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 μM, 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.