Gastroprotective effect of 8-alkylberberine derivatives on ethanol-induced gastric ulcer in rats

Abstract

Berberine (BBR) is an isoquinoline alkaloid which protects the acute gastroenteritis and inhibits gastric ulcers, and 8-Alkylberberine (8-BBR-Cn, n=4, 8, 12 and 16) with a long aliphatic chain are synthesized have been reported. This paper investigated the possible mechanisms underlying the gastroprotective effect of 8-BBR-Cn derivatives at dose of 25, 50 and 100 mg/kg body weight on enthanol-induced gastric mucosal injury in rats. The ulcer index and percentage inhibition were evaluated. The stomachs tissues were chosen for determination of nitric oxide synthase (NOS) activity and prostaglandin E2 (PEG2) levels, and assay kit were used for the above two assays. Compared with model control group, the ulcer indexes of 8-BBR-Cn (25, 50 and 100 mg/kg, i.g.) treatment groups decreased significantly. Additionally, 8-BBR-Cn could enhance PEG2 concentration in mucosal tissue of gastric ulcer rats. Moreover, in mucosal tissue, activities of total NOS (TNOS) and constitutive NOS (cNOS) were increased, but inducible NOS (iNOS) was decreased by 8-BBR-Cn. 8-BBR-Cn derivatives had protective effect on gastric mucous membrane, and 8-BBR-C16 displayed stronger gastroprotective effect as carbon chain at C8 position lengthens, which was related to prostaglandin E2 and nitric oxide synthase pathways.