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

Year: 0

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.

Publisher: Institute of Molecular Physiology and Genetics SAS