Ginkgolide B alleviates HFD-induced osteoporosis in OVX mice by inhibiting oxidative stress and modulating gut microbiota.

Abstract

Estrogen deficiency and a high-fat diet (HFD) are both significant risk factors for osteoporosis, with HFD further exacerbating bone loss under estrogen-deficient conditions. Ginkgolide B (GB), a natural small molecule derived from Ginkgo biloba leaves, possesses various pharmacological effects; however, its role in osteoporosis induced by estrogen deficiency and HFD remains unexplored. In this study, we evaluated the effects of GB in ovariectomized (OVX) mice subjected to HFD (HFOVX model) and found that GB treatment attenuated bone loss through multiple biological changes. GB improved bone microarchitecture, increased trabecular number, and reduced bone marrow adipose tissue accumulation. Additionally, GB alleviated oxidative stress by lowering serum malondialdehyde (MDA) levels and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels while also reducing circulating lipopolysaccharide (LPS) levels. Furthermore, GB partially modulated the gut microbiota composition in HFOVX mice, as indicated by an increased relative abundance of potentially beneficial taxa such as Lactobacillaceae (e.g., Lactobacillus) and a decreased abundance of certain families associated with gut dysbiosis, including Ruminococcaceae, Helicobacteraceae (e.g., Helicobacter), and Desulfovibrionaceae. These microbial shifts were accompanied by lower circulating LPS and oxidative stress markers, suggesting a possible link between gut microbiota alterations and systemic inflammatory status. While these findings do not establish direct causality, they support the hypothesis that GB may exert bone-protective effects, at least in part, by modulating the gut microenvironment and systemic oxidative stress. Taken together, this study provides preliminary evidence for the therapeutic potential of GB in obesity-related postmenopausal osteoporosis and lays the groundwork for future mechanistic investigations.