Evaluation of the gastroprotective mechanisms of the ethanol leaves extract of Jatropha multifida in ethanol-induced gastric ulceration in Wistar rats: Integrated in Vivo, biochemical, and in silico study

Abstract

Peptic ulcer disease (PUD) results from an imbalance between aggressive factors and mucosal defense mechanisms, with oxidative stress and prostaglandin depletion playing central roles in peptic ulcerations. This study investigated the gastroprotective potential and mechanistic pathways of the ethanol extract of Jatropha multifida leaves using integrated phytochemical, in Vivo, biochemical, and in silico approaches. Twenty-eight male Wistar rats were randomly assigned to seven groups (n = 4). Gastric ulceration was induced using 96% absolute ethanol. Ulcer index (UI), preventive ratio (PR), malondialdehyde (MDA), oxidative stress (SOD, Catalase); prostaglandin levels, hematological indices, and histopathology were assessed. Phytochemical profiling and GC-MS characterization were performed. Molecular docking against COX-2 was conducted using AutoDock Vina. Significant levels were determined at (p < 0.05). Ethanol significantly increased the ulcer index (p < 0.05). Pretreatment with extract reduced UI dose-dependently at 100, 300, and 500 mg/kg b.w, respectively (p < 0.05 vs positive control). MDA levels, SOD and catalase significantly increased (p < 0.05), while SOD and catalase activities increased dose-dependently compared to the induced not treated group. Prostaglandin levels were significantly restored in extract-treated groups compared to the induced, not treated group (p < 0.05). Hematological parameters showed stabilization at high doses. GC-MS identified phytol (21.67%) and neophytadiene (12.34%) as major constituents. Molecular docking revealed a strong binding affinity of 5,7,8-trimethyltocol to COX-2 (−7.2 kcal/mol), exceeding ranitidine (−5.5 kcal/mol) standard. In conclusion, J. multifida leaf extract confers significant, dose-dependent gastroprotection via antioxidant enhancement, prostaglandin restoration, inflammatory modulation, and COX-2 interaction, supporting its translational phytotherapeutic potential.