基于网络药理学和分子对接技术川牛膝治疗高血压机制研究

Study on the Mechanism of Achyranthes Radix in treating Hypertension

目的:基于网络药理学和分子对接技术探讨川牛膝治疗高血压的物质基础与分子机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)获取川牛膝的主要化学成分及其靶点,根据药物代谢动力学属性筛选小分子活性成分;基于多种基因数据库平台(GeneCards、OMIM和DurgBank)获取高血压疾病的主要靶点,并根据蛋白质相互作用分析数据库(STING)构建川牛膝-高血压病网络模型;采用基因功能数据库平台(Metascape)平台分析“药物-成分-靶点”及其参与的生物过程及通路,而后通过Cytoscape3.7.2软件构建“高血压活性成分-高血压疾病靶点-通路”网络,最后利用在线分子对接工具(CB-Dock Web Site)完成川牛膝降压活性成分与相关蛋白的分子对接验证。结果:川牛膝降压活性成分为β艾蒿素、红苋甾酮、β-谷甾醇和槲皮素,核心靶点为EGFR、ESR1、FOS和CCND1等,上述靶点分子对接验证评分均≥7,提示靶点与活性成分具有较强的结合活性能力。川牛膝治疗高血压的作用途径主要为流体剪切应力与动脉粥样硬化通路(Fluid shear stress and atherosclerosis)和糖尿病并发症晚期糖基化终末产物及其受体信号通路(AGE-RAGE signaling pathway in diabetic complications)等。结论:本研究初步揭示了川牛膝通过多成分、多靶点、多途径治疗高血压的作用机制,为川牛膝的临床应用和深度开发提供研究基础。

Objective:Based on network pharmacology and molecular docking technology,to explore the material basis and molecular mechanism of Achyranthes bidentata in treating hypertension.Methods:The main chemical components and targets of Achyranthes bidentata were obtained through the database and analysis platform of traditional Chinese medicine systemic pharmacology(TCMSP),and the small molecule active ingredients were screened according to the pharmacokinetic properties;based on a variety of gene database platforms(GeneCards,OMIM and DurgBank)to obtain the main targets of hypertension,and construct a network model of Achyranthes bidentata-hypertensive disease according to the protein interaction analysis database(STING);use the gene function database platform(Metascape)platform to analyze“drug-ingredient-target”and the biological processes and pathways involved,and then use the Cytoscape3.7.2 software to construct the“hypertensive active ingredient-hypertensive disease target-pathway”network,and finally use the online molecular docking tool(CB-Dock Web Site)to complete the CB-Dock Web Site.Molecular docking verification of active ingredients and related proteins.Results:The antihypertensive active ingredients of Chuan Achyranthes bidentata areβ-artemisinin,amaranthus sterone,β-sitosterol and quercetin,and the core targets are EGFR,ESR1,FOS and CCND1≥7,indicating that the target has a strong binding activity with the active ingredient.The pathways of Achyranthes bidentata in treating hypertension are mainly fluid shear stress and atherosclerosis pathway(Fluid shear stress and atherosclerosis)and diabetic complications advanced glycation end products and their receptor signaling pathway(AGE-RAGE signaling pathway).(pathway in diabetic complications),etc.Conclusion:This study preliminarily reveals the mechanism of action of Achyranthes bidentata in the treatment of hypertension through multi-components,multi-targets and multi-channels,and provides a research basis for the clinical application and indepth development of Achyranthes bidentata.