Schisandrin A prevents oxidative stress-induced DNA damage and apoptosis by attenuating ROS generation in C2C12 cells.

The generation of excessive reactive oxygen species (ROS) by oxidative stress has various deleterious effects on cellular constituents. Therefore, the discovery of natural products that can inhibit the production of ROS may be effective in suppressing the onset and treatment of oxidative stress-mediated diseases. Despite the antioxidant efficacy studies on various substances in the genus Schisandra used as traditional medicine, research on the efficacy of schisandrin A, a class of active lignans, remains insufficient. This study was conducted to evaluate the protective effect of schisandrin A on DNA damage and apoptosis induced by hydrogen peroxide (HO) in C2C12 cells. Results showed that schisandrin A effectively attenuated HO-induced cytotoxicity and DNA damage, which was related to the blockage of ROS accumulation. Schisandrin A also prevented the decrease in ATP content by HO and restored the HO-induced activation of AMP-activated protein kinase. In addition, schisandrin A prevented the release of HO-induced cytochrome c into the cytoplasm presumably by inhibiting the loss of mitochondrial membrane potential and the changes in the Bcl-2 family protein expression by HO. Furthermore, the blocking of HO-induced apoptosis by schisandrin A was associated with the inhibition of poly (ADP-ribose) polymerase degradation by the inactivation of caspase-3. These results suggest that schisandrin A maintains energy metabolism through the preservation of mitochondrial function while eliminating ROS generated by HO in C2C12 cells. Therefore, our data indicate that schisandrin A may have a beneficial effect on the prevention and treatment of diseases associated with apoptosis induced by oxidative stress.