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Corylifol A suppresses osteoclastogenesis and alleviates ovariectomy-induced bone loss via attenuating ROS production and impairing mitochondrial function.
- Source :
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Biomedicine & Pharmacotherapy . Feb2024, Vol. 171, pN.PAG-N.PAG. 1p. - Publication Year :
- 2024
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Abstract
- 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. [Display omitted] • CorylifolA (Co-A) is a flavonoid compound extracted from psoralen, which has antibacterial and anti-inflammatory effects. • In vitro results showed that Co-A inhibited osteoclastogenesis through NFATc1, PI3K-AKT-GSK3β, ERK and Nrf2-Keap1 signaling pathways. • Co-A inhibits RANKL-induced osteoclastogenesis in vitro mainly through oxidative phosphorylation. • In vivo results showed that Co-A reduces bone loss in OVX mice by inhibiting osteoclast activity and function. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 07533322
- Volume :
- 171
- Database :
- Academic Search Index
- Journal :
- Biomedicine & Pharmacotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 175241066
- Full Text :
- https://doi.org/10.1016/j.biopha.2024.116166