Effect of the main constituents of Pistacia lentiscus leaves against the DPPH radical and xanthine oxidase: experimental and theoretical study.

The aim of this work is to study the content of phenolic compounds in leaves and their antioxidant effect. After extracting the phenolic compounds, fractionation by liquid/liquid partition with increasing polarity gives five extracts. Three of them (ButF, AqF and ButA) were found to have good antioxidant activity. Their IC for the inhibition of the free radical formation of DPPH are 1.76µg/mL, 1.307µg/ml, and 1.77µg/mL, respectively. These values are very interesting, considering the effect of the powerful flavonoid quercetin, whose IC against DPPH is 1.53µg/mL. These extracts are also active against xanthine oxidase (XO). The IC measured are 0.14mg/mL, 0.186mg/mL and 0.33mg/mL for ButF, Aq F and ButAq F extract respectively, in comparison with allopurinol (0.44mg/mL). A phytochemical analysis by LC/ESI-MS-MS was performed to explain the observed activities. The results show 22 peaks representing: flavanols, namely catechin, d-Gallocatechin, and gallocatechin gallate. The only flavone detected in the studied extracts was luteolin glucuronide and was found to be in higher amounts in butanolic extract (2,71mg/mL). The phenolic acids and derivatives were also identified in the extracts. A theoretical study was performed to deduce the specificity of the binding between the major compounds identified in the extract and the xanthine oxidase enzyme using Schrödinger software. The docking procedure was validated using the extraction of ligands from the binding site. Their re-anchoring to the xanthine oxidase structure using quercetin and allopurinol was considered reference molecules. After docking, post-docking minimization was performed to achieve the best scoring poses with the MM-GBSA approach. The dGBind energy of MM-GBSA representing the binding energy of the receptor and the ligand was calculated based on molecular mechanics. Results reveal that β-Glucogallin compounds such as Digalloylquinic acid, Gallocatechin, and Myricetin-3-O rhamnoside are more active than allopurinol, with stronger Docking score (Gscore) and MM-GBSA dGBind.Communicated by Ramaswamy H. Sarma.