Effect of isobavachalcone targeting ALOX5 to regulate ferroptosis in improving dexamethasone-induced osteoporosis

Objective The present study was undertaken to explore the effect of isobavachalcone (IBC) targeting Arachidonate 5-Lipoxygenase (ALOX5) to regulate ferroptosis in improving dexamethasone-induced osteoporosis. Materials and methods A total of sixty C57BL/6 J mice were allocated into six groups: normal control group (NC group, normal saline), osteoporosis model group (OP group, dexamethasone), positive control group (PC group, dexamethasone + alendronate sodium), low-dose isobavachalcone group (LD-IBC group, 10 mg/kg/d isobavachalcone), middle-dose isobavachalcone group (MD-IBC group, 20 mg/kg/d isobavachalcone), high-dose isobavachalcone group (HD-IBC group, 50 mg/kg/d isobavachalcone). The serum specimens were collected for the quantification of biochemical markers of bone metabolism. Femoral tissues were collected to compute the femur index and to evaluate parameters. Biomechanical integrity was assessed by employing a three-point bending assay. H&E staining was used to observe bone tissue morphology, Tartrate-Resistant Acid Phosphatase (TRAP) staining was employed to assess osteoclast activity, and Western blotting was performed to detect the protein expression of ALOX5, Keap1, Nrf2, SLC7A11, and GPX4 in the left femur. Results When contrasted with the NC group, the OP group exhibited significantly reduced serum levels of alkaline phosphatase, osteocalcin, and osteoprotegerin, alongside marked elevations in C-terminal telopeptide of type I collagen, tartrate-resistant acid phosphatase 5 b, and soluble receptor activator of nuclear factor-κB ligand. Moreover, the OP group showed decreased femur index, BMD, BMC, maximum load, maximum stress, and bending elastic modulus, with increased TRAP-positive staining area. Femoral tissue analysis revealed downregulation of ALOX5, Nrf2, SLC7A11, and GPX4, while Keap1 was significantly upregulated ( P < 0.05). Conclusion Isobavachalcone can improve dexamethasone-induced osteoporosis by targeting ALOX5 and inhibiting ferroptosis-related pathways, providing a new experimental basis for its prevention and treatment.