Nuciferine ameliorates steroid-induced osteonecrosis of the femoral head by inhibiting BMSCs ferroptosis via HIF-1α.

作者：Wei-Qiang Sun, Jing Wang, Tanxin Yu, Shao-Han Xu, Dexin Lin, Qi Zhuang, Yufeng Tang, Changquan Liu, Xiao-Le Zhang, Huachen Yu · 发表于：Phytomedicine · 年份：2026 · DOI：10.1016/j.phymed.2026.158070 · 被引用次数：2 · 研究领域：Medicine

OBJECTIVE Glucocorticoid use is a leading cause of osteonecrosis of the femoral head, with the death of bone marrow mesenchymal stem cells (BMSCs) considered a central cellular event in steroid-induced osteonecrosis of the femoral head (SONFH). However, the underlying mechanisms remain unclear, and effective therapies are lacking. METHOD In this study, we established an in vitro model of SONFH by treating BMSCs with methylprednisolone (MP, 1 mM, 24 h) and screened a natural product library for inhibitors of the steroid-induced cell death (SiCD). RESULTS Our results demonstrated that 15 natural products may effectively inhibit SiCD among the screened library, with nuciferine emerging as one of the most potent compounds. Further study showed that nuciferine may predominantly suppress ferroptosis in glucocorticoid treated BMSCs, it may also promote osteogenic differentiation and mitochondrial homeostasis. Mechanistically, integrated bioinformatic analysis and gene knockdown experiments revealed that nuciferine relies on HIF-1α to inhibit ferroptosis and promote osteogenic differentiation. In vivo studies showed that administration of nuciferine effectively ameliorates SONFH in rats. CONCLUSIONS In summary, our study demonstrates that nuciferine may ameliorate SONFH by activating HIF-1α to suppress ferroptosis in BMSCs. Given that nuciferine is both a medicinal and dietary compound, it may also suggest that nuciferine could be a key dietary component for patients undergoing...