Neuro2a Cell Death Induced by 6-Hydroxydopamine is Attenuated by Genipin

We have previously reported that genipin, a natural iridoid compound, shows neuritogenic activity in cultured rat pheochromocytoma PC12h and mouse neuroblastoma Neuro2a cells. 6-Hydroxydopamine (6-OHDA) is a dopaminergic neurotoxin putatively involved in the pathogenesis of Parkinson's disease (PD). Here, we studied the protective effects of genipin on 6-OHDA-induced cytotoxicity in Neuro2a cells. 6-OHDA treatment markedly reduced Neuro2a cell viability in a concentration-dependent manner causing DNA condensation and fragmentation. Genipin significantly protected the cells against the 6-OHDA-induced cytotoxicity. Genipin also protected the cells against hydrogen peroxide (H2O2)-induced cytotoxicity. It is known that 6-OHDA is rapidly and non-enzymatically oxidized by molecular oxygen to form H2O2 and the corresponding p-quinone. These data suggest that genipin is effective at protecting against neurodegeneration that involves oxidative stress, such as PD.