The Scientific World Journal / 2013 / Article / Tab 3

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 activityPlantPlant partAssay Extract/essential oil/isolated componentDose or
concentration
ObservationsRef.

Antioxidant P.  lentiscus FruitsIn 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 inhibition100, 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 line200, 400, and 800 µg/mL for GA and 100, 200, and 400 µg/mL for PGADose dependent inhibition by GA (IC50: 220 µg/mL) and PGA (IC50: 200 µg/mL)
LeafReducing 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/mLHigher activity of aqueous fractions from hexane and chloroform than standards (BHA and -tocopherol) [75]
Linoleic acid peroxidation100 µg/mLInhibition of linoleic acid peroxidation by aqueous extracts from chloroform and hexane comparable to those of the standard (BHA)
DPPH method10–100 µg/mLHigh scavenging activity (90%) equivalent to that of the standard BHA (89%) by all extracts except chloroform
Scavenging activity against hydrogen peroxide100 µg/mLHigh scavenging capacity against H2O2 comparable to standards ( -tocopherol and BHA)
Aerial partsDPPH methodEssential oil 0.2, 0.4, 1.0, 2.0, and 4.0 mMAntioxidant activity ranged between 0.52 and 4.61 mmol/L[74]
DPPH methodMethanolic
extracts
100, 80, 50, 30, 20, 10, and 5 mg/LIC50 ranged between 5.09 and 11.0 mg/L[23]
FRAP assay5000 mg/LActivity ranged between 84.6 and 131.4 mmol Fe2+/L plant extract; IC50: 5.09–11.0 (mg/L)
P.  lentiscus var. chia ResinOil oxidation assay by the oven test Resin solution in dichloromethane0.05, 0.1, and 0.15% w/wSignificant antioxidant activity [149]
P.  lentiscus Fruit ABTS Digallic acid 0.05, 0.1, 0.15, and 0.2 mg/mLFree radical scavenging activity towards the ABTS + radical was 99% at 0.2 mg/mL [47]
Xanthine oxidase (XO) inhibition and superoxide scavenging activity50, 100, and 150 µg/mL 21% XO inhibitory activity at 150 µg/mL; 28% reduction of superoxide anion activity
TBARs200, 400, and 800 µg/mL lipid peroxidation (IC50: 178 µg/mL)
GumElectron-spin resonance Spectroscopy for the determination of hydroxyl radical by Fenton reaction Mastic in waterNDEffectively scavenged hydroxyl radical generated by the
Fenton reaction
[76]
Nitrate/nitrite
colorimetric assay
0–3 mg/mLNo nitric oxide scavenging activity
P.  lentiscus  var. chia, P.  terebinthus.  var. chia GumCopper-induced LDL oxidationHexane and methanol/water extracts2.5, 5, 10, 25, and 50 mg/2 mLLDL protective activity;
methanol/water extract of P.  lentiscus showed the most LDL protection
[77]
P.  lentiscus LeafReduction power activityEthanolic extract0.25; 0.5; 0.75;
1; 2; 3 mg/mL
Reducing power comparable to ascorbic acid [88]
Pyrogallol autoxidation methodNDSuperoxide anions scavenging activity
P.  atlantica. LeafReduction power activityEthanolic extracts0.25; 0.5; 0.75;
1; 2; 3 mg/mL
Reducing power close to values observed by ascorbic acid [88]
Pyrogallol autoxidation methodNDSuperoxide anions scavenger at a concentration as low as 0.0625 mg/mL
P.  atlantica  
subsp. mutica
HullFRAP test The unsaponifiable matter (USM) of fruit’s hull oil100 mg in 10 mL of n-hexaneSignificant 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 assayND
EC50 value significantly lower than α-tocopherol
Oven testNDSignificant 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 hullRancimat
test
-Hexane extractDifferent 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 testEssential oil50 µL Weak radical scavenging activity [32]
FRAP testNDHigher antioxidant capacity relative to ascorbic acid
P.  vera Fruit hullOven testWater and methanol extracts0.02%, 0.04%, and 0.06% in soybean oilEffective 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 KernelABTS radical cation decolorization assayMethanol/water or
Dichloromethane
ND The antioxidant activity of the lipophilic extract was much lower than hydrophilic one[82]
Lipid peroxidation
(TBARS assay)
Hydrophilic extract0.25, 0.5, or 1.0 mg/mL Radical scavenging activity in a dose-dependent manner
Copper-mediated LDL oxidationHydrophilic extractExtracts from 30, 60, or 100 µg of nutInhibition of LDL oxidation
Seed and skin (hull)DPPH assay Methanol/water extract0.050–12.00 mg/mL Radical scavenging activity[44]
Trolox equivalent antioxidant capacity (TEAC) assay
(ABTS radical)
NDAntioxidant power: 0 and  mmol Trolox/g of seeds and skins, respectively
Scavenging activity against the superoxide anionNDIC50 of and  mg for seeds and skins, respectively
P.  vera GumTBARS and FRAP in ratExtract 0.1–0.5 g/kg brain MDA level by 63% and antioxidant power of brain by 235% [83]
HullDPPH assay Aqueous1, 1.5, 2,5, 3,5 and 4 μg/mLConcentration-dependent radical scavenging activity [150]
ABTS assayNDScavenging capacity of crude and purified extracts was higher than standards compounds (TBHQ and BHT)
-carotene bleaching method0.48–9.5 μg/mLConcentration-dependent antioxidant capacity
P.  terebinthus Leaf Trolox equivalent antioxidant capacity assay (ABTS/K2S8O2 method)Ethanol-water extractNDConsiderably higher antioxidant activity compared with BHA and ascorbic acid [84]
FruitsDPPH testAcetone and methanol extracts25, 50 and 100 µg/mLHigh radical scavenging activity [53]
Total antioxidant activity in -carotene-linoleic acid system 25, 50 and 100 µgIsolated pure 60-hydroxyhypolaetin-30-methyl
Ether showed higher antioxidant activity than both extracts and BHT
Superoxide anion scavenging activity50 µgBoth extracts had scavenging activity near to ascorbic acid; higher activity of methanol extract than acetone extract
FRAP0.2–1 µg/mLHigher reducing power of methanol extract than -tocopherol; acetone extract reducing power was equal to that of -tocopherol
Metal chelating activity1000–4000 µg/mLMethanol extract had higher activity than acetone extract
Fruits and 4 terebinth coffee brandsDPPH radical scavenging activityEthyl acetate and methanol extracts250, 500, 1000 and 2000 µg/mL High scavenging effect especially at 2000 μg/mL [85]
DMPD radical scavenging activityScavenging effect lower than that of quercetin
H2O2 radical scavenging activityInactive in scavenging H2O2 radical
Metal-chelation effectRemarkable metal-chelation properties as compared to
EDTA
FRAP assayHigh reducing power
PRAP assayHigh reducing power

