Corylifol A suppresses osteoclastogenesis and alleviates ovariectomy-induced bone loss via attenuating ROS production and impairing mitochondrial function - 04/02/24
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.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | 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. |
Abbreviations : Co-A, BMMs, RANKL, RANK, NFATc1, C-Fos, TRAP, Mmp9, CTSK, ROS, OXPHOS, Acp5, Atp6vod2, ATP, NADPH, Nox1, NAC, DPI, Nrf2, Keap1, ARE, OVX, NF-κ B, MAPKs, RNA-seq, DMSO, PBS, P/S, FBS, Ho-1, SOD1, ERK, JNK, DAPI, M-CSF, PCR, DCFH-DA, TRAcP, TRAP, RIPA, SDS-PAGE, PVDF, ECL, BSA, F-actin, DCF, DCFH-DA, MMM, mtROS, Micro-CT, Tb.Sp, Tb.Th, Tb.N, Bv/Tv, EDTA, ANOVA, PFA
Keywords : Corylifol A, Osteoclastogenesis, PI3K-AKT, Reactive oxygen species, Oxidative phosphorylation
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Vol 171
Article 116166- février 2024 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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