Astragaloside IV rescues MPP+-induced mitochondrial dysfunction through upregulation of methionine sulfoxide reductase A.

Methionine sulfoxide reductase (Msr) repairs oxidatively damaged proteins through acting as an antioxidant. Oxidative stress has been postulated to cause the mitochondrial dysfunction that is associated with aging and certain diseases, including Parkinson's disease (PD). The present study investigated the protective effects of astragaloside IV (AS-IV) on 1-methyl-4-phenylpyridinium (MPP+)-induced mitochondrial dysfunction through MsrA in PC12 cells. This revealed that oxidative stress reduced the expression of MsrA following MPP+ treatment. AS-IV was demonstrated to protect PC12 cells from MPP+-induced oxidative damage through upregulating MsrA. MsrA expression was dependent on the Sirt1-FOXO3a signaling pathway. In addition, knockdown of MsrA reduced the protective effects of AS-IV, indicating that the antioxidant effects of AS-UV occurred through MsrA. These results suggest that AS-IV exerts antioxidant effects and regulates mitochondrial function. Thus, AS-IV may serve as an effective therapeutic agent for aging and PD.