Gastroprotective Effect of Punicalagin against Ethanol-Induced Gastric Ulcer: The Possible Underlying Mechanisms

Gastric ulcer is the most digestive disease found in clinical practice. Punicalagin (PCG) found in pomegranate juice has antioxidant and tissue repair properties. Therefore, the aim of this study was to investigate punicalagin’s gastroprotective effect against ethanol-induce gastric injury. Four groups of rats; first group served as control, group 2: Treated with absolute ethanol (5 ml/kg, po), group 3: Rats were pre-treated with ranitidine (as a reference drug) (50 mg/kg, po) before ethanol and group 4: Pre-treated with PCG (4 mg/kg, po) before ethanol. Pretreatment with PCG reduced ulcer index and histopathological changes, oxidative stress induced by ethanol while it elevated antioxidant activity. Although, it down regulated Tumor Necrosis Factor (TNF-α) gene expression and mucosal levels of inflammatory cytokines; TNF-α, Interleukin (IL-1β) and Interferon Gamma (IFNγ), it up regulated mucosal level of IL-10. Also, it reduced mucosal Nuclear Factor Kappa B (NFκB) protein expression, mylopeoxidase and caspase 3 activities as well as gene expression of caspase 9 while it elevated antiapoptotic B-Cell Lymphoma 2 (Bcl-2) gene expression, mucosal nitric oxide and mucin content. However, it had negative action on prostaglandin E2 and acid secretions. These findings indicate gastroprotective effects of punicalagin against ethanol induced gastric ulcer through suppression of mucosal oxidative stress and inflammation through NFκB pathway as well cytoprotective defences independent on prostaglandin E2 and acid secretions.