骨吸收
PI3K/AKT/mTOR通路
蛋白激酶B
化学
MAPK/ERK通路
兰克尔
骨重建
细胞生物学
磷酸化
骨质疏松症
内分泌学
下调和上调
内科学
癌症研究
信号转导
生物
医学
生物化学
激活剂(遗传学)
受体
基因
作者
HaiShan Li,Wei Deng,Jiamin Yang,Yuewei Lin,ShiYin Zhang,ZiXuan Liang,JunChun Chen,MinHua Hu,Teng Liu,Guo‐ye Mo,Zhen Zhang,DongPing Wang,Peng Gu,YongChao Tang,Kai Yuan,Liangliang Xu,Jiake Xu,Shuncong Zhang,YongXian Li
标识
DOI:10.1016/j.biopha.2024.116166
摘要
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 β, 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 demonstrate that Corylifol A is a novel inhibitor of osteoclastogenesis, offering potential therapeutic applications for diseases associated with excessive bone resorption.
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