% inhibition rate at 15 μg/mL. nearly similar to ascorbic acid and BHA (4) Higher antioxidant activity than -tocopherol and similar to BHA, BHT, and trolox (5) Concentration-dependent scavenging compared to BHA, BHT, and -tocopherol	[78]
	P. atlantica subsp. mutica	Fruit hull	Rancimat test	-Hexane extract	Different percentages (up to 15%)	The antioxidant activity of hull oil was exactly the same as that of TBHQ at low concentrations	[79]
	P. atlantica	Leaf	DPPH test	Essential oil	50 µL	Weak radical scavenging activity	[32]
	P. atlantica	Leaf	FRAP test	Essential oil	ND	Higher antioxidant capacity relative to ascorbic acid
	P. vera	Fruit hull	Oven test	Water and methanol extracts	0.02%, 0.04%, and 0.06% in soybean oil	Effective in retarding oil deterioration at 60°C; at concentration of 0.06%, similar to BHA and BHT added at 0.02%.	[81]
	P. vera L., var. Bronte	Kernel	ABTS radical cation decolorization assay	Methanol/water or Dichloromethane	ND	The antioxidant activity of the lipophilic extract was much lower than hydrophilic one	[82]
			Lipid peroxidation (TBARS assay)	Hydrophilic extract	0.25, 0.5, or 1.0 mg/mL	Radical scavenging activity in a dose-dependent manner
			Copper-mediated LDL oxidation	Hydrophilic extract	Extracts from 30, 60, or 100 µg of nut	Inhibition of LDL oxidation
		Seed and skin (hull)	DPPH assay	Methanol/water extract	0.050–12.00 mg/mL	Radical scavenging activity	[44]
			Trolox equivalent antioxidant capacity (TEAC) assay (ABTS radical)		ND	Antioxidant power: 0 and mmol Trolox/g of seeds and skins, respectively
			Scavenging activity against the superoxide anion		ND	IC50 of and mg for seeds and skins, respectively
	P. vera	Gum	TBARS and FRAP in rat	Extract	0.1–0.5 g/kg	brain MDA level by 63% and antioxidant power of brain by 235%	[83]
		Hull	DPPH assay	Aqueous	1, 1.5, 2,5, 3,5 and 4 μg/mL	Concentration-dependent radical scavenging activity	[150]
			ABTS assay		ND	Scavenging capacity of crude and purified extracts was higher than standards compounds (TBHQ and BHT)
			-carotene bleaching method		0.48–9.5 μg/mL	Concentration-dependent antioxidant capacity
	P. terebinthus	Leaf	Trolox equivalent antioxidant capacity assay (ABTS/K2S8O2 method)	Ethanol-water extract	ND	Considerably higher antioxidant activity compared with BHA and ascorbic acid	[84]
		Fruits	DPPH test	Acetone and methanol extracts	25, 50 and 100 µg/mL	High radical scavenging activity	[53]
			Total antioxidant activity in -carotene-linoleic acid system		25, 50 and 100 µg	Isolated pure 60-hydroxyhypolaetin-30-methyl Ether showed higher antioxidant activity than both extracts and BHT
			Superoxide anion scavenging activity		50 µg	Both extracts had scavenging activity near to ascorbic acid; higher activity of methanol extract than acetone extract
			FRAP		0.2–1 µg/mL	Higher reducing power of methanol extract than -tocopherol; acetone extract reducing power was equal to that of -tocopherol
			Metal chelating activity		1000–4000 µg/mL	Methanol extract had higher activity than acetone extract
		Fruits and 4 terebinth coffee brands	DPPH radical scavenging activity	Ethyl acetate and methanol extracts	250, 500, 1000 and 2000 µg/mL	High scavenging effect especially at 2000 μg/mL	[85]
			DMPD radical scavenging activity			Scavenging effect lower than that of quercetin
			H₂O₂ radical scavenging activity			Inactive in scavenging H₂O₂ radical
			Metal-chelation effect			Remarkable metal-chelation properties as compared to EDTA
			FRAP assay			High reducing power
			PRAP assay			High reducing power

