Ginsenoside Rc inhibits TGF-β signaling and downregulates nucleolin to mitigate oxidative stress-induced muscle atrophy.

Ginsenoside Rc (gRc), a component of Panax ginseng, protects against muscle atrophy in in vitro and in vivo models; however, the underlying molecular mechanisms remain unclear. Through systematic transcriptomic analysis and docking simulation, we investigated these protective effects on muscle cells under oxidative stress. Pathway analysis revealed that gRc significantly suppressed oxidative stress-induced transforming growth factor-beta (TGF-β) signaling. Molecular docking indicated that gRc bound to TGF-β receptor 1 (TGFBR1), similar to known TGFBR1 inhibitors. Gene expression analysis identified nucleolin (Ncl), a downstream effector of TGF-β signaling, as a key target of gRc. Ncl silencing confirmed that gRc protected myotubes from degradation via the TGF-β-Ncl axis. Cross-sectional analysis of human muscle transcriptomic data demonstrated the relevance of targeting Ncl under muscle atrophy-related conditions. Overall, gRc alleviates oxidative stress-induced muscle atrophy by inhibiting TGF-β signaling and downregulating Ncl expression, highlighting its therapeutic potential.