Fructus Ligustri Lucidi inhibits ferroptosis in ovariectomy­induced osteoporosis in rats via the Nrf2/HO­1 signaling pathway.

ABSTRACT

Postmenopausal osteoporosis (PMOP) has increased in prevalence in recent years, thus researchers have evaluated alternative medicine therapies. Fructus Ligustri Lucidi (FLL) can inhibit bone loss, and ferroptosis serves an important role in osteoporosis. Therefore, the present study assessed the presence of ferroptosis in PMOP and whether FLL could inhibit ferroptosis to improve bone microstructure in ovariectomized rats. Ovariectomized rats were treated with FLL (1.56 g/kg/day) for 12 weeks. Micro-CT was performed to evaluate the bone microstructure and bone mineral density. Western blotting and reverse transcription-quantitative PCR were performed to assess the relative expression levels of proteins and mRNA. Subsequently, malondialdehyde (MDA) and Fe2+ assay kits were used to quantify the MDA and Fe2+ content, respectively. The results demonstrated that ovariectomy (OVX) resulted in iron overload and the accumulation of lipid peroxide. Furthermore, the expression of key factors that inhibited ferroptosis, glutathione peroxidase 4 and solute carrier family 7 member 11 was significantly downregulated in ovariectomized rats, which was significantly reversed by FLL treatment. Furthermore, bone formation was assessed using the expression of osteogenesis-related genes, runt-related transcription factor 2 and osterix, which revealed significantly higher levels in FLL-treated rats compared with ovariectomized rats. The levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were also significantly recovered following FLL treatment. In the present study, OVX of postmenopausal osteoporotic rats was found to induce ferroptosis by enhancing lipid peroxidation and Fe2+ levels. FLL significantly suppressed ferroptosis, protected the osteogenic ability of ovariectomized rats and promoted the Nrf2/HO-1 signaling pathway.