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| 剑叶龙血素对破骨细胞分化影响的研究 |
| Study on the effect of Cochinchinenin A on osteoclast differentiation |
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| DOI：10.3969/j.issn.1006-7108.2024.10.001 |
| 中文关键词: 剑叶龙血素A 破骨细胞 网络药理学 分子对接 作用机制 MAPK |
| 英文关键词:Cochinchinenin A osteoclast network pharmacology molecular docking mechanism of action MAPK |
| 基金项目:国家自然科学基金（82104883）；广州中医药大学第一附属医院中青年骨干人才培育项目（中医医院[2023]186号）；广州市科技计划项目优秀博士续航项目（2024A04J9998） |
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| 中文摘要: |
| 目的 探讨剑叶龙血素A（Cochinchinenin A，CCA）对破骨细胞分化的影响及作用机制。方法 采用网络药理学技术预测CCA干预破骨细胞分化的作用机制，并用Auto Dock Tool 软件对CCA与破骨细胞分化关键靶点进行分子对接。体外采用巨噬细胞集落刺激因子（macrophage colony-stimulating factor，M-CSF）和核因子受体配体激活因子（receptor activator of nuclear factor kappa-B ligand，RANKL）诱导小鼠骨髓巨噬细胞（bone marrow macrophages，BMMs）分化为破骨细胞，并通过抗酒石酸酸性磷酸酶（TRAcP）和F-actin染色观察CCA对破骨细胞形成的影响，最后通过Western Blot检测CCA对MAPK和NF-κB信号通路的调控作用。结果 通过网络药理学技术共筛选获得20个CCA抗破骨细胞分化的潜在靶点，功能富集分析发现CCA可通过调节MAPK、破骨细胞分化和肌动蛋白细胞骨架组成等信号通路及PIK3CA、MTOR、ESR1及MAPK1等关键靶点发挥抑制破骨细胞分化的作用。分子对接进一步验证了CCA和关键靶点的结合能力。体外实验结果表明CCA可显著抑制RANKL诱导的破骨细胞分化及F-actin形成，同时抑制NFATc1、Integrin β3、c-Fos蛋白及破骨细胞功能相关蛋白CTSK的表达。此外，CCA抑制了p38的磷酸化和IκB-α的降解。结论 CCA可通过调控p38/MAPK及NF-κB信号通路从而抑制破骨细胞分化。 |
| 英文摘要: |
| Objective The purpose of this study was to investigate the effects and mechanisms of Cochinchinenin A (CCA) on osteoclast differentiation. Methods Network pharmacology techniques were used to analyze the mechanisms of CCA intervention in osteoclast differentiation. Molecular docking was performed using Auto Dock Tool software to examine the binding of CCA to key targets involved in osteoclast differentiation. In vitro，we utilized mouse bone marrow macrophages (BMMs) induced by macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-B ligand (RANKL) to explore the impact of CCA on osteoclastogenesis. The effects of CCA were monitored through tartrate-resistant acid phosphatase (TRAcP) and F-actin staining，which are indicative of osteoclast formation. Additionally，the regulatory role of CCA on the MAPK and NF-κB signaling pathways was assessed via Western blot analysis. Results Using network pharmacology techniques，20 potential targets for CCA in the suppression of osteoclast differentiation were identified. Enrichment analysis revealed that CCA can inhibit osteoclast differentiation through the regulation of MAPK signaling，osteoclast differentiation，and actin cytoskeleton composition pathways，as well as key targets such as PIK3CA，MTOR，ESR1，and MAPK1. Molecular docking further confirmed the binding abilities of CCA to these targets. In vitro experiments showed that CCA significantly inhibited RANKL-induced osteoclast differentiation and actin ring formation，while suppressing the expression of NFATc1，Integrin β3 and c-Fos proteins and osteoclast activity-related CTSK protein. Furthermore，CCA inhibited the phosphorylation of p38 and the degradation of IκB-α. ConclusionCCA can inhibit osteoclast differentiation by regulating the p38/MAPK and NF-κB signaling pathways. |
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