Different methods were used to evaluate the antioxidant capacity of phenolic extracts of P. lentiscus: DPPH (2,2-diphenyl1-picrylhydrazyl), i.e., free radical scavenging activity; free hydroxyl radicals (HO); ferric-reducing power (FRAP); the carotene bleaching (CB) assay; the oxygen radical absorbance capacity (ORAC) test; hydrogen peroxide scavenging activity (H₂O₂); the phosphomolybdenum (TAC) assay; and the ABTS·+: 2,2′-azino-bis-(3 ethylbenzthiazoline-6-sulphonic acid) assay were the most used (Table 13). These methods have different modes of action. Electron transfer, proton transfer, and iron reduction are the main mechanisms involved. The observations noted after the evaluation of the antioxidant potential of this plant are illustrated in Table 13. Investigations (Table 13) were conducted regarding the evaluation of antioxidant activity by comparing to reference antioxidants (ascorbic acid, gallic acid, trolox, rutin, and quercetin). The results of these investigations revealed that lentisk’s antioxidant properties are comparable to those of the reference antioxidants. The extracts of P. lentiscus remain a considerable source of natural antioxidants.

The ability of the P. lentiscus extracts to prevent free radicals could be attributed to the high content of phenolic compounds ^[1][2][3][4][23,29,30,34]. There is a significant positive correlation between the antioxidant test results and the amount of total phenols ^[5][37]. The antioxidant capacity of P. lentiscus extract has been shown to be due primarily to gallic acids and their galloyl derivatives (5-Ogalloyl; 3,5-O-digalloyl; 3,4,5-tri-O-galloyl) ^[1][23]. The trapping of DPPH increases accordingly with the number of galloyl groups ^[1][23]. Quercetin and gallic acid are powerful natural antioxidants ^[1][23], and monophenols are less effective than polyphenols ^[6][7][61,62]. With gallic acid, the inductive effect of these three hydroxyl groups is a significant factor influencing the increase in antioxidant activity ^[6][61]. This suggests that they are partly responsible for the antiradical potential observed in the lentisk extracts ^[8][43]. In addition, the antioxidant activity also depends on the polarity of the solvent, the solubility of the phenolic compounds, and the hydrophobic nature of the reaction medium ^[9][42]. A high polarity of the extract solvent increases the antioxidant capacity (DPPH and FRAP) of the lentisk extracts. Polar extracts such as ethanol, methanol, and aqueous extracts were found to be rich in polar compounds, which are either hydrogen atom donors or singular atom transfer agents ^[9][42]. In addition to the solvent polarity, the solubility of the phenolic compounds is governed by the degree of polymerization of the phenols, the part of the plant used, and the variability of soil and climatic conditions ^[10][11][63,64]. The flavonol glycosides found in lentisk ^[8][12][13][1,43,57] are known for their antioxidant attributes, which are strongly related to their structural characteristics, i.e., the hydrogen donor substituents (OH groups) and the presence of a 2,3 double bond that increases their scavenging capacity and inhibition of pro-oxidant enzymes ^[14][24]. It has been shown that the main compound present in lentisk extracts, i.e., myricetin-rhamnoside ^[8][12][1,43], has a DPPH scavenging capacity comparable to that of vitamin C ^[15][65].

Researchers evaluated the antimicrobial and antifungal activities of lentisk phenolic extracts (Table 13). The evaluation of the antimicrobial activity was based on the comparison of the antimicrobial effects of lentisk extracts and those of the different antibiotics (such as amphotericin, amoxicillin, and ciprofloxacin) used in the studies presented in Table 13. The results of these studies revealed that the extracts from leaves show an interesting antimicrobial potential against Gram-positive and Gram-negative bacteria, but also against different fungi. The disk diffusion method and/or the dilution method were the most useful methods. Lentisk leaf extracts prepared in different solvents (dichlotomethane, methanol, ethanol, ethyl acetate, and water) were all found to be effective against the bacteria Micrococcus luteus, Bacillus subtilis, Listeria innocua, and Escherichia coli ^[9][42]. The same extracts also have an inhibiting effect against fungal strains as Candida pelliculosa and Fusarium oxysporum albidini ^[9][42]. Lauk et al. (1996) ^[24][68] showed that lentisk leaf decoctions have good antibacterial activity against Sarcina lutea, Staphylococcus aureus, and Escherichia coli (with MIC = 312 mg/L for the three bacteria tested). The activity against fungal cells, Candida albicans, Candida parapsilosis, Torulopsis glabrata, and Cryptococcus neoformans seems to be much more interesting ^[11][64]. Bakli et al. (2020) ^[4][34] showed that the ethyl acetate fraction from an ethanolic leaf extract had remarkable activity against V. cholerae with a value of MBC 0.3 mg/mL ^[4][34]. Another study showed that methanol extracts had a significant inhibitory effect on the growth of bacterial isolates (Staphylococcus aureus, Staphylococcus haemolyticus, Pseudomonas aeruginosa, and Proteus mirabilis). This methanolic extract showed a higher zone of inhibition than that of the aqueous extract. The maximum zone of inhibition was observed in the methanolic extract at 100% concentration with 33 mm and 27 mm against S. aureus and S. haemolyticus, respectively ^[25][69]. P. aeruginosa was of particular interest, as this bacterium was inhibited by the methanol extract to a greater extent than with the use of the reference antibiotic levofloxacin ^[25][69]. In most of these studies, Gram-negative bacteria were found to be less sensitive to the extracts than Gram-positive bacteria.

