Schisandrin C enhances mitochondrial biogenesis and autophagy in C2C12 skeletal muscle cells: potential involvement of anti-oxidative mechanisms

The molecular study of muscles is needed to overcome chronic inflammation and maintenance of muscles in the human body. Schisandrin C is a pharmacological compound derived from the fruit of Schisandra chinensis and has many characteristics including anti-inflammation, anti-tumor, and anti-oxidation. However, the cellular and molecular mechanisms of Schisandrin C are still not well understood especially in skeletal muscle. Therefore, the present study was evaluated whether the properties of Schisandrin C in C2C12 skeletal muscle cells involved maintenance of cellular homeostasis and protection against oxidative damage. Differentiated C2C12 cells were exposed to H₂O₂ to induce oxidative stress. The characteristics of anti-oxidants, anti-inflammation, autophagy, and mitochondrial biogenesis were tested by Western blotting. Confocal microscopy was also used to observe mitochondrial activity. Schisandrin C inhibited inflammatory molecules with enhancing anti-oxidant activity and reducing reactive oxygen species (ROS) even in the presence of H₂O₂. The dual anti-inflammation and anti-oxidant roles of Schisandrin C regulated the translocation of nuclear factor kappa B (NF-κB) and nuclear factor erythroid 2-related factor-2 (Nrf-2) to nucleus followed by inhibition of the mitogen-activated protein kinase (MAPK) pathway. Schisandrin C promoted the expression of autophagy and mitochondrial biogenesis molecules. Furthermore, the effect of Schisandrin C increased the mitochondrial activity against oxidative stress. Consequently, the action of Schisandrin C enhanced the regulation of autophagy and mitochondrial biogenesis with potential involvement of anti-oxidative mechanisms including the MAPKs/Nrf-2/heme oxygenase-1 signaling pathway in C2C12 skeletal muscle cells exposed to oxidative stress. Therefore, Schisandrin C may be considered as a beneficial compound for several muscle inflammations.