Corylifol A suppresses osteoclastogenesis and alleviates ovariectomy-induced bone loss via attenuating ROS production and impairing mitochondrial function

作者：Li, Haishan; Deng, Wei; Yang, Jiamin; Lin, Yuewei; Zhang, Shiyin; Liang, Zixuan; Chen, Junchun; Hu, Minhua; Liu, Teng; Mo, Guoye; Zhang, Zhen; Wang, Dongping; Gu, Peng; Tang, Yongchao; Yuan, Kai; Xu, Liangliang; Xu, Jiake^*; Zhang, Shuncong^*; Li, Yongxian^*

来源：Biomedicine and Pharmacotherapy, 2024, 171: 116166.

DOI：10.1016/j.biopha.2024.116166

• Corylifol A
• Osteoclastogenesis
• PI3K-AKT
• Reactive oxygen species
• Oxidative phosphorylation

Osteoporosis is a systemic disease characterized by an imbalance in bone homeostasis, where osteoblasts fail to fully compensate for the bone resorption induced by osteoclasts. Corylifol A, a flavonoid extracted from Fructus psoraleae, has been identified as a potential treatment for this condition. Predictions from network pharmacology and molecular docking studies suggest that Corylifol A exhibits strong binding affinity with NFATc1, Nrf2, PI3K, and AKT1. Empirical evidence from in vivo experiments indicates that Corylifol A significantly mitigates systemic bone loss induced by ovariectomy by suppressing both the generation and activation of osteoclasts. In vitro studies further showed that Corylifol A inhibited the activation of PI3K-AKT and MAPK pathways and calcium channels induced by RANKL in a time gradient manner, and specifically inhibited the phosphorylation of PI3K, AKT, GSK3 beta, ERK, CaMKII, CaMKIV, and Calmodulin. It also diminishes ROS production through Nrf2 activation, leading to a decrease in the expression of key regulators such as NFATcl, C-Fos, Acp5, Mmp9, and CTSK that are involved in osteoclastogenesis. Notably, our RNA-seq analysis suggests that Corylifol A primarily impacts mitochondrial energy metabolism by suppressing oxidative phosphorylation. Collectively, these findings

• 单位
  中国科学院; 广州中医药大学; 1; jk