Antimutagenic P.  lentiscus LeafAflatoxin B1 (AFB1)-induced mutagenicity in S.  typhimurium TA 100 Essential oil250, 500 and 1000 µg/plateMutagenic 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 TA98Essential 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 extract0.3, 50, 300, 600 µg/plate50 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 extracts50, 300, 600 µg/plateTA100: 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/PlateTA100: 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 extract1.5, 50, 300, 600 µg/plateTA100: 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 extracts50, 300, 600 µg/plate50 and 300 µg/plate: from 54 to 68% inhibition in TA1535 and from 84 to 93% in TA100

Anitmicrobial and antiviral P.  lentiscus LeafDisc diffusionEssential oil0.03, 0.15, 0.62, 2.5, 10.0, 40.0 mg/mLNoticeable 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 diffusionEthanolic 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 NDTOF extract exhibited antibacterial activity only against S. typhimurium  (MIC: 100 μg/mL)
Microdilution agar Essential oil NDActivity 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 GumDisc diffusion Essential oil and its fractions and componentsNDEscherichia 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]
GumDisc 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]
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
P.  lentiscusGumNDLiquid mastic2% liquid masticActivity against Porphyromonas gingivalis and Prevotella melaninogenica [76]
Human T-cell leukemia MT-4 cells infected with HIV-1IIIB; viable cell number determination by MTT assaySolid and liquid masticSolid mastic: 0–200 μg/mL; liquid mastic: 0–0.0006%Neither solid nor liquid mastic had any anti-HIV activity compared to positive controls
Pistacia lentiscus  var. chia GumMicrodilutionTotal mastic extract without polymer (TMEWP),
acidic and neutral fractions
MEWP: 0.049 to 1.560 mg/mL, fractions: 0.060 to 1.920 mg/mLThe acidic fraction exhibited the highest activity against Helicobacter pylori followed by the TMEWP and neutral fraction [33]
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
P.  lentiscus,
P.  atlantica
(sp.  cabulica, kurdica, and mutica)
GumBroth microdilution Isolated components of the acidic fractions of the gumND 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)
GumNDEssential 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 twigModified [3H]-hypoxanthine incorporation assay
Flavone 3-methoxycarpachromene from ethyl acetate extract0.8 and 4.9 µg/mLIC50 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 dermDisk diffusion methodMethanol, ethanol,
ethanol + water, and water extracts
25, 50 and 75 mg/mLDose 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]
LeafDisc diffusion Ethanolic extract5 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]
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
Gall Disc diffusion Aqueous extract4.9 mg Activity against the Bacillus species and Pseudomonas aeruginosa [92]
Leaf and gallDisc diffusion Essential oilsFinal 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
GumAgar disc diffusionEssential oil10−1, 10−2, 10−3, and 10−4μg/mLMost active against E. coli followed by S. aureus and S.  pyogenes. [90]
Inhibitory quantity (MIQ) method0.5, 1, 1.5, and 2 μg/mLS. aureus and S. pyogenes were susceptible to 0.5 μg/mL, and E. coli was tolerant to this concentration
Maruzzella method10−1, 10−2, 10−3μg/mLE. coli, Staphylococcus aureus, and Streptococcus pyogenes were sensitive to 10−1μg/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 LeafMicrodilution Hydroalocholic extract0.024, 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]
GumDisc diffusion,
microdilution
Essential oil and gum smokeNDActivity 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 mentiondDisc diffusion,
microdilution
Ethanolic extract and its fractions
NDActive against Gram-positive
and Gram-negative bacteria especially n-butanolic fraction
[153]
LeafMicrodilution Chloroform, ethyl acetate,
ethyl alcohol, and diethyl ether extracts
NDActivity 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 dermDisc diffusion Methanolic extract25, 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 protozoaLipophylic extracts0.8 to 9.7 µg/mLNo 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
GumHole-plate,
agar dilution
Essential oil1/10, 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]
