Protective Effects of Momordica charantia Extract on Dexamethasone-Induced Sarcopenic Changes in C2C12 Cells:...

Background/Objectives: Sarcopenia is characterized by progressive skeletal muscle loss and impaired myogenic differentiation and is closely associated with inflammation and metabolic dysfunction. Methods: This study investigated the protective effects of Momordica charantia extract against dexamethasone-induced sarcopenia and explored the underlying mechanisms using network pharmacology, C2C12 cell-based assays, Western blotting, and molecular docking. Network pharmacology analysis identified quercetin, ascorbic acid, and tocopherol as major active compounds associated with targets related to inflammation, extracellular remodeling, and metabolic dysfunction. Results: M. charantia extract (MCE) did not markedly reduce cell viability at concentrations up to 100 μg/mL and improved dexamethasone-induced morphological impairment of myotubes. The extract reduced MAFbx, MMP-2, and MMP-9 expression while restoring phosphorylated p38, MyoD, and myogenin expression, indicating suppression of atrophy- and remodeling-related responses, together with the recovery of myogenic signaling. Among the major identified compounds, all attenuated dexamethasone-induced myotube atrophy and quercetin showed the most pronounced morphological recovery. Molecular docking analysis targeting p38α showed the highest binding affinity for α-tocopherol, followed by quercetin and ascorbic acid, supporting potential interactions between the major compounds and p38 MAPK-related signaling. Conclusions: Collectively, these findings suggest that M. charantia attenuates sarcopenic changes by promoting myogenic differentiation and modulating the p38 MAPK-associated pathways.