Activation of the Nrf2/HO-1 signaling pathway contributes to the protective effects of platycodin D against oxidative stress-induced DNA damage and apoptosis in C2C12 myoblasts.

Abstract

Myoblast damage by oxidative stress has been proposed as one of the main causes of skeletal muscle loss due to induction of muscle damage. Platycodin D, a triterpenoid saponin found in the root of Platycodon grandiflorum (Jacq.) A. DC., has been known to possess strong antioxidant activity. However, whether platycodin D can defend myoblasts against oxidative injury remains to be elucidated. Therefore, this study was conducted to investigate the potential protective effects of platycodin D against oxidative stress in mouse myoblast C2C12 cells. The results demonstrated that platycodin D inhibited hydrogen peroxide (H2O2)-induced cytotoxicity and DNA damage by blocking abnormal reactive oxygen species (ROS) generation. Furthermore, platycodin D protected cells from the induction of mitochondria-mediated apoptosis by oxidative stress. In addition, platycodin D markedly promoted the activation of nuclear factor-erythroid-2-related factor 2 (Nrf2), which was associated with the enhanced expression of heme oxygenase-1 (HO-1) in the presence of H2O2. However, inhibiting the expression of HO-1 by Nrf2 siRNA significantly attenuated the protective effect of platycodin D, indicating that platycodin D activates the Nrf2/HO-1 signaling pathway to protect against oxidative stress. Based on current data, platycodin D may be useful as a potential therapeutic agent against various oxidative stress-related muscle disorders.