| Objective To investigate the effects of Silibinin on the bone mass of rat models with glucocorticoid-induced osteoporosis (GIOP). Methods Thirty male Sprague Dawley rats aged 12 weeks were randomly divided into three groups: the control group (n = 10) was intramuscularly injected with an equal volume of 0.9% sodium chloride；the dexamethasone group (n = 10) was intramuscularly injected with dexamethasone at 1 mg/kg (twice a week) to induce GIOP; the dexamethasone plus Garlic extract group (n = 10) was subcutaneously gavaged with Silibinin, simultaneously. The bilateral femurs were collected after 12 weeks to perform micro-computed tomography and bone biomechanical examinations. Also, tartrate-resistant acid phosphatase (TRACP), cross-linked carboxy-terminal telopeptide of type I collagen (CTX-I), alkaline phosphatase (ALP), and osteocalcin (OC) were tested. Western blot analysis of the effect of allicin on PI3K/AKT/FoxO1 pathway. Results The bone mineral density (BMD), bone microstructure, and bone biomechanical markers reduced significantly in the dexamethasone group compared with the control group(P<0.05). The bone resorption indicators (TRACP and CTX-I) increased, while the bone formation indicators (ALP and OC) decreased. After Silibinin treatment, BMD, bone microstructure, and bone biomechanical markers improved significantly. Moreover, TRACP and CTX-I decreased significantly, while ALP and OC increased compared with the dexamethasone group. Further studies have shown that Silibinin can regulate bone metabolism by inhibiting dexamethasone-mediated up-regulation of PI3K/AKT/FoxO1 signaling pathway. Conclusion Silibinin can regulate bone metabolism through PI3K/AKT/FoxO1 signaling pathway, and improve bone mineral density, bone microstructure and bone strength in GIOP rats. |