Antimutagenic	P. lentiscus	Leaf	Aflatoxin B1 (AFB1)-induced mutagenicity in S. typhimurium TA 100	Essential oil	250, 500 and 1000 µg/plate	Mutagenic inhibition of 76.7% by 250, 82.8% by 500, and 96.5% by 1000 µg/plate	[86]
			(AFB1)-induced mutagenicity in S. typhimurium TA100 or TA98	Essential oil	0.3, 250, 500, 1000 µg/plate	In TA100: 76, 82.8, and 96.5%, mutagenic inhibition rate for 250, 500, and 1000 µg/plate, respectively; in TA98: 99 and 100% mutagenic inhibition rate with 250 and 500 µg/plate	[87]
				Aqueous extract	0.3, 50, 300, 600 µg/plate	50 µg/plate: 23% inhibition in TA100 and 52.2% in TA98; 300 and 600 µg/plate: 67.7 and 87.8% for TA100 and 58–76.8% for TA98
				Flavonoid-enriched extract extracts	50, 300, 600 µg/plate	TA100: 47, 75.3, and 88.6% inhibition by 50, 300, and 600 µg/plate, respectively; TA98: 62.5, 77, and 93.5% inhibition by 50, 300, and 600 µg/plate, respectively
			Sodium azide- induced mutagenicity in S. typhimurium TA1535 and TA100	Essential oil	1.5, 10, 15, 30 µg/Plate	TA100: 79, 83, and 94% inhibition by 10, 15, and 30 µg/plate, respectively; TA1535:, 62, 76, and 93% inhibition by 10, 15, and 30 µg/plate, respectively
				Aqueous extract	1.5, 50, 300, 600 µg/plate	TA100: 92, 96, and 98% inhibition by 50, 300, and 600 µg, respectively; TA 1535: 62, 80, and 94% for the same concentrations
				Flavonoid-enriched extract extracts	50, 300, 600 µg/plate	50 and 300 µg/plate: from 54 to 68% inhibition in TA1535 and from 84 to 93% in TA100

Anitmicrobial and antiviral	P. lentiscus	Leaf	Disc diffusion	Essential oil	0.03, 0.15, 0.62, 2.5, 10.0, 40.0 mg/mL	Noticeable activity against S. enteritidis (MIC: 30 µg/mL) and St. aureus (30 µg/mL); less important activity against S. typhimurium, (MIC: 150 µg/mL); No significant inhibitory activity towards Escherichia coli, Pseudomonas aeruginosa, and Enterococcus faecalis	[86]
			Disc diffusion	Ethanolic extract	5 and 10 μL	No effect on Klebsiella pneumoniae and Escherichia coli. Significant inhibition against Candida albicans, Staphylococcus aureus, and Salmonella typhi	[88]
			Disc diffusion	Ethanolic extract	50, 100, 500 μL, and 1 mL	Inhibiting activity on Trichoderma sp and Fusarium sp	[88]
			Disc diffusion	Aqueous extract	ND	Most active against S. typhimurium, (MIC: 4 μg/mL), significant inhibitory activity towards P. aeruginosa and S. enteritidis (MIC: 40 μg/mL), and no activity against S. aureus, E. coli, and Ent. faecalis up to 1000 μg/mL	[87]
			Disc diffusion	Total oligomer flavonoid-enriched extract	ND	TOF extract exhibited antibacterial activity only against S. typhimurium (MIC: 100 μg/mL)
			Microdilution agar	Essential oil	ND	Activity against S. enteritidis, S. typhimurium, and S. aureus (MICs between 30 and 620 μg/mL). No effect on Ent. foecalis, P. aeruginosa, and E. coli up to 1000 μg/mL
	P. lentiscus var. chia	Gum	Disc diffusion	Essential oil and its fractions and components	ND	Escherichia coli, Staphylococcus aureus, and Bacillus subtilis were resistant to -pinene. E. coli is resistant to -myrcene, S. aureus showed an intermediate response, and B. subtilis is sensitive to it. p-Cymene, -caryophyllene, methyl isoeugenol, limonene, -terpinene, and trans-anethole showed moderate antibacterial activity, and in some cases, the bacteria were resistant to them. E. coli and S. aureus were resistant to -pinene, slightly inhibited B. subtilis. Verbenone, R-terpineol, and linalool showed higher antibacterial activity than other components	[19]
