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

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 h caused significant loss of cell viability, lactate dehydrogenase (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 PC12 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.