Li Hao, Cao Fangming, Liu Dian, Tao Lin
Department of Orthopedics, First Hospital of China Medical University, Shenyang, Liaoning, PR China.
Commun Biol. 2025 Sep 26;8(1):1367. doi: 10.1038/s42003-025-08751-z.
Zingerone, a component of dried ginger, has known anti-ulcer and bone growth-promoting effects, but its impact on postmenopausal osteoporosis (PO) is unclear. This study investigates the therapeutic potential and underlying mechanisms of zingerone in PO. A concentration-dependent effect identified on osteoclast precursors: at low concentrations, zingerone maintains low ROS levels, enhance proliferation, and facilitates bone remodelling; at high concentrations, it elevates ROS levels, enhances ferroptosis sensitivity, and suppresses osteoclast formation. Zingerone significantly improves bone mass in an ovariectomised mouse model of PO. Metabolomics identifies 869 differential metabolites linked to glutathione and purine metabolism. Transcriptomics highlights pathways including ferroptosis, leukocyte migration, and cell adhesion. In RAW264.7 cells, zingerone modulates p53, enhances ferroptosis sensitivity, increasing ROS and Fe, upregulates Sat1, and downregulates Gpx4, suggesting that zingerone may act via p53-mediated ferroptosis, indicating potential clinical utility. Before clinical application, the dose-dependent effects of zingerone on bone remodelling and its underlying mechanisms warrant further investigation.
姜辣素是干姜的一种成分，已知具有抗溃疡和促进骨骼生长的作用，但其对绝经后骨质疏松症（PO）的影响尚不清楚。本研究调查了姜辣素在PO中的治疗潜力及其潜在机制。在破骨细胞前体上发现了浓度依赖性效应：在低浓度下，姜辣素维持低ROS水平，增强增殖，并促进骨重塑；在高浓度下，它提高ROS水平，增强铁死亡敏感性，并抑制破骨细胞形成。姜辣素在去卵巢的PO小鼠模型中显著改善骨量。代谢组学鉴定出869种与谷胱甘肽和嘌呤代谢相关的差异代谢物。转录组学突出了包括铁死亡、白细胞迁移和细胞粘附在内的途径。在RAW264.7细胞中，姜辣素调节p53，增强铁死亡敏感性，增加ROS和铁，上调Sat1，并下调Gpx4，表明姜辣素可能通过p53介导的铁死亡发挥作用，显示出潜在的临床应用价值。在临床应用之前，姜辣素对骨重塑的剂量依赖性效应及其潜在机制值得进一步研究。
