Bu-Yang decoction attenuates OVX-induced sarcopenia by upregulating CXCR4 to suppress GPX4-mediated ferroptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Buyang Decoction (BYD), a traditional Chinese medicine formula, has demonstrated potential in strengthening muscles and bones, but its role in sarcopenia (SP) remains unclear. Ferroptosis is an iron-dependent form of regulated cell death triggered by lipid peroxidation, which plays a key role in the development of SP.

PURPOSE: This study investigated whether BYD alleviates SP by modulating ferroptosis via the CXCR4-GPX4 signaling axis.

MATERIALS AND

METHODS

OVX was used to model SP in vivo, with BYD administered at different concentrations. Therapeutic effects were assessed using behavioral tests, histochemistry, qRT-PCR, TEM, MRI, and micro-CT. In vitro, Erastin was used as an intervention, and techniques including WB, qRT-PCR, Nile red staining, DAFH-DA staining, and immunofluorescence were employed. GEO database analysis identified CXCR4 as a key gene. CXCR4 inhibition was performed pharmacologically in vivo and genetically in vitro.

RESULTS

In vivo, BYD enhanced muscle strength, differentiation, and GPX4 expression while reducing oxidative stress. In vitro, BYD promoted MuSCs (Muscle Satellite Cells) proliferation and differentiation while lowering oxidative stress and lipid peroxidation. In both in vivo and in vitro studies, CXCR4 inhibition resulted in the loss of BYD's therapeutic effects.

CONCLUSION

BYD mitigates SP by inhibiting ferroptosis via CXCR4-mediated GPX4 upregulation, highlighting CXCR4 as a potential therapeutic target.