Oyster polysaccharide alleviates TNF-α-induced muscle atrophy via regulation of the calcium signalling pathway in C2C12 myoblasts.

This study aimed to elucidate how Crassostrea hongkongensis polysaccharide (CHP) alleviates TNF-α-induced atrophy in C2C12 myotubes. CHP enhances MyHC expression while suppressing the muscle atrophy markers MuRF1 and MaFbx. Additionally, CHP significantly enhanced mitochondria biogenesis and ATP production. This effect may be attributed to CHP induced activation of glucagon and glycolysis/gluconeogenesis signalling pathways, as well as its modulation of insulin resistance. Transcriptomic analyses demonstrated that CHP attenuated the TNF-α mediated inhibition of C2C12 myoblast differentiation and multinucleated myotubes formation, potentially through modulation of calcium signalling pathways. Molecular docking, molecular dynamics, and quantum chemical assessments suggest that the branched structure of CHP molecules promotes flexible electron distribution. This stabilizes the binding of CHP to sarco/endoplasmic reticulum calcium ATPase (SERCA), which is crucial for calcium reuptake. Consequently, CHP upregulates energy metabolism pathways to improve mitochondrial function, increases the SERCA expression to promote calcium reuptake, thereby alleviating muscle waste.