基于网络药理学及分子对接探讨补肾和脉方核心中药治疗单纯性收缩期高血压作用机制

Mechanism of Core Medicinals in Bushen Hemai Formula(补肾和脉方) for IsolatedSystolic Hypertension Based on Network Pharmacology and Molecular Docking

目的:利用网络药理学和分子对接技术,研究补肾和脉方核心中药在单纯性收缩期高血压(ISH)治疗中的潜在作用机制。方法:在中药系统药理学数据库(TCMSP)中检索补肾和脉方核心中药的化学成分以及作用靶点,通过多个数据库检索与ISH治疗相关的靶点,利用R4.0.2软件中的Venn包对药物靶点与疾病靶点取交集。利用STRING数据库构建靶点蛋白-蛋白相互作用(PPI)网络,使用Cytoscape的CytoNCA插件进行集中性分析,筛选出关键基因。利用R4.0.2软件以及拓展包对靶基因进行基因本体(GO)富集分析和京都基因和基因组数据库(KEGG)富集分析。利用AutoDockVina软件进行核心药物成分与靶点的分子对接。结果:在补肾和脉方核心药物中筛选出39种活性成分,并与疾病具有141个共同靶点。PPI拓扑分析筛选出转录因子JUN、丝裂原蛋白活化激酶1(MAPK1)、丝裂原蛋白活化激酶14(MAPK14)、肿瘤坏死因子(TNF)等13个核心靶点。GO生物过程分析显示,补肾和脉方治疗ISH可以影响脂多糖反应、循环系统中的血管进程和管径调节等多种生物过程。KEGG通路富集分析显示,主要涉及流体剪切应力与动脉粥样硬化、糖尿病并发症中的AGE-RAGE信号通路以及肿瘤坏死因子信号通路等。分子对接显示核心药物中的山柰酚和槲皮素等化学成分分别与JUN和TNF等靶点蛋白对接良好。结论:初步明确了补肾和脉方核心中药治疗ISH的主要靶点和通路。

Objective:To study the mechanism of core medicinals in Bushen Hemai Formula(补肾和脉方)for isolated systolic hypertension(ISH)based on network pharmacology and molecular docking. Methods:The chemical components and targets of core herbal of Bushen Hemai Formula were retrieved in the traditional Chinese medicine System Pharmacology(TCMSP) Database,and the targets related to treatment of ISH were retrieved through multiple databases. The intersection of drug targets and disease targets was obtained by using the Venn package in R4.0.2 software. Target protein-protein interaction(PPI) network was constructed using STRING database,and CytoNCA plug-in from Cytoscape was used for concentration analysis to screen out key genes. R software 4.0.2 and expansion package were used for gene ontology(GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomics(KEGG) pathway enrichment analysis of target genes. AutoDock Vina software was used for the molecular docking of core drug components and targets. Results:Among the core medicinals of Bushen Hemai formula,39 active components were screened out sharing 141 common targets with diseases. 13 key targets,such as JUN,mitogen-activated protein kinase 1(MAPK 1),MAPK14 and tumor necrosis factor(TNF),were screened out by PPI topological analysis. GO biological process analysis showed that Bushen Hemai Formula could affect various biological processes such as response to lipopolysaccharide,vascular process in circulatory system,regulation of tube diameter and so on. KEGG pathway enrichment analysis showed that this formula was mainly involved in fluid shear stress and AGE-RAGE signaling pathway in atherosclerosis and diabetic complications,TNF signaling pathway. Molecular docking showed that kaempferol and quercetin in the core herbal were well docked with JUN and TNF,respectively. Conclusion:In this study,the main targets and pathways of core medicinals of Bushen Hemai Formula in treating ISH were preliminarily identified.