Gastroprotective activity of a new semi-synthetic solidagenone derivative in mice

Abstract

The gastroprotective activity of the new semi-synthetic solidagenone derivative 15,16-epoxy-8(9),13(16),14-labdatrien-7beta-methoxy-6beta-ol (ELMO) has been assessed on the model of HCl/EtOH-induced gastric lesions in mice. Human gastric epithelial cells (AGS) and fibroblasts (MRC-5) were used to determine its mode of action. The effect of ELMO on the prostaglandin E-2 content, cellular reduced glutathione (GSH) and protection against damage induced by sodium taurocholate was assessed against AGS cells. The effect of ELMO on the growth of AGS and fibroblast cultures was evaluated. The superoxide anion scavenging capacity of the compound was studied also. The cytotoxicity of ELMO, expressed as cell viability, was assessed using two independent endpoints: neutral red uptake (NRU) and the reduction of 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) for MRC-5 fibroblasts and NRU for AGS cells. A single oral dose of ELMO (10 and 20 mg kg(-1)) inhibited the appearance of gastric lesions in mice displaying similar values to lansoprazole at 20 mg kg(-1). At 40 muM ELMO increased the prostaglandin E-2 content but not GSH in AGS cells. The compound showed no effect on sodium taurocholate-induced damage and was devoid of superoxide anion scavenging activity. Concentrations of 0.5, 1, 2 and 4 muM stimulated fibroblast but not AGS cell proliferation. The compound showed weak cytotoxicity with values (IC50) of 411 (NRU) and 418 muM (MTT) for fibroblasts and 261 muM (NRU) for AGS cells. The results support further pharmacological study of this compound as a potential new anti-ulcerogenic drug.