Shentong Zhuyu Decoction mitigates exercise-induced muscle damage through modulation of AMPK-mediated lipid metabolism and oxidative stress.

Abstract

ETHNOPHARMACOLOGY-ASSOCIATED: Shentong Zhuyu Decoction (STZYD) is a traditional Chinese medicine formula based on the theory of "qi and blood obstruction", which has important ethnopharmacology significance in the treatment of exercise-induced muscle damage (EIMD). Our animal studies have shown that STZYD regulates lipid metabolism and oxidative stress through the AMPK signaling pathway, thereby linking traditional therapeutic knowledge ("promoting blood circulation and unblocking collaterals" therapy) with modern mechanistic insights. These findings highlight the unique value of ethnic medicine in treating systemic muscle pain. OBJECTIVE: EIMD is an inflammatory condition that frequently occurs after strenuous exercise and can have a certain impact on the physical and mental health of patients. However, the current mainstream treatment methods are relatively limited, posing significant therapeutic challenges. STZYD is a traditional Chinese medicinal formula widely used to address pain issues in humans, but its efficacy and mechanism in treating EIMD are not yet explicit. METHODS: Firstly, a mouse EIMD model was constructed, and the intervention effect of STZYD on EIMD was evaluated using methods such as histopathology, ELISA, and TUNEL staining. Subsequently, the chemical composition of STZYD was analyzed using UHPLC-MS/MS system. In addition, we jointly applied network pharmacology and RNA seq techniques to explore the potential mechanism of STZYD in treating EIMD. Finally, in vitro and in vivo experiments were conducted to validate the above conclusions and elucidate the specific mechanism by which STZYD affects EIMD. RESULTS: Our research indicates that STZYD treatment can significantly inhibit inflammation and apoptosis of skeletal muscle tissue, reduce IL-6, and increase the transcription and translation levels of Desmin and MyoD. Mass spectrometry analysis revealed 2202 phytochemicals, including 48 bioactive substances. The combined study of network pharmacology and RNA sequencing reveals that STZYD's treatment mechanism for EIMD may involve the activation of the AMPK signaling pathway, lipid metabolism process, and oxidative stress response. We validated these conclusions through in vitro and in vivo experiments, emphasizing the role of lipid metabolism and oxidative stress in skeletal muscle damage. CONCLUSION: This study reveals that STZYD alleviates skeletal muscle damage by activating the AMPK signaling pathway, regulating lipid metabolism, and oxidative stress responses in skeletal muscle, providing a potential therapeutic strategy for EIMD.