Agar-disc diffusion, broth microdilution, and broth susceptibility Essential oilof 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]
HullDisk diffusion testAqueous1200 μg/plateGram positive bacteria were the most sensitive [150]
Agar dilution method0.5 to 10 mg/mL
Leaf, branch, stem, kernel,
shell skins, and seeds
Microdilution Lipophylic extracts256 and 512 mg/mLGreater activity against Gram positive bacteria than Gram-negative; remarkable antifungal activity against C.  albicans and C. parapsilosis [89]
In vitro antiviral assay Extracts of shell skin and fresh kernel had significant activity against Parainfluenza virus and Herpes simplex virus same as the acyclovir

Anti-inflammatory P. terebinthus GallPhospholipase A2 (PLA2)
induced hind-paw mouse edema
Methanolic extract200 mg/kgInhibition of edema [95]
Ethyl phenylpropiolate (EPP) induced mouse
ear edema
1 mg/earInhibition of edema by 44%.
12-O-Tetradecanoylphorbol-13-acetate
(TPA)-induced mouse ear edema
1 mg/earNonsignificant effect
Mouse ear edema induced by multiple topical applications of TPA1 mg/ear58% inhibition of chronic inflammatory swelling
In vitro phospholipase A2 activity assayND activity of the enzyme by 75%
Myeloperoxidase assayND activity of the enzyme by 73%
Phospholipase A2 (PLA2)-induced hind-paw mouse edemaMasticadienonic acid, masticadienolic acid, and morolic acid from methanolic extract30 mg/kgInhibition of edema by all triterpenes [95]
Ethyl phenylpropiolate (EPP) induced mouse
ear edema
1 mg/ear31% 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/earInhibition of swelling and neutrophil infiltration by all compounds
Myeloperoxidase assay10–100 µg/mL80% inhibition of enzyme activity by all the compounds
Inhibition of the production of LTB4 from rat polymorphonuclear leukocytes (PMNL)12.5–100 µMInhibition of leukotriene B4 production in rat PMNL by all compounds
Ethyl phenylpropiolate-induced mouse ear oedemaOleanolic acid and its semisynthetic 3-oxo-analogue1 mg/earNo activity on the edema [95]
Mouse ear edema induced by TPA0.5 mg/earA nonsignificant 28% inhibition
Mouse edema induced by DPP0.5 mg/ear swelling by 40% similar to standard (carbamazepine)
Delayed type hypersensitivity induced by fluorobenzene
in mouse ear
Oleanolic and oleanonic acids0.5 mg/earOleanonic 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 TPA0.3 mg/earOleanonic acid: significant effect with 45% inhibition; oleanolic acid: inactive
Myeloperoxidase assayNDInhibition of neutrophil infiltration by oleanonic and oleanolic 84% and 67%, respectively
Phospholipase A2-induced hind paw mouse edema30 mg/kg edema by both compounds
Bradykinin-induced mouse paw edemaOleanonic acid30 mg/kg edema by 61%
Inhibition of leukotriene B4 production from rat
polymorphonuclear leukocytes
ND leukotriene B4 (IC50: 17 µM)
P.  vera Fruits,
leaf, branches,
peduncles, and oleoresin
Carrageenan-induced hind paw edemaEthanolic and aqueous extracts250, 500 mg/kgAmong all extracts, only the oleoresin exhibited a dose-dependent anti-inflammatory activity [146]
p-Benzoquinone-induced abdominal constriction test
in mice
250, 500 mg/kgAmong all extracts, only the oleoresin displayed antinociceptive activity with 32.1% inhibition at 500 mg/kg and 21.7% inhibition at 250 mg/kg
LeafHot plate testAqueous extract,
ethanolic extract
0.4 and 0.5 g/Kg Dose-dependent antinociceptive activity after 30–60 min of treatment[97]
Xylene-induced ear edemaAqueous extract0.4, 0.16, 0.28 g/kgSignificant anti-inflammatory activities
Chronic anti-inflammatory activity (granuloma pouch method)Aqueous extract, ethanolic extract0.4 g/Kg
0.35, 0.5 g/Kg
Significant and dose-dependent anti-inflammatory activity
Writhing testAqueous 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. chiaGum 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 disordersP.  lentiscus ResinPyloric 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 ResinTNBS-induced colitis in ratsPowder in polyherbal formulation50, 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.Resin3-week double-blind randomised placebo controlled study on patients with functional dyspepsiaPowder 350 mg TIDImproved the feeling of symptoms significantly [104]
P.  lentiscus var. chia.ResinDextran-sulfate sodium (DSS) model of colitis in micePowder0.20 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.Resin4-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 Resin4-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]

