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Paeoniflorin, a natural product derived from  Paeonia lactiflora , possesses diverse pharmacological activities such as anti-inflammatory, antitumor, and antidiabetic effects. It has been reported for promoting osteoblastogenesis and inhibiting osteoclastogenesis. This study investigates the therapeutic effects of paeoniflorin in glucocorticoid-induced osteoporosis (GIOP)  in vitro  and  in vivo . MC3T3-E1 cells were incubated with dexamethasone (DEX; 200  μ M) and/or paeoniflorin (10  μ M), followed by the investigation of cell proliferation, differentiation, mineralization, apoptosis, and autophagy. The AKT activator SC79 was used for evaluating the involvement of the AKT/mTOR signaling pathway. After DEX pretreatments, paeoniflorin promoted osteoblast differentiation and mineralization characterized by increase in Runx2, ALP, beclin-1, and LC3-II/LC3-I ratio levels and a decrease in apoptosis. The autophagy-promoting effects of paeoniflorin were reversed by SC79. C57BL/6 mice were given DEX (1 mg/kg) once daily and paeoniflorin (15 mg/kg) 48 hours for a total of 8 weeks followed by the investigation of histological changes, the trabecular bone microarchitecture, and the levels of bone turnover markers. The results showed that paeoniflorin increased alkaline phosphatase (ALP) activity and upregulated the expression of osteocalcin and beclin-1 but reduced the levels of Bax and C-terminal telopeptide of type I collagen (CTX-1). Thus, paeoniflorin may alleviate DEX-induced osteoporosis by promoting osteogenic differentiation and autophagy via inhibition of the AKT/mTOR signaling pathway.

evidence-based complementary and alternative medicine

Paeoniflorin Attenuates Dexamethasone-Induced Apoptosis of Osteoblast Cells and Promotes Bone Formation via Regulating AKT/mTOR/Autophagy Signaling Pathway