Gastroprotective effects of ursolic acid isolated from Ochrosia elliptica on ethanol-induced gastric ulcer in rats

The prevention of gastric ulcer pathogenesis or its recurrence is currently one of the main goals of clinical and experimental studies. This study was conducted to investigate the gastroprotective effects of ursolic acid (UA) isolated from the dichloromethane/methanol extract of shoots of Ochrosia elliptica Labill. and investigated for its activity against an ethanol-induced gastric ulcer model in rats. Fifty-six female albino rats were divided into seven groups (eight rats per group): The first group served as control; group 2: absolute ethanol group (5 ml/kg. b.w.); group 3: ranitidine pretreated group (50 mg/kg, i.p.); group 4: UA (100 mg/kg, b.w.); and groups from 5 to 7 were pretreated with UA (25, 50, and 100 mg/kg, b.w.). Then, all animals were sacrificed, and the stomachs were excised for examination. Gastric mucosal injuries were assessed by gross examination, histopathology, immunohistochemistry of caspase-3, and biochemical parameters, including tissue malondialdehyde (MDA) and total antioxidant capacity (TAC) levels. The ethanol group showed severe mucosal injury compared with UA-treated animals, which grossly showed significant reductions of ulcer areas. Histopathologically, they showed marked reductions of mucosal necrosis, edema, and leukocyte infiltrations. Significant increased TAC levels were associated with reduced MDA levels UA-treated rats. In addition, the caspase-3 activity was downregulated. These findings indicated gastroprotective effects of UA at the administered doses comparable with that observed with the control drug ranitidine through suppression of mucosal oxidative stress and antiapoptotic activities. Molecular docking studies showed that UA binds to H+/K+ ATPase more than omeprazole and ranitidine -9.23 vs. -7.09 and 6.29 kcal/mol). In addition, the pKi value of UA was also lower than omeprazole and ranitidine (169.6 nM vs. 6.3 and 26.7 mu M). The molecular docking findings suggested the protection role of UA against ethanol-induced gastric ulcer.