		Gum	Disc diffusion	Mastic gum water (MWR) and its major constituents	MWR (58 mg/mL), (−)-trans-pinocarveol (13 mg/mL), (−)-linalool (37.6 mg/mL), -linalool (36.6 mg/mL), (−)-verbenone (29.5 mg/mL), and (+)--terpineol (29.2 mg/mL)	The broadest average inhibition zones were for E. coli and S. aureus by (+)--terpineol and -linalool compared to the positive control (gentamicin 10 µg); significant antifungal activity against Candida albicans by MWR	[33]
		Gum	Microdilution		4%, 2%, 1%, 0.5%, 0.25%, 0.125%, 0.063%, and 0.032% (v/v)	The most potent antimicrobial constituents were -linalool and -terpineol against E. coli and S. aureus. Significant antifungal activity of MWR, -linalool, (−)-verbenone, and (+)--terpineol against C. albicans	[33]
	P. lentiscus	Gum	ND	Liquid mastic	2% liquid mastic	Activity against Porphyromonas gingivalis and Prevotella melaninogenica	[76]
	P. lentiscus	Gum	Human T-cell leukemia MT-4 cells infected with HIV-1_IIIB; viable cell number determination by MTT assay	Solid and liquid mastic	Solid mastic: 0–200 μg/mL; liquid mastic: 0–0.0006%	Neither solid nor liquid mastic had any anti-HIV activity compared to positive controls	[76]
	Pistacia lentiscus var. chia	Gum	Microdilution	Total mastic extract without polymer (TMEWP), acidic and neutral fractions	MEWP: 0.049 to 1.560 mg/mL, fractions: 0.060 to 1.920 mg/mL	The acidic fraction exhibited the highest activity against Helicobacter pylori followed by the TMEWP and neutral fraction	[33]
	Pistacia lentiscus var. chia	Gum	In vivo administration of extract in infected mice with H. pylori	Total mastic extract without polymer (TMEWP)	180 µg/mL	Moderately reduced H. pylori colonization in the antrum and corpus of the mice stomach. Visible reduction in H. pylori colonization observed in histopathology evaluations	[33]
	P. lentiscus, P. atlantica (sp. cabulica, kurdica, and mutica)	Gum	Broth microdilution	Isolated components of the acidic fractions of the gum	ND	The MIC values for the components ranged from 0.1 to 50 μg/mL against the strains of H. pylori and all Gram-negative bacteria including Escherichia coli, Salmonella typhimurium, Serratia marcescens, Pseudomonas aeruginosa, Alcaligenes faecalis, Enterobacter aerogenes Pseudomonas fluorescens, Porphyromonas gingivalis, and Proteus vulgaris and ranged from 2 to 100 μg/mL against Gram-positive bacteria including Bacillus cereus, Staphylococcus aureus, Streptococcus faecalis, Staphylococcus epidermidis, Bacillus subtilis, and Corynebacterium sp	[151]
	P. atlantica (sp. kurdica)	Gum	ND	Essential oil, -pinene	ND	Against all tested bacteria mentioned in previous row, MIC values for essential oil and pure -pinene ranged 500–1000 mg/mL	[152]
	P. atlantica	Leaf and twig	Modified [³H]-hypoxanthine incorporation assay	Flavone 3-methoxycarpachromene from ethyl acetate extract	0.8 and 4.9 µg/mL	IC50 of 3.4 µM against P. falciparum K1 strain where the positive controls artemisinin and chloroquine had IC50s of 3.6 and 89 nM, respectively	[55]
		Leaf and fruit derm	Disk diffusion method	Methanol, ethanol, ethanol + water, and water extracts	25, 50 and 75 mg/mL	Dose dependent activity against E. coli, Staphylococcus aureus, and Staphylococcus epidermidis; less activity in comparison with gentamicin (10 μg/disk), tobramycin (10 μg/disk), and kanamycin (30 μg/disk)	[91]
		Leaf	Disc diffusion	Ethanolic extract	5 and 10 μL	Klebsiella pneumoniae and Escherichia coli were not sensitive to the extract. Candida albicans, Staphylococcus aureus, and Salmonella typhi showed a sensitizing effect at the 5 μL and a very significant effect at 10 μL	[88]
