Anti-osteoporotic impact of Lepidium sativum seed extract and green-synthesized silver nanoparticles in a rat model of osteoporosis: possible TNF-α/RANKL modulation

Osteoporosis is a major health concern, and dexamethasone-induced secondary osteoporosis disrupts bone remodeling and mineral homeostasis, increasing fracture risk. Natural plant extracts and their nanoparticle formulations have emerged as promising therapeutic approaches. This study evaluated the anti-osteoporotic effects of ethanolic Lepidium sativum seed extract (LSE) and its green-synthesized silver nanoparticles (LSE-Ag) in a rat model of dexamethasone-induced osteoporosis. Male rats received dexamethasone (0.1 mg/kg/day, subcutaneously) for 8 weeks and were assigned to six groups: Control, Osteoporotic (OP), LSE, LSE-Ag, OP + LSE, and OP + LSE-Ag. LSE was analyzed by HPLC, and LSE-Ag was characterized by UV–Vis, FTIR, TEM, DLS, and XRD. Body weight, bone mineral density, serum minerals, vitamin D, alkaline phosphatase, osteocalcin, TNF-α, RANKL expression, antioxidant status, and bone histopathology were evaluated. Dexamethasone caused body weight loss, reduced bone mineral density, impaired bone turnover and mineral homeostasis, increased oxidative stress, elevated TNF-α and RANKL, and deterioration of bone microarchitecture. LSE and LSE-Ag improved several osteoporosis-related parameters. Lepidium sativum seed extract and its green-synthesized silver nanoparticles demonstrated promising anti-osteoporotic activity, possibly through modulation of oxidative stress, TNF-α, and RANKL signaling. Further studies are needed to confirm their therapeutic potential in glucocorticoid-induced osteoporosis.