Neuroprotective effect of ginkgolide K against H₂O₂-induced PC12 cell cytotoxicity by ameliorating mitochondrial dysfunction and oxidative stress

抄録

Mitochondria and oxidative stress play important roles in neuronal cell death associated with cerebral ischemia. Elevated level of reactive oxygen species (ROS) and mitochondrial dysfunction are thought to be responsible for cerebral ischemia injury along with neural cells death through several apoptotic mechanisms. In this study, exposure of rat pheochromocytoma (PC12) cells to hydrogen peroxide (H₂O₂) at the concentration of 0.3 mM for 24 hour caused significant loss of cell viability, LDH release from cells, ascent of ROS level and mitochondrial membrane potential (MMP) decrease. Moreover, the activities of caspase-9, caspase-8 and caspase-3 all were increased in H₂O₂-induced PC 12 cells. However, pretreatment with ginkgolide K (GK) solutions of different concentrations (10, 50, 100 μM) for 24 h prior to exposuring to H₂O₂ significantly increased cells viability, suppressed LDH release, attenuated ROS level, prevented cytochrome c release from mitochondria and boosted MMP expression. In addition, ginkgolide K notably inhibited the caspase-3 and caspase-9 but not caspase-8 activities in exogenous H₂O₂-treated PC12 cells. These results demonstrated that ginkgolide K protected PC12 cells from H₂O₂-induced apoptosis by restoring MMP expression, ameliorating oxidative stress and subsequently leading to inhibit the activity of caspase-3 protein. Therefore, the present study supported that ginkgolide K may be a promising neuroprotective compound for cerebral ischemia treatment.