		Leaf	Disc diffusion	Ethanolic extract	(50, 100, 500 μL, and 1 mL) of ethanolic extract (0.338 g/mL)	No inhibiting activity was observed against Aspergillus flavus, Rhizopus stolonifer, Trichoderma sp, Fusarium sp and Aspergillus flavus	[88]
		Gall	Disc diffusion	Aqueous extract	4.9 mg	Activity against the Bacillus species and Pseudomonas aeruginosa	[92]
		Leaf and gall	Disc diffusion	Essential oils	Final 0.1% v/v	Delayed not block fungal growth in Fomitopsis pinicola and Penicillium sp. by volatile constituents of galls; volatile constituents of leaf inhibited only the growth of Penicillium sp	[92]
		Gum	Agar disc diffusion	Essential oil	10⁻¹, 10⁻², 10⁻³, and 10⁻⁴ μg/mL	Most active against E. coli followed by S. aureus and S. pyogenes.	[90]
			Inhibitory quantity (MIQ) method		0.5, 1, 1.5, and 2 μg/mL	S. aureus and S. pyogenes were susceptible to 0.5 μg/mL, and E. coli was tolerant to this concentration
			Maruzzella method		10⁻¹, 10⁻², 10⁻³ μg/mL	E. coli, Staphylococcus aureus, and Streptococcus pyogenes were sensitive to 10⁻¹ μg/mL
	P. atlantica var. kurdica	Gum	Mice infected with Leishmania major	Gum	Locally rubbed on lesions	Skin lesion size in mice infected with L. major compared with control ; number of parasitologicaly positive mice	[93]
	P. terebinthus	Leaf	Microdilution	Hydroalocholic extract	0.024, 0.049, 0.097, 0.19, 0.78, 1.56, and 25 mg/mL (for S. aureus) 0.049–12.5 mg/mL (for E. coli)	Activity against S. aureus with a MIC: ≤1.56 mg/mL. No antimicrobial effect on E. coli.	[84]
	P. terebinthus	Gum	Disc diffusion, microdilution	Essential oil and gum smoke	ND	Activity of essential oil against all tested bacteria including Bacillus subtilis, Salmonella typhi, Escherichia coli, Staphylococcus epidermidis, and Pseudomonas aeruginosa; activity of nonpolar smoke fraction on all of strains especially on S. dysenteriae, E. coli, B. subtilis, and P. aeruginosa	[140]
	P. khinjuk	Not mentiond	Disc diffusion, microdilution	Ethanolic extract and its fractions	ND	Active against Gram-positive and Gram-negative bacteria especially n-butanolic fraction	[153]
		Leaf	Microdilution	Chloroform, ethyl acetate, ethyl alcohol, and diethyl ether extracts	ND	Activity against bacteria including Bacillus subtilis, Enterococcus faecalis, Staphylococcus aureus Staphylococcus epidermidis, Escherichia coli, and Klebsiella pneumoniae (MIC = 0.02–0.5 mg/mL) and fungi including Candida albicans and Saccharomyces cerevisiae (MIC = 0.06–0.4 mg/mL). Chloroform extract inhibited growth of fungi more than others	[38]
		Leaf, fruits derm	Disc diffusion	Methanolic extract	25, 50, 75 mg/mL	Hydroalcoholic extract of fruits derm on E. coli, water extract on S. epidermidis, and methanolic extract on S. aureus (all in 75 mg/mL) had higher antibacterial activity than tobramycin and same as gentamicin and kanamycin	[91]
	P. vera	Leaf, branch, stem, seed	In vitro study on four parasitic protozoa	Lipophylic extracts	0.8 to 9.7 µg/mL	No inhibitory activity against Trypanosoma brucei rhodesiense	[94]
						Not any significant inhibitory potential against Trypanosoma cruzi
						Remarkable activity of branches extract at 4.8 µg/mL against Leishmania donovani
						Dried leaf extract displayed notable activity against Plasmodium falciparum at 4.8 µg/mL
		Gum	Hole-plate, agar dilution	Essential oil	1/10, 1/20, 1/40, 1/80, and 1/100 v/v	All isolates of Helicobacter pylori were sensitive to the essential oil (MIC: 1.55 µg/mL)	[15]
