Danshensu Attenuates Apoptosis and Ferroptosis in Hypoxia Induced C2C12 Skeletal Muscle Cell Injury

Abstract

Exercise-induced muscle damage can be caused by excessive or unfamiliar eccentric exercises. Hypoxia induces oxidative stress in C2C12 myoblasts, mimicking intracellular muscle injury. Under hypoxic conditions, the accumulation of reactive oxygen species causes cell death through apoptosis and ferroptosis. Identifying candidate natural products involved in oxidative stress and developing strategies to mitigate these effects have garnered significant attention. In the present study, we used Danshensu as a candidate product to determine its protective effects against hypoxia-induced C2C12 cell damage via apoptosis and ferroptosis. The results showed that Danshensu restored cell death and apoptosis by regulating B-cell lymphoma 2 protein, its associated X Protein and cleaved-caspase 3. Additionally, Danshensu restored ferroptosis by regulating glutathione peroxidase 4 and solute carrier family 7 member 11 protein under hypoxic conditions. Moreover, the accumulation of reactive oxygen species caused by hypoxia was attenuated in the presence of Danshensu. These findings provide new insights into the potential of Danshensu as an alternative treatment for hypoxia-induced damage to the skeletal muscle C2C12 cell line.