基于网络药理学和分子对接探析当归-川芎药对治疗股骨头坏死的作用机制

Study on the action mechanism of Danggui-Chuanxiong medicine pair in the treatment of femoral head necrosis based on network pharmacology and molecular docking

目的:运用网络药理学及分子对接技术研究当归-川芎药对治疗股骨头坏死的多靶点作用机制。方法:采用中药系统药理学数据库与分析平台(TCMSP)检索当归-川芎的有效成分及其作用靶点;采用GeneCards、OMIM、DrugBank等数据库检索股骨头坏死的疾病靶点;采用Cytoscape 3.9.1建立化合物-靶点-通路-疾病网络;使用STRING构建蛋白质-蛋白质相互作用网络;应用Metascape库进行基因本体论(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析;运用IGEMDOCK软件进行分子对接并进行对接效果的打分。结果:当归-川芎药对具有9个有效成分,有效成分的基因靶点与股骨头坏死基因靶点的交集基因有30个。通过对药物-有效成分-靶点-股骨头坏死调控网络的可视化分析,发现有效成分中的β-谷甾醇及杨梅酮所对应的交集基因最多。运用蛋白质-蛋白质相互作用网络预测到半胱氨酸蛋白酶3(Caspase 3,CASP3)、转录因子激活蛋白-1亚基(Transcription factor activator protein-1 subunit,JUN)、前列腺素G/H合酶2(Prostaglandin G/H Synthase 2,PTGS2)等30个基因是当归-川芎治疗股骨头坏死所干预的重要靶点。富集分析结果分析显示,当归-川芎有效成分在脂代谢相关生物过程、核受体相关分子作用、膜转运相关细胞组分中均可干预股骨头坏死。分子对接结果显示,当归-川芎药对中的叶酸、川芎萘呋内酯、川芎醌均与主要靶点结合良好,且较股骨头坏死有效药物结合趋势更强。结论:当归-川芎治疗股骨头坏死主要是作用于CASP3、JUN、PTGS2等30个基因,并在分子层面起到改善股骨头坏死脂代谢及微循环障碍等作用。

Objective:To study the multi-target action mechanism of Danggui(Radix Angelicae sinensis)-Chuanxiong(Rhizoma Chuanxiong)medicine pair in the treatment of femoral head necrosis by network pharmacology and molecular docking technology.Methods:The effective components and action targets of Danggui-Chuanxiong medicine pair were retrieved by TCMSP.The disease targets of femoral head necrosis were searched by GeneCards,OMIM,Drugbank and other databases.The compound-target-pathway-disease network was established by Cytoscape 3.9.1 software.The protein-protein interaction network was constructed by STRING database.Metascape database was used to perform the GO functional enrichment analysis and KEGG pathway enrichment analysis for target genes.IGEMDOCK software was used for molecular docking,and the docking effect was scored.Results:Danggui-Chuanxiong medicine pair had 9 effective components,and there were 30 intersection genes of the gene targets of effective component and the target of femoral head necrosis.Through the visual analysis of the regulatory network of medicine-active ingredient-target-femoral head necrosis,it was found that the intersection genes corresponding to active ingredients beta-sitosterol and myricanone were the most.The protein-protein interaction Vol.(15)No.25 network predicted that 30 genes such as CASP3,JUN and PTGS2 were important targets of Danggui-Chuanxiong medicine pair on femoral head necrosis.The results of GO function and KEGG pathway enrichment analysis showed that the active components of Danggui-Chuanxiong medicine pair could interfere with femoral head necrosis through biological processes related to lipid metabolism,nuclear receptor related molecules effects,and membrane transport related cell components.The results of molecular docking showed that folic acid,ligusticum naphthalene furolide,and ligusticum chuanxiong quinone in Danggui-Chuanxiong medicine pair all combined well with the main targets,and the binding trend was stronger than effective medicines for femoral head necrosis.Conclusion:The action mechanism of Danggui-Chuanxiong medicine pair in the treatment of femoral head necrosis is mainly to act on 30 genes such as CASP3,JUN,and PTGS2,and ameliorate lipid metabolism and microcirculation disorders after femoral head necrosis at the molecular level.