		Gum	Agar-disc diffusion, broth microdilution, and broth susceptibility	Essential oil	of 2 and 4 µL	Dose dependent activities against Corynebacterium xerosis, Bacillus brevis, B. megaterium, Mycobacterium smegmatis, St. aureus, Klebsiella oxytoca, Enterococcus faecalis, Micrococcus luteus, Escherichia coli, Yersinia enterocolitica, Kluyveromyces fragilis Rhodotorula rubra, and Candida albicans	[12]
		Hull	Disk diffusion test	Aqueous	1200 μg/plate	Gram positive bacteria were the most sensitive	[150]
		Hull	Agar dilution method	Aqueous	0.5 to 10 mg/mL	Gram positive bacteria were the most sensitive	[150]
		Leaf, branch, stem, kernel, shell skins, and seeds	Microdilution	Lipophylic extracts	256 and 512 mg/mL	Greater activity against Gram positive bacteria than Gram-negative; remarkable antifungal activity against C. albicans and C. parapsilosis	[89]
		Leaf, branch, stem, kernel, shell skins, and seeds	In vitro antiviral assay	Lipophylic extracts	256 and 512 mg/mL	Extracts of shell skin and fresh kernel had significant activity against Parainfluenza virus and Herpes simplex virus same as the acyclovir	[89]

Anti-inflammatory	P. terebinthus	Gall	Phospholipase A2 (PLA2) induced hind-paw mouse edema	Methanolic extract	200 mg/kg	Inhibition of edema	[95]
			Ethyl phenylpropiolate (EPP) induced mouse ear edema		1 mg/ear	Inhibition of edema by 44%.
			12-O-Tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema		1 mg/ear	Nonsignificant effect
			Mouse ear edema induced by multiple topical applications of TPA		1 mg/ear	58% inhibition of chronic inflammatory swelling
			In vitro phospholipase A2 activity assay		ND	activity of the enzyme by 75%
			Myeloperoxidase assay		ND	activity of the enzyme by 73%
			Phospholipase A2 (PLA2)-induced hind-paw mouse edema	Masticadienonic acid, masticadienolic acid, and morolic acid from methanolic extract	30 mg/kg	Inhibition of edema by all triterpenes	[95]
			Ethyl phenylpropiolate (EPP) induced mouse ear edema		1 mg/ear	31% and 38% nonsignificant inhibition of edema by masticadienolic acid and morolic acid, whereas masticadienonc acid was inactive
			Mouse ear edema induced by multiple topical applications of TPA		0.3 mg/ear	Inhibition of swelling and neutrophil infiltration by all compounds
			Myeloperoxidase assay		10–100 µg/mL	80% inhibition of enzyme activity by all the compounds
			Inhibition of the production of LTB4 from rat polymorphonuclear leukocytes (PMNL)		12.5–100 µM	Inhibition of leukotriene B4 production in rat PMNL by all compounds
			Ethyl phenylpropiolate-induced mouse ear oedema	Oleanolic acid and its semisynthetic 3-oxo-analogue	1 mg/ear	No activity on the edema	[95]
			Mouse ear edema induced by TPA		0.5 mg/ear	A nonsignificant 28% inhibition
			Mouse edema induced by DPP		0.5 mg/ear	swelling by 40% similar to standard (carbamazepine)
			Delayed type hypersensitivity induced by fluorobenzene in mouse ear	Oleanolic and oleanonic acids	0.5 mg/ear	Oleanonic acid: ineffective at both 24 and 96 h; oleanolic acid: edema nonsignificantly at 96 h by 32%
			Mouse ear inflammation induced by multiple topical applications of TPA		0.3 mg/ear	Oleanonic acid: significant effect with 45% inhibition; oleanolic acid: inactive
			Myeloperoxidase assay		ND	Inhibition of neutrophil infiltration by oleanonic and oleanolic 84% and 67%, respectively
			Phospholipase A2-induced hind paw mouse edema		30 mg/kg	edema by both compounds
			Bradykinin-induced mouse paw edema	Oleanonic acid	30 mg/kg	edema by 61%
			Inhibition of leukotriene B4 production from rat polymorphonuclear leukocytes	Oleanonic acid	ND	leukotriene B4 (IC50: 17 µM)
