Isobavachin Modulates Bone Homeostasis Via Pi3k-Akt Signaling

Imbalance of bone-forming and -resorbing activities in the bone marrow microenvironment can cause osteoporosis. In recent years, traditional Chinese medicine ingredients have demonstrated promising potential in treating osteoporosis. This study investigates the effects of the natural flavonoid Isobavachin (IBA) on bone homeostasis and its potential osteoporosis treatment benefits. The impact of IBA on bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation was evaluated using qRT-PCR, WB, Alizarin Red staining, and alkaline phosphatase (ALP) staining. Investigating the mechanism of IBA on BMSCs osteogenic differentiation via network pharmacology analysis with molecular validation. The effects of IBA on osteoclast differentiation with BMMs were demonstrated in vitro through qRT-PCR and tartrate-resistant acid phosphatase (TRAP) staining. In vivo, the effects of IBA on OVX mice were assessed via histological staining, fluorescence labeling, and micro-computed tomography (micro-CT) scanning. All studies using famale C57/BL6 mice (6–8 weeks) were approved by Wuhan University Stomatology Ethics Committee. In vitro, IBA was found to enhance the osteogenic differentiation of BMSCs. Concurrently, through bioinformatics analysis, it was suggested that IBA's mechanism of action might involve the PI3K-AKT pathway. Additionally, IBA suppressed RANKL-induced osteoclastogenesis in BMMs. In vivo, IBA significantly improved bone mass and microarchitecture. The results indicated that IBA reversed bone loss in osteoporosis by promoting osteogenesis and inhibiting osteoclastogenesis. The data demonstrated that IBA exerts dual anti-osteoporotic effects through the PI3K-AKT pathway, suggesting it may be an ideal therapeutic agent for clinical medication of osteoporotic bone fracture.