This can be explained due to the presence of hydrophobic lipopolysaccharides in the outer membrane, which provide protection against different agents ^[34][72], in addition to enzymes in the periplasm that destroy foreign molecules introduced from the outside ^[35][73]. The antimicrobial activity observed in this study could be due to the presence of flavonoid compounds (kaempferol, myricetin, quercetin, and rutin) in the lentisk extracts. Flavonoids are known for their antimicrobial activity against a wide range of microorganisms ^[4][34]. They have multiple cellular targets and can be applied to different components and functions in the bacterial cell ^[36][37][74,75]. These kinds of molecules promote antimicrobial activity against human pathogenic microorganisms ^[38][76].

Some studies (Table 13) aimed to evaluate the anticancer potential of different phenolic extracts of this plant in vitro. The ethanolic leaf extracts showed anticancer potential against lung cancer A549, breast cancer MCF7, prostate cancer PC3, and HepG2 liver cancer in vitro ^[27][45]. Yemmen et al. (2017) ^[29][60] revealed the anti-proliferative activities of leaf hydro-methanolic extracts against two human neuroblastoma cell lines (SK-N-BE(2) C and SH-SY5Y) with IC50 values of 100 μg/mL and 56 μg/mL, respectively. The anticancer potential of the crude extracts against melanoma (B16F10) and breast (EMT6) cell lines was also evaluated. The leaf and fruit extracts inhibited the growth of B16F10 cells (IC50 = 56 and 58 μg/mL, respectively) ^[9][42].

Phytochemical studies have indicated the presence of significant amounts of flavonoids, tannins, and phenolic compounds in P. lentiscus extracts ^[14][24], which may be responsible for the anticancer activity of lentisk extracts. It has been shown that the presence of a 2,3-double bond and three adjacent hydroxyl groups in the structure could confer a higher anticancer potential to a flavonoid ^[39][77]. One example of the flavnoids found in lentisk extracts is myricetin; this molecule was found to have significant cytotoxic activity against B16F10 melanoma cell cultures ^[39][77].

P. lentiscus is used in traditional medicine for the treatment of inflammation, burns, and gastrointestinal disorders. Anti-inflammatory activity has been the focus of many recent investigations (Table 13). Dellai et al. (2013) ^[31][71] examined the efficacy of aqueous and organic extracts of P. lentiscus leaves in vivo for their anti-inflammatory and anti-ulcerogenic activities using the carrageenan-induced paw edema assay and HCl/ethanol-induced gastric injury in rats, respectively. Aqueous (AQ), chloroformic (CHCl₃), ethyl acetate (EtOAc), and methanolic (MeOH) leaf extracts administered intraperitoneally showed a dose-dependent anti-inflammatory effect. Leaf extracts of CHCl₃, EtOAc, and MeOH, administered orally, showed concentration-dependent inhibition of gastric lesions. The effect of all the extracts in both activities is comparable to the reference drugs: cimetidine and acetylsalicylate of lysine, respectively ^[31][71]. The pharmacological evaluation of the P. lentiscus leaf extracts showed the anti-inflammatory potential of this plant and that its activity is unlike non-steroidal anti-inflammatory drugs and corticosteroids. The extracts did not cause damage to the stomach mucosa but showed an inhibition of lesion formation. The work carried out by Bouriche et al. (2016) ^[32][31] concerns the measurement of the anti-inflammatory activity of alcoholic and aqueous extracts of P. lentiscus leaves. Croton oil-induced ear edema in mice was used as a model of acute inflammation. The results showed that a local treatment with 2 mg/ear of alcoholic extract significantly decreased ear edema (65%), while the aqueous extract exerted a weaker inhibitory effect (51%). The anti-inflammatory activity of lentisk was otherwise examined by measuring the secretion of interleukin-1β by macrophages exposed to ATP or H₂O₂. The leaf extract (100 μg/mL) showed significant anti-inflammatory activity compared to acetylsalicylic acid (ASA) ^[32][31].

The mechanism of action of indomethacin on inflammation is based on the inhibition of pro-inflammatory prostaglandin synthesis ^[40][79]. The anti-inflammatory effect of the acetone extract of P. lentiscus fruit is probably attributed to the lipophilic soluble substances that are able to penetrate through the skin barrier ^[41][80] and can thereby exert their anti-inflammatory effects. Likely candidates for these anti-inflammatory substances are flavonoids and polyphenols, which have been isolated from P. lentiscus. Phenolic compounds are known to interact with and penetrate through lipid bilayers ^[42][81]. The observed anti-inflammatory effect is also likely due to the presence of antioxidant compounds in the extract.

The anti-inflammatory results ^{[8][30][31][32][33]}[25,31,43,46,71] provide valuable evidence regarding the anti-inflammatory potential of P. lentiscus leaves, suggesting that this plant can be exploited as a natural source of anti-inflammatory agents.

The results obtained in all the studies illustrated above indicate that the extracts of P. lentiscus present antioxidant, anti-inflammatory, anticancer, and antimicrobial properties in agreement with the traditional uses of the plant.