Mechanistic insights into the anti-inflammatory activity of Pistachia lentiscus extract: A combined invivo, invitro, and insilico investigation

AbstractEthnopharmacological relevance: Pistacia lentiscus L., which is extensively distributed across the Mediterranean region, has long been employed in traditional medicine for the management of various ailments, mainly due to its reported anti-inflammatory, antimicrobial, and antioxidant properties. Despite evidence supporting its anti-inflammatory potential, comprehensive studies integrating biological experiments with computational approaches remain limited.Aim of the study: This paper focused on characterizing the anti-inflammatory potential of a hydro-methanol extract obtained from Pistacia lentiscus leaves collected in northeastern Algeria (Jijel region).To achieve this objective, a multidisciplinary strategy combining chemical profiling, experimental pharmacological assays, and computational modeling was employed in order to investigate both the biological efficacy of the extract and the molecular basis of its anti-inflammatory action.Materials and methods: The phytochemical profile of the extract was characterized using GC– MS analysis. Its anti-inflammatory efficacy was assessed in vivo using the carrageenan-induced paw edema model in rats. In vitro assays were conducted to evaluate erythrocyte membrane stabilization and protease inhibitory activity. Additionally, molecular docking studies were executed to investigate the binding interactions between the defined molecules and basic proteins acting in inflammation.Results: GC–MS analysis allowed the identification of 27 phytochemical constituents, among which shikimic acid was the most abundant (39.67%). Oral administration of the extract at 250 mg/kg produced a significant inhibition of paw edema (45.01%) after 120 minutes, surpassing the effect observed with the reference drug indomethacin (28.61%). In vitro experiments demonstrated a dose-dependent stabilization of erythrocyte membranes (41.42%) and pronounced protease inhibitory activity (82.43% at 50 µg/mL). Molecular docking results indicated that ethanone, 1-[4-methoxy-3-(4-methylphenoxy)phenyl]-, exhibited a high binding affinity toward inducible nitric oxide synthase (iNOS; PDB ID: 3E7G), with a predicted inhibition constant (Ki) of 0.128 µM, showing interaction patterns comparable to indomethacin.Conclusion: This study highlights the importance of natural anti-inflammatory agents as a promising source by presenting experimental and computational evidence supporting the potent anti-inflammatory potential of Pistacia lentiscus leaf extract.