AntidiabeticP.  atlantica Leaf In vitro and in vivo (normoglycemic and streptozocin-induced hyperglycemic rats) Aqueous extract2 mL plant extract equivalent to 200 mg of starting materialSignificant inhibitory effect on -amylase in vitro; no significant hypoglycemic activity in normoglycemic and hyperglycemic rats[109]
In vitro enzymatic starch digestion and rat model Aqueous extract1, 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 studyPowder diluted in 250 mL of water0.7 g per day Significantly decrease (3.1 mg/dL per month, ) in serum glucose level among male subjects[111]

AntitumorP.  lentiscus var. chia Resin In vitro study on human colon cancer
cells (HCT116)
Ethanol extractNDInhibited proliferation and induced apoptosis of human colorectal tumor cells[112]
P.  lentiscus Resin In vitro study on human leukemic cell line Liquid and solid resin0–200 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 modelHexane extract200 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)ND2, 4, 6, 8, 10, and 12 µg/mLRemarkable 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 expressionND2, 4, 6, and 8 µg/mLIncreased maspin expression in LNCaP cells[113]
The human prostate cancer cell lines (PC-3), MTT assay, gene assay, RT-PCR, and
Western blotting
ND10, 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 cellsEssential oil0.01% v/vA 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. kurdicaFruit Immunocompetent mice Essential oil45 mg/kg intraperitoneally, 3 times a week for 3 weeksSignificant 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 oil0.01–0.1% 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 diet0, 0.01, 0.1 and 1%Promoted the preneoplastic lesions development in rat liver with increasing liver relative weight [117]
human colon carcinoma HT29 cellsEthanol : H2O (70 : 30)0.7 mg/mL50% growth inhibition similar to 500 nM of doxorubicin[119]
P.  vera Resin In vitro cytotoxic activity against human cell linesCrud methanolic extract fractionated against petroleum ether, chloroform,
and n-butanol
NDModerate 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 parametersP.  lentiscusLeaf 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]
Rat model using Thioacetamide Aqueous extract15 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 oilRabbit model, mercury induced toxicity Pistacia oil5% 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 FruitRabbit modelFruit1 g/kgInhibited the development of hydropic degeneration and fatty changes in the liver and demonstrated hypolipidemic effect [125]

Effects on atherosclerosisP.  vera Fruit Rabbit model Methanolic and cyclohexane extractsMethanolic 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 FruitRabbit modelFruit1 g/kgInhibited 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/mLRestored intracellular antioxidant glutathione (GSH) levels and downregulated CD36 mRNA expression resulted in antioxidant and antiatherogenic effects[126]

Anticholinesterase activityP.  atlantica leafTLC bioautography assay, Ellman’s colorimetric methodAqueous extract5, 10, 15, 20, and 25 µg/mLStrong acetylcholinesterase (AChE) inhibition[13]
P.  atlantica Leaf Ellman’s colorimetric methodMethanol and ethyl acetate extracts0.1 mg/mLRelatively weak AChE inhibitory activity[127]
P. terebinthus Fruit Ellman’s colorimetric method and the modified dopachrome method Ethyl acetate and methanol extracts25, 50, 100, and 200 µg/mLNo inhibitory activity against AChE and tyrosinase while selectively inhibited butyrylcholinesterase (BChE) at moderate levels (below 50%) at the tested concentrations[85]

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