Thesis (M.Sc. in Pharm.)--Chulalongkorn University, 2002

Bergenin is a compound isolated from several plants used in folk medicine in many Asian countries. In this study, effects of bergenin on cultured rat cerebellar granule cells and on glutamate-induced neurotoxicity in these cells were investigated by using cell viabillity, lipid peroxidation and glutathione content, as the measuring endpoints. Eight-day cultured cerebellar granule cells were used in all experiments. In preliminary experiment, cultured cells were exposed to bergenin (10-100 micrometre) for different time intervals. The results showed that mitochondrial function of cells exposed to bergenin (100 micrometre) for 48 hr was decreased. To study effects of bergenin on glutamate-induced neurotoxicity on cultured cerebellar granule cells, experiments were divided into two parts. The first part was performed by preexposing cerebellar granule cells to different concentrations of bergenin for 48 hr, then replaced by 500 micrometre glutamate for 8 hr. The second part was performed by coexposing cultured cells to bergenin (10-100 micrometre) and 500 micrometre glutamate for 8 hr. Experimental results showed that both preexposure and coexposure with bergenin did not prevent glutamate-induced neurotoxicity in cultured cerebellar granule cells. Instead, bergenin tended to aggravate cytotoxicity of glutamate by intensifying the suppression of mitochondrial function. However, there was no statistically significant difference among glutamate-treated alone or preexposure or coexposure to bergenin groups. Bergenin did not alter cellular lipid peroxidation levels but might exert marginal, although statistically nonsignificant, restorative effects on glutamate-induced glutathione diminution in both preexposure and coexposure experiments. In conclusion, bergenin decreased mitochondrial activity of cultured cerebellar granule neurons at high concentrations while at lower concentrations did not showed any beneficial effects on glutamate-induced neurotoxicity in cultured rat cerebellar granule cells. It was notable that bergenin showed a tendency to intensify glutamate-induced neurotoxicity, although the difference was not statistically significant. This tentative adverse effect of bergenin and its mechanism of action on cultured neurons are still unclear at the present time