Gastroprotective effect of gallic acid against ethanol-induced gastric ulcer in rats: Involvement of the Nrf2/HO-1 signaling and anti-apoptosis role

• Gallic acid (GA) showed protective effects against ethanol-induced gastric ulcer in rats. • The gastroprotective effect of GA could be partly related to the stimulations of gastric nitric oxide and prostaglandin. • Nrf2/HO-1 signaling activation is involved in the protection of GA against ethanol-induced gastric mucosa injury. • Pretreatment with GA could inhibit the apoptosis of gastric mucosal cells. Gallic acid (3,4,5-trihydroxybenzoic acid, GA) is a phenolic compound found in many medicinal plants traditionally used in China or patent medicine such as Feiyangchangweiyan capsule (FY capsule) for the treatment of gastrointestinal diseases for decades. However, the evidence for the gastroprotective effect of GA is deficient and the pharmacological mechanisms remain limited. The present investigation was initiated to demonstrate the gastroprotective effect and to understand potential underlying mechanism of GA on ethanol-induced gastric ulcer in rats. Gastric ulcers were induced by absolute ethanol (5 mL/kg, i.g.) in male Sprague-Dawley rats, GA (10, 30, and 50 mg/kg), FY capsule (0.4 g/kg) and 30 mg/kg Lansoprazole was administered orally. Physiological saline and lansoprazole were used as negative and positive control, respectively. Induction of rats with ethanol resulted in a significant rise in ulcer index, serum levels of inflammatory cytokines markers (IL-1β, IL-6 and TNF-α), TBARS, protein expression of Bax and Caspase-3 and a significant reduction in the activities or levels of endogenous antioxidants (SOD, CAT and GSH), gastric mucosal protective factors (PGE2 and NO) and protein expression of Bcl-2. Pretreatment with GA showed a remarkable decrease in ulcer index, inflammatory cytokines markers, TBARS, protein expression of Bax and Caspase-3 and a significant increase in the activities of endogenous antioxidants, levels of PGE2 and NO, and protein expression of Bcl-2, Nrf2 and HO-1 when compared with ethanol treated groups. This study demonstrated the gastroprotective effect of Gallic acid and FY capsule on ethanol-induced gastric ulcer in rats. The underlying mechanism of GA and FY capsule against gastric ulcer in rats caused by ethanol might be involved in Nrf2/HO-1 anti-oxidative pathway and ultimately played an anti-apoptotic role through regulating Bax, Bcl-2 and Caspase-3.