Icariside II alleviates oxygen-glucose deprivation and reoxygenation-induced PC12 cell oxidative injury by activating Nrf2/SIRT3 signaling pathway

Cerebral ischemia-reperfusion (I/R) injury is a key contributing factor to the pathogenic mechanisms involved in ischemic stroke. The present study was designed to explore the effects of icariside II (ICS II) on oxygen-glucose deprivation/reoxygenation (OGD/R)-induced PC12 cell oxidative injury. The results showed that ICS II ameliorated OGD/R-induced PC12 cell injury at the concentrations of 12.5, 25, and 50 mu M, as evidenced by both the increase of cell viability and the decrease of LDH leakage from 33.96% +/- 0.48% to 16.78% +/- 0.78%, 13.12% +/- 0.17%, 12.96% +/- 0.10%, respectively. Moreover, ICS II not only attenuated the reactive oxygen species (ROS) from 212.2% +/- 5.45%, 168.6% +/- 5.29%, 148.7% +/- 9.37%, 142.7% +/- 7.76%, respectively, but also decreased the overproduction of mitochondrial ROS, as well as recovered the mitochondrial membrane potential (MMP) from 60.68% +/- 7.90% to 76.71% +/- 2.87%, 93.69% +/- 4.41%, 95.92% +/- 3.97%, respectively. Furthermore, OGD/R accelerated neuronal oxidative injury and apoptosis along with reduced nucleus-Nrf2, NQO-1, HO-1, Bcl-2 protein expressions, and increased Keap1, Bax and cleaved caspase-3 contents, whereas ICS II significantly reversed the abovementioned changes. Interestingly, ICS II also restrained the OGD/R-induced decrease in SIRT3 and IDH2 expressions. In conclusion, this study indicates that ICS II alleviates OGD/R-induced oxidative injury in PC12 cells, and its underlying mechanisms are due to the regulation of Nrf2/SIRT3 signaling pathway.