<br>Corylifol A 通过减少 ROS 产生和损害线粒体功能来抑制破骨细胞生成并减轻卵巢切除术引起的骨质流失,Biomedicine & Pharmacotherapy

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Corylifol A 通过减少 ROS 产生和损害线粒体功能来抑制破骨细胞生成并减轻卵巢切除术引起的骨质流失
Biomedicine & Pharmacotherapy ( IF 6.9 ) Pub Date : 2024-01-19 , DOI: 10.1016/j.biopha.2024.116166
HaiShan Li ₁ , Wei Deng ₁ , JiaMin Yang ₁ , YueWei Lin ₁ , ShiYin Zhang ₂ , ZiXuan Liang ₂ , JunChun Chen ₃ , MinHua Hu ₁ , Teng Liu ₁ , GuoYe Mo ₄ , Zhen Zhang ₁ , DongPing Wang ₁ , Peng Gu ₁ , YongChao Tang ₄ , Kai Yuan ₄ , LiangLiang Xu ₄ , JiaKe Xu ₃ , ShunCong Zhang ₄ , YongXian Li ₄

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骨质疏松症是一种全身性疾病，其特征是骨稳态失衡，成骨细胞无法完全补偿破骨细胞引起的骨吸收。 Corylifol A 是一种从补骨脂中提取的黄酮类化合物，已被确定为治疗这种疾病的潜在方法。网络药理学和分子对接研究的预测表明 Corylifol A 与 NFATc1、Nrf2、PI3K 和 AKT1 表现出很强的结合亲和力。体内实验的经验证据表明 Corylifol A 通过抑制破骨细胞的生成和活化，显着减轻卵巢切除术引起的全身性骨质流失。体外研究进一步表明，Corylifol A 以时间梯度方式抑制 RANKL 诱导的 PI3K-AKT 和 MAPK 通路及钙通道的激活，并特异性抑制 PI3K、AKT、GSK3 β、ERK、CaMKII、CaMKIV 和钙调蛋白。它还通过 Nrf2 激活减少 ROS 的产生，导致参与破骨细胞生成的关键调节因子（如 NFATcl、C-Fos、Acp5、Mmp9 和 CTSK）的表达减少。值得注意的是，我们的 RNA-seq 分析表明 Corylifol A 主要通过抑制氧化磷酸化来影响线粒体能量代谢。总的来说，这些发现表明 Corylifol A 是一种新型破骨细胞生成抑制剂，为与过度骨吸收相关的疾病提供了潜在的治疗应用。

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

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.

更新日期：2024-01-19

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