Water Extract of Polygonati Rhizoma Ameliorates Obesity-Related Skeletal Muscle Atrophy in Mice and C2C12 Myotubes

<b>Background:</b> Sarcopenic obesity (SO) is a metabolic myopathy characterized by the coexistence of obesity and decline of muscle mass and function. Obesity-related muscle atrophy represents a central pathological feature of this condition. Polygonati Rhizoma is widely used as a dietary herb with tonic effects in traditional Asian medicine. This study aims to investigate the effects and underlying molecular mechanisms of the water extract of Polygonati Rhizoma (WPR) on obesity-related muscle atrophy. <b>Methods:</b> The effects and potential mechanisms of WPR were explored using an obesity-induced muscle atrophy (OIMA) mouse model, palmitic acid (PA)- or lipopolysaccharide (LPS)-induced myotube atrophy models, and a myogenic differentiation model in C2C12 cells. <b>Results:</b> In OIMA mice, WPR attenuated obesity-related skeletal muscle atrophy and improved muscle strength and endurance. In the gastrocnemius muscle, WPR-treated mice showed lower levels of oxidative stress and inflammation, increased markers of mitochondrial biogenesis, and an improved balance between protein synthesis and degradation. In PA- or LPS-induced myotube atrophy models, WPR treatment suppressed the ubiquitin-proteasome system (UPS)-mediated proteolysis and NFκB/MAPK-related inflammatory signaling. In addition, WPR promoted myogenic differentiation in C2C12 myoblasts, which was associated with regulation of the p38 MAPK/MyoD/Myogenin axis. <b>Conclusions:</b> Our study suggests that WPR exerts a potential mitigating effect on obesity-related muscle atrophy, and this effect may be associated with the modulation of skeletal muscle inflammatory signaling, mitochondrial function, and protein metabolic balance. These findings are exploratory and provide mechanistic clues for future research aimed at developing potential intervention strategies for obesity-related muscle atrophy.