Integrating Transcriptomics and Gut Microbiota Analysis Reveals the Anti‐Osteoporotic Mechanisms of Wine and Oil Co‐Processed Epimedium

Wine- and suet oil co-processed Epimedium (WSOEP) is a traditional Chinese herbal preparation produced by processing raw Epimedium with wine and suet oil as adjuvants. Although WSOEP has been used clinically for the treatment of osteoporosis, its precise therapeutic indications and underlying molecular mechanisms remain incompletely defined. This study integrates transcriptomic profiling with gut microbiota analysis to systematically elucidate the anti-osteoporotic efficacy of WSOEP and its mechanistic basis. In a mice model of osteoporosis induced by bilateral ovariectomy (OVX), WSOEP administration significantly attenuated bone loss and improved multiple key bone parameters compared to the Mod group. Mechanistically, WSOEP treatment markedly downregulated SRC protein expression while simultaneously upregulating both total STAT3 and p-STAT3, indicating restoration of the dysregulated SRC/STAT3 signaling axis. Furthermore, WSOEP effectively modulated gut microbial homeostasis by enriching beneficial taxa, including Bacilli, Verrucomicrobiae, and Bacteroidales, while suppressing potentially detrimental lineages such as Proteobacteria, Clostridia, and Akkermansia. This is the first study to demonstrate that WSOEP exerts robust protective effects against OVX-induced osteoporosis through dual modulation of the SRC/STAT3 pathway and the gut microbiome. These findings not only position WSOEP as a promising candidate for osteoporosis therapy but also offer a novel paradigm for multi-component herbal interventions targeting the gut-bone axis in metabolic bone diseases.