Investigating the pharmacodynamic mechanism of Erxian decoction to alleviate sarcopenia generated by ovarian aging through the ER-mediated estrogen signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Erxian decoction (EXD) is widely used in the treatment of various gynecological conditions, including menopausal syndrome, ovarian insufficiency, and premature ovarian failure (POF). As society ages, the prevalence of postmenopausal osteoporosis (PMOP) rises annually, accompanied by a progressive increase in the incidence of sarcopenia, a skeletal muscle disorder associated with osteoporosis. Recent studies have revealed that the diverse pharmacological agents and active compounds in EXD have been utilized in clinical and experimental contexts for sarcopenia; nevertheless, the mechanism by which EXD addresses postmenopausal sarcopenia remains unclear.

AIM OF THE STUDY: This study aims to elucidate the molecular mechanisms and active constituents of EXD in alleviating postmenopausal sarcopenia through a combination of network pharmacology and experimental validation both in vivo and in vitro.

MATERIALS AND METHODS: The potential anti-sarcopenic mechanisms of EXD were initially explored using network pharmacology. In vivo, successful construction of mouse model of ovarian aging. while forelimb grip strength and inverted hanging tests assessed muscle function. Levels of sex hormone secretion, muscle injury, and inflammatory markers were evaluated using ELISA, HE staining, Masson trichrome staining, and ATPase staining. IHC, RT-qPCR and Western blot analyses were conducted to quantify the expression of genes and proteins related to the estrogen signaling pathway and muscle atrophy. In vitro studies also utilized a C2C12 myotube atrophy model induced by Cisplatin. Cell proliferation was evaluated using the CCK-8 assay, apoptosis was assessed via flow cytometry, and expression levels of muscle-related proteins were determined through Western blot analysis.

RESULTS: Network pharmacology analysis suggested that the estrogen signaling pathway may play a key role in the mechanism by which EXD alleviates sarcopenia associated with ovarian aging. In vivo, EXD improved muscle strength in mice with ovarian aging, restored ovarian function, and prevented myofibrillar atrophy. In vitro, quercetin significantly reduced the apoptosis rate of C2C12 myotube cells and promoted cell proliferation, indicating its protective effect against muscle atrophy.

CONCLUSIONS: EXD can influence phytoestrogenic effects by regulating the estrogen signaling pathway to protect skeletal muscle in mice in ovarian aging.