	P. vera	Fruits, leaf, branches, peduncles, and oleoresin	Carrageenan-induced hind paw edema	Ethanolic and aqueous extracts	250, 500 mg/kg	Among all extracts, only the oleoresin exhibited a dose-dependent anti-inflammatory activity	[146]
		Fruits, leaf, branches, peduncles, and oleoresin	p-Benzoquinone-induced abdominal constriction test in mice	Ethanolic and aqueous extracts	250, 500 mg/kg	Among all extracts, only the oleoresin displayed antinociceptive activity with 32.1% inhibition at 500 mg/kg and 21.7% inhibition at 250 mg/kg	[146]
		Leaf	Hot plate test	Aqueous extract, ethanolic extract	0.4 and 0.5 g/Kg	Dose-dependent antinociceptive activity after 30–60 min of treatment	[97]
			Xylene-induced ear edema	Aqueous extract	0.4, 0.16, 0.28 g/kg	Significant anti-inflammatory activities
			Chronic anti-inflammatory activity (granuloma pouch method)	Aqueous extract, ethanolic extract	0.4 g/Kg 0.35, 0.5 g/Kg	Significant and dose-dependent anti-inflammatory activity
			Writhing test	Aqueous extract ethanolic extract	0.4, 0.28 g/kg 0.35, 0.5 g/Kg	number of mouse abdominal constrictions induced by acetic acid
	P. lentiscus var. chia	Gum	Modification of VCAM-1 and ICAM1 expression by ELAISA	Neutral extract and isolated phytosterol tirucallol	Extract: 25, 50, 100, 200 µg/mL Tirucallol: 0.1, 1, 10, 100 µM	significant dose-dependent in vascular adhesion molecule 1 (VCAM-1) and intracellular adhesion molecule 1 (ICAM-1) expression	[98]
			U937 cell adhesion assay			adhesion of U937 cells to TNF--stimulated human aortic endothelial cells
			Measurement of NFkB p65 phosphorylation by ELISA			phosphorylation of NFkB p65

Effects on Gastrointestinal disorders	P. lentiscus	Resin	Pyloric ligation-, Aspirin-, phenylbutazone-, and reserpine-induced and cold-restraint stress ulcer in rat	Powder finely suspended in corn oil	An oral dose of 500 mg/kg	intensity of gastric mucosal damage in all models	[103]
	P. lentiscus	Resin	TNBS-induced colitis in rats	Powder in polyherbal formulation	50, 100, and 200 mg/kg of formula with 4% P. lentiscus resin	macroscopic and microscopic colonic damage; TNF-, IL-1, MPO, and lipid peroxidation; not significantly increase in antioxidant power of colon	[106]
	P. lentiscus var. chia.	Resin	3-week double-blind randomised placebo controlled study on patients with functional dyspepsia	Powder	350 mg TID	Improved the feeling of symptoms significantly	[104]
	P. lentiscus var. chia.	Resin	Dextran-sulfate sodium (DSS) model of colitis in mice	Powder	0.20 g/kg chow (0.02%) 2.0 g/kg chow (0.20%)	Delayed the onset and progression of acute colitis and weight loss caused by the disease	[105]
	P. lentiscus var. chia.	Resin	4-week pilot study on 10 patients with Crohn’s disease and 8 controls	Capsules of fine powder	2.22 g/day (6 caps/d, 0.37 g/cap)	Crohn’s disease activity index and plasma inflammatory mediators such as C-reactive protein, interleukin-6 (IL-6) without any side effects; immunomodulatory effect by tumor necrosis factor-alpha (TNF-) and ↑macrophage migration inhibitory factor	[107]
	P. lentiscus var. chia	Resin	4-week pilot study on 10 patients with crohn’s disease and 8 controls	Capsules of fine powder	2.22 g/day (6 caps/d, 0.37 g/cap)	Immunomodulatory activity TNF- and macrophage migration inhibitory factor (MIF) in these patients	[108]

Antidiabetic	P. atlantica	Leaf	In vitro and in vivo (normoglycemic and streptozocin-induced hyperglycemic rats)	Aqueous extract	2 mL plant extract equivalent to 200 mg of starting material	Significant inhibitory effect on -amylase in vitro; no significant hypoglycemic activity in normoglycemic and hyperglycemic rats	[109]
