The preventive effect of Mori Ramulus on oxidative stress-induced cellular damage in skeletal L6 myoblasts through Nrf2-mediated activation of HO-1.

The aim of the present study is to investigate the preventive effect of water extract of Mori Ramulus (MRWE) on oxidative stress-mediated cellular damages in rat skeletal L6 myoblasts. Our results demonstrated that MRWE pretreatment markedly improved cell survival and suppressed cell cycle arrest at the G2/M phase and apoptosis in hydrogen peroxide (H₂O₂)-treated L6 cells. H₂O₂-triggered DNA damage was also notably reduced by MRWE, which since it was correlated with protection of reactive oxygen species (ROS) production. Additionally, H₂O₂ stimulated cytosolic release of cytochrome c and up-regulation of Bax/Bcl-2 ratio, whereas MRWE suppressed these changes following by H₂O₂. Moreover, MRWE inhibited the cleavage of poly(ADP-ribose) polymerase as well as the activity of caspase-3 by H₂O₂. Furthermore, MRWE enhanced H₂O₂-mediated expression of nuclear factor erythroid 2-associated factor 2 (Nrf2) and its representative downstream enzyme, heme oxygenase-1 (HO-1). However, the protective effects of MRWE on H₂O₂-induced ROS production, cell cycle arrest and apoptosis were significantly attenuated by HO-1 inhibitor. In conclusion, our present results suggests that MRWE could protect L6 myoblasts from H₂O₂-induced cellular injury by inhibiting ROS generation along with Nrf2-mediated activation of HO-1, indicating this finding may expand the scope of application of Mori Ramulus in medicine.