Shenling Baizhu Decoction Improves Chemotherapy-Induced Sarcopenia by Regulating the NLRP3 Inflammasome and Muscle Metabolism

OBJECTIVE: This study investigated the effects of Shenling Baizhu decoction (SLBZD) on chemotherapy-induced sarcopenia and its potential mechanisms. METHODS: A mouse model of chemotherapy-induced sarcopenia was established and treated with SLBZD. The effects of SLBZD on body weight, food intake, muscle mass, muscle functional markers, muscle tissue architecture, and serum biochemical parameters in mice receiving chemotherapy were determined, and the potential mechanism was investigated. RESULTS: The study indicated that SLBZD effectively alleviated chemotherapy-induced weight loss and decreased food intake, muscle atrophy, and functional loss in mice. It increased the CSA level, decreased the serum IFN-γ, IL-1β, and TNF-α levels, increased ATP content and IGF-1 protein expression in muscle tissue, and down-regulated MSTN expression. SLBZD down-regulated the mRNA expressions of NLRP3, p65, Caspase-1, and MuRF1 and up-regulated the expression of MyoD. The mechanism is that SLBZD activated PPARγ, inhibited NF-κB phosphorylation, and suppressed NLRP3 inflammasome activation. Transcriptome analysis revealed the regulation of immune-inflammatory pathways and metabolic pathways. Additionally, SLBZD promoted myotube formation and diameter, regulated MuRF1/MyoD, and inhibited NLRP3/NF-κB signaling, effects that could be reversed by a PPARγ inhibitor. DISCUSSION: The findings suggest that SLBZD can prevent sarcopenia by activating PPARγ to inhibit NF-κB/NLRP3 and restore metabolic homeostasis, thereby making it a promising adjunctive therapeutic regimen. CONCLUSION: This study identifies SLBZD as a promising therapeutic agent for chemotherapy- induced sarcopenia, whose functions may be attributed to PPARγ-mediated regulation of inflammatory and metabolic pathways.