	P. atlantica	Leaf	In vitro enzymatic starch digestion and rat model	Aqueous extract	1, 5, 10, 12.5, 25, 50, and 100 mg/mL 125, 250, and 500 mg/kg	In vitro: significant dose dependent dual inhibition of -amylase and -glucosidase comparable to acarbose In vivo: significant acute postprandial antihyperglycemic activity comparable to metformin and glipizide and improved glucose intolerance in oral starch tolerance test	[110]
	P. lentiscus var. chia	Resin	Human study	Powder diluted in 250 mL of water	0.7 g per day	Significantly decrease (3.1 mg/dL per month, ) in serum glucose level among male subjects	[111]

Antitumor	P. lentiscus var. chia	Resin	In vitro study on human colon cancer cells (HCT116)	Ethanol extract	ND	Inhibited proliferation and induced apoptosis of human colorectal tumor cells	[112]
	P. lentiscus	Resin	In vitro study on human leukemic cell line	Liquid and solid resin	0–200 μg/mL (solid mastic) or 0–2 (v/v)% of liquid mastic	The most cytotoxic effect against promyelocytic leukemia HL-60 among 13 human cell types; inhibition of natural apoptosis of oral polymorphonuclear leukocytes	[76]
			In vivo human colon cancer/immunodeficient mouse model	Hexane extract	200 mg/kg administered daily for 4 consecutive days (followed by 3 days without treatment)	Anticancer activity via its delay effect on the growth of colorectal tumors developed from HCT116 xenografted into mice	[8]
			Human cell line (androgen-responsive prostate cancer cell line)	ND	2, 4, 6, 8, 10, and 12 µg/mL	Remarkable potency to decrease the expression and function of the androgen receptor in androgen-responsive prostate cancer cell line (LNCaP)	[154]
			Human prostate cancer cell lines (LNCaP and DU-145), RT-PCR, and Western blotting were used to detect maspin expression	ND	2, 4, 6, and 8 µg/mL	Increased maspin expression in LNCaP cells	[113]
			The human prostate cancer cell lines (PC-3), MTT assay, gene assay, RT-PCR, and Western blotting	ND	10, 20, and 30 µg/mL	Inhibited proliferation and blocked the cell cycle progression in androgen-independent prostate cancer PC-3 cells by suppressing NF-κB activity and the NF-κB signal pathway	[114]
			Lewis lung carcinoma cells	Essential oil	0.01% v/v	A time-dependent modification in the expression of 925 genes and phenomena in Lewis lung carcinoma cells by its antiproliferative, proapoptotic, and anti-inflammatory activities	[155]
	P. atlantica sub. kurdica	Fruit	Immunocompetent mice	Essential oil	45 mg/kg intraperitoneally, 3 times a week for 3 weeks	Significant inhibition on tumor growth without signs of toxicity related to apoptosis induction, reduced neovascularization, and inhibiting chemokine expression	[115]
			Cells line and the in vivo chicken embryo CAM angiogenesis model	Essential oil	0.01–0.1% v/v	Antiproliferative and proapoptotic effect on K562 human leukemia cells; inhibited the release of vascular endothelial growth factor from K562 and B16 mouse melanoma cell; concentration-dependent inhibition of endothelial cell proliferation without affecting cell survival; significant decrease of microvessel formation	[116]
			Rat liver medium-term carcinogenesis bioassay (Ito-test)	Powder in diet	0, 0.01, 0.1 and 1%	Promoted the preneoplastic lesions development in rat liver with increasing liver relative weight	[117]
			human colon carcinoma HT29 cells	Ethanol : H₂O (70 : 30)	0.7 mg/mL	50% growth inhibition similar to 500 nM of doxorubicin	[119]
