Background Combretum paniculatum (Combretaceae) Vent. is commonly used in traditional medicine to treat ulcers and gastrointestinal disorders, including distended spleens and the liver. This study investigated the gastroprotective effects of C. paniculatum leaf extract and its fractions on absolute ethanol-induced gastric ulcers in rats and explored their effects on endogenous antioxidant (SOD, MDA, GSH, and Catalase) levels. Butanol, n-hexane, and ethyl acetate extracts (100 and 200 mg/kg), omeprazole (20 mg/kg), and control (3% Tween 80) were administered orally. Results The methanolic extract and fractions of C. paniculatum exhibited varying degrees of ulcer protection. MECP exhibited significant (P < 0.05) ulcer protection (55.56%) at 200 mg/kg; at 100 and 200 mg/kg, HFCP induced considerable (P < 0.01 & 0.001) ulcer reduction (64.44% and 80.00%), respectively; EAFCP offered substantial (P < 0.05) ulcer reduction (57.78%) at 200 mg/kg, whereas BFCP produced significant (P < 0.01) ulcer protection (73.33% and 68.89%) at 100 and 200 mg/kg against absolute ethanol-induced ulcer. MDA levels were substantially reduced after pretreatment with the extract and fractions, whereas SOD, GSH, and catalase levels were significantly enhanced. Conclusion These findings suggest that C. paniculatum leaf extract and fractions possess gastroprotective actions against ethanol-induced ulcers and exert these effects through antioxidant mechanisms. Therefore, the traditional use of C. paniculatum leaves in the treatment of ulcers is justified.
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