Hydroxysafflor yellow A attenuatesovariectomy induced bone loss andpromotes osteogenesis via PI3K/AKT activation in an in vitro BMSC model

Osteoporosis (OP) is a chronic systemic metabolic bone disorder that requires further exploration of effective treatments. An optimal anti-osteoporosis agent should exert dual effects on both osteoblasts and osteoclasts. Hydroxysafflor yellow A (HSYA), a flavonoid from the traditional Chinese medicinal plant safflower, is recognized as a potential candidate. This study shows that HSYA supports bone formation by stimulating osteoblast differentiation and increasing calcium nodule deposition. HSYA activates the PI3K/AKT signaling pathway and upregulates Runx2 expression in an in vitro osteoblast differentiation model using BMSCs. Concurrently, HSYA inhibit osteoclast differentiation, thereby mitigating the excessive bone resorption associated with osteoporosis. These findings indicate that HSYA mitigates bone loss in OP in vivo, while enhancing osteoblast activity and activating the PI3K/AKT pathway in an in vitro osteoblast differentiation model using BMSCs, and inhibiting osteoclast-driven bone resorption.