Salidroside ameliorates glucocorticoid-induced osteoporosis by regulating the PI3K/Akt/mTOR pathway: a network pharmacology and in vivo

Osteoporosis (OP) is a bone disorder, common cause of bone fracture and disability. Management of it needs development of an alternative medicine and present report evaluates the protective effect of salidroside against glucocorticoid induced osteoporosis in rat model. Network pharmacology and docking study was performed to determine the molecular targets of salidroside against osteoporosis and its interaction with these targets. Twenty-four healthy male rats were separated into four different groups ( n = 6) such as control group; OP (Osteoporosis) group and salidroside 50 and 100 mg/kg groups. Osteoporosis was induced by the administration of dexamethasone (5 mg/kg, i.m.) twice in a week for the duration of 6 week and rats were treated with salidroside 50 and 100 mg/kg p.o. for the duration of 8 weeks. Bone mineral density (BMD) and parameters of osteoclast and osteoblast cell function were determined in the salidroside treated OP rats. Oxidative stress and inflammatory cytokines were estimated in OP rats. Data of the network pharmacology and docking study shows the effective binding of salidroside with Phosphoinositide 3-kinase (PI3K; -7.0 Kcal/mol) and Protein kinase B (Akt; -6.1 Kcal/mol) proteins to modulates the cellular function. Moreover, in vivo investigation shows significant increase ( p < 0.001) in the BMD of salidroside treated group than OP group of rats. Treatment with salidroside ameliorates the altered level of collagen type I fragments (CTX), tartrate-resistant acid phosphatase (TRAP), osteocalcin (OC) and activity of alkaline phosphatase (ALP) in OP rats. There was significant ( p < 0.001) reduction in oxidative stress and cytokines in the salidroside treated group than OP group of rats. mRNA expression of PI3K , Akt and mechanistic target of rapamycin ( mTOR ) and expression of PI3K, Akt and mTOR proteins were enhanced in the salidroside treated group than OP group of rats. In conclusion, data of the study reveals that treatment with salidroside ameliorates altered osteocyte function in glucocorticoid induced osteoporosis rats by regulating PI3K/Akt/mTOR pathway.