Ginkgolide B modulates the gut-bone axis to ameliorate bone loss in ovariectomized mice.

SCOPE: Estrogen deficiency post-menopause is a key driver of bone loss and is often associated with disruption of the gut-bone axis. This study explored the therapeutic potential of Ginkgolide B (GB), a natural bioactive compound from Ginkgo biloba, in estrogen deficiency-induced bone loss using ovariectomized (OVX) mice.​. METHODS: Female SPF C57BL/6J mice were randomly divided into sham-operated (Sham), OVX, and OVX+GB groups. Osteoporosis was induced by bilateral ovariectomy, and GB was administered via oral gavage for 8 weeks. Evaluations included serum biochemical markers, bone microstructure (micro-CT, histomorphometry), intestinal barrier function (histology, immunohistochemistry, and Western blot), immune cell populations (flow cytometry), and gut microbiota composition (16S rRNA gene sequencing). RESULTS: GB treatment significantly mitigated bone loss in OVX mice, as confirmed by micro-CT, histological, and biochemical tests. GB enhanced intestinal barrier integrity by upregulating tight junction proteins and reducing pro-inflammatory markers. Flow cytometry showed that GB restored the balance of T helper 17 (Th17) and regulatory T (Treg) cells in the mesenteric lymph node and spleen, suggesting immune regulation. Additionally, GB modulated gut microbiota composition, increasing beneficial taxa like Lactobacillaceae and Prevotellaceae. Correlation analysis indicated significant associations between microbial taxa and serum markers and bone metabolism, highlighting the role of gut microbiota in GB's therapeutic effects on osteoporosis. CONCLUSION: GB is a promising natural bioactive compound for modulating bone health through the gut-bone axis, warranting further research to clarify underlying mechanisms.