6,7-di-O-glucopyranosyl-esculetin protects SH-SY5Y cells from dopamine-induced cytotoxicity.

Dopamine, as a neurotoxin, can elicit severe Parkinson's disease-like syndrome by elevating intracellular reactive oxygen species levels and apoptotic activity. In this study, we examined the effect of 6,7-di-O-glucopyranosyl-esculetin, which was extracted from Fraxinus sieboldiana bloom, on dopamine-induced cytotoxicity and the underlying mechanism in human neuroblastoma SH-SY5Y cells. Our results suggest that the protective effects of 6,7-di-O-glucopyranosyl-esculetin (0.1, 1 and 10 microM) on dopamine-induced cytotoxicity may be ascribed to its anti-oxidative properties by reducing reactive oxygen species levels, and its anti-apoptotic effect via protecting mitochondrion membrane potential (Delta Psi m), enhancing superoxide dismutaese (SOD) activity and reduced glutathione (GSH) levels, and regulating p53, Bax and Bcl-2 expression. In addition, 6,7-di-O-glucopyranosyl-esculetin inhibited the release of cytochrome c and apoptosis-inducing factor (AIF), and the protein expression of activated caspase 3. These data indicate that 6,7-di-O-glucopyranosyl-esculetin may provide a useful therapeutic strategy for the treatment of progressive neurodegenerative diseases such as Parkinson's disease.