	P. vera	Resin	In vitro cytotoxic activity against human cell lines	Crud methanolic extract fractionated against petroleum ether, chloroform, and n-butanol	ND	Moderate cytotoxic effect against breast cancer cell line (MCF7), hepatocellular carcinoma cell line (HEPG2), cervix cancer cell line (HELA), and normal melanocytes (HFB4); n-hexane fraction showed strong cytotoxic effect (IC50: 3.15–4.17 µg/mL) against all of the tested cell lines, except for MCF7 (IC50: 13.5 µg/mL)	[120]

Effects on liver and serum biochemical parameters	P. lentiscus	Leaf	Rat model using Carbon tetrachloride	Aqueous extract	4 mL/kg (contained 1.946 g of solid matter)	bilirubin and activity of 3 enzymes including alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST)	[121]
	P. lentiscus	Leaf	Rat model using Thioacetamide	Aqueous extract	15 mg/kg and 75 mg/kg	Hepatic fibrosis, an inflammatory response, mild cholestasis, and depletion of reduced glutathione associated with an increase in its oxidized form for five weeks administration in healthy rats; in thioacetamide-induced rat liver lesions, it aggravated the inflammatory, fibrotic, and glutathione depleting responses without affecting the extent of lipid peroxidation	[122]
	P. lentiscus var. chia	Resin	Human model	Powder diluted in one glass (250 mL) of water	5 g	Serum total cholesterol, LDL, total cholesterol/HDL ratio, lipoprotein, apolipoprotein A-1, apolipoprotein B, AST, ALP, and gamma-GT were reduced in human subjects	[111]
	P. lentiscus	Seeds oil	Rabbit model, mercury induced toxicity	Pistacia oil	5%	Mercury induced toxicity in rabbits caused increase in the level of ALP, AST, and urea serum, while it was reported that P. lentiscus oil-treated rabbits showed none of those changes	[156]
	P. vera	Fruit (roasted, unsalted pistachio nuts)	Human model (10 patients with moderate hypercholesterolemia)	Nut	20% in diet	total cholesterol, total cholesterol/HDL ratio, and LDL/HDL ratio and HDL after 3 weeks use	[124]
	P. terebinthus	Fruit	Rabbit model	Fruit	1 g/kg	Inhibited the development of hydropic degeneration and fatty changes in the liver and demonstrated hypolipidemic effect	[125]

Effects on atherosclerosis	P. vera	Fruit	Rabbit model	Methanolic and cyclohexane extracts	Methanolic extract (1% v/w) cyclohexane extract (5% v/w)	Beneficial effects on HDL, LDL, and aortic intimal thickness. The methanolic extract additionally showed an antioxidant activity and remarkable decrease in aortic surface lesions	[123]
	P. terebinthus	Fruit	Rabbit model	Fruit	1 g/kg	Inhibited the development of the atherosclerotic lesions in the thoracic artery	[125]
	P. lentiscus	Resin	Cell culture (peripheral blood mononuclear cell, PBMC); cell viability assessed via MTT assay	Total polar extract	2.7, 27, and 270 µg/mL	Restored intracellular antioxidant glutathione (GSH) levels and downregulated CD36 mRNA expression resulted in antioxidant and antiatherogenic effects	[126]

Anticholinesterase activity	P. atlantica	leaf	TLC bioautography assay, Ellman’s colorimetric method	Aqueous extract	5, 10, 15, 20, and 25 µg/mL	Strong acetylcholinesterase (AChE) inhibition	[13]
	P. atlantica	Leaf	Ellman’s colorimetric method	Methanol and ethyl acetate extracts	0.1 mg/mL	Relatively weak AChE inhibitory activity	[127]
	P. terebinthus	Fruit	Ellman’s colorimetric method and the modified dopachrome method	Ethyl acetate and methanol extracts	25, 50, 100, and 200 µg/mL	No inhibitory activity against AChE and tyrosinase while selectively inhibited butyrylcholinesterase (BChE) at moderate levels (below 50%) at the tested concentrations	[85]