Anti-osteoporotic Effect of Solanum xanthocarpum Leaf Extract on Retinoic Acid-induced Osteoporosis in Rats via Alleviating Osteoclastic Activity

Background: (SX), a wild herb in the Solanaceae family, has traditionally been used to manage postmenopausal symptoms and articular cartilage injury. Objectives: leaf extract (SXLE) in a rat model of retinoic acid (RA)-induced osteoporosis. Methods: Female Sprague-Dawley (SD) rats were randomly assigned to six experimental groups (n = 6 per group): group I, control; group II, RA alone (75 mg/kg body weight/day); group III, RA + alendronate (5 mg/kg body weight); group IV, RA + SXLE (25 mg/kg body weight); group V, RA + SXLE (50 mg/kg body weight); and group VI, RA + SXLE (100 mg/kg body weight). Bone mineral density (BMD), bone length, bone mineral content, serum estradiol levels, osteocalcin (OCN), alkaline phosphatase (ALP), and tartrate-resistant acid phosphatase (TRAP) activity were measured. The mRNA expression levels of TNF-α, IL-6, TP53 (tumor protein p53), NOX1 (NADPH oxidase 1), NOX2 (NADPH oxidase 2), SOD1 (superoxide dismutase 1), and SOD2 (superoxide dismutase 2) were evaluated by RT-qPCR. Results: SXLE treatment significantly increased body weight, bone mineral content, bone length, relative bone density, serum estradiol, osteocalcin, and BMD in a dose-dependent manner. Conversely, SXLE dose-dependently reduced ALP and TRAP activities and decreased the mRNA expression of TNF-α, IL-6, and TP53. SXLE improved tibial and femoral coefficients and lengths, increased trabecular relative bone density, and enhanced the cortical bone area ratio. The therapeutic effects of SXLE at 100 mg/kg body weight were comparable to those of alendronate (5 mg/kg body weight). Furthermore, SXLE downregulated the expression of NOX1 and NOX2 while upregulating the expression of SOD1 and SOD2. Conclusions: SXLE enhances osteoblastic/osteogenic activity while suppressing osteoclastic activity, indicating significant anti-osteoporotic potential in rats with RA-induced osteoporosis. This is the first report to link SXLE to modulation of the NOX1/NOX2-SOD1/SOD2 oxidative stress pathway in bone, providing a potential molecular mechanism for its bone-protective effects. In addition, SXLE at 100 mg/kg demonstrated therapeutic efficacy comparable to that of alendronate, supporting its potential as a plant-based alternative to bisphosphonates for osteoporosis management.