基于网络药理学和分子对接的灯盏细辛对高血压的作用机制研究

Research on Mechanism of Action of Erigeron Breviscapus on Hypertension Based on Network Pharmacology and Molecular Docking

目的:应用网络药理学和分子对接技术,探究灯盏细辛治疗高血压的作用机制。方法:借助中药系统药理学平台检索灯盏细辛的活性成分及其作用靶点,在GeneCards、TTD和OMIM数据库检索高血压的相关蛋白靶点,通过Uniprot数据库和STRING数据库获取靶点的基因名称;绘制韦恩图(Venn-diagram),得到交集靶点,随后利用Cytoscape 3.10.0版软件构建“灯盏细辛-成分-高血压-靶点”网络图获取主要的化合物成分,然后通过构建蛋白质-蛋白质相互作用(protein-protein interactions,PPI)网络获取灯盏细辛治疗高血压的主要靶点;再利用DAVID数据库对药物和疾病的交集靶点进行GO功能富集分析和KEGG通路富集分析;最后,对主要化合物和主要靶点进行分子对接验证,计算结合能。结果:经筛选,得到灯盏细辛作用靶点207个、高血压相关靶点1585个和交集靶点113个;其中,Degree值前5位的成分依次为槲皮素、山柰酚、木犀草素、刺芒柄花素、黄芩素,而Degree值前5位的交集靶点依次为蛋白转录因子激活蛋白1(JUN)、抑癌基因p53(TP53)、热休克蛋白HSP90-α(HSP90AA1)、丝氨酸/苏氨酸激酶1(AKT1)、丝裂原活化蛋白激酶1(MAPK1);GO功能富集分析和KEGG通路富集分析结果显示,活性氧信号通路、PI3K-Akt、肿瘤坏死因子信号通路等是灯盏细辛治疗高血压的主要通路;分子对接结果显示,前5位成分和前5位交集靶点的结合能均小于-5 kJ/mol,表明主要成分和主要靶点的结合较好。结论:灯盏细辛中的主要活性成分可以较好地与高血压的治疗靶点相结合,因而具有可开发成为治疗高血压药物的潜在可能。

Objective:To explore the mechanism of action of erigeron breviscapus in treating hypertension using network pharmacology and molecular docking techniques.Methods:The active ingredients of erigeron breviscapus and its targets were searched on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,and the related protein targets of hypertension were searched in GeneCards,TTD and OMIM databases,and the gene names of the targets were available in the Uniprot and STRING databases.A Venn diagram was drawn to obtain the intersection targets.Then,the"erigeron breviscapus-ingredients-hypertension-targets"network diagram was constructed using the software Cytoscape 3.10.0 to obtain the main compound components,and then the main targets of erigeron breviscapus for the treatment of hypertension were obtained by constructing a protein-protein interactions(PPI)network;the DAVID database was used to perform GO functional enrichment analysis and KEGG pathway enrichment analysis on the intersection targets of drugs and diseases.Finally,molecular docking verification was performed on the main compounds and main targets,and the binding energy was calculated.Results:After screening,207 targets of erigeron breviscapus,1585 hypertension-related targets and 113 intersection targets were obtained;among them,the top 5 components with the highest degree value were quercetin,kaempferol,luteolin,formononetin and baicalein,and the top 5 intersection targets with the highest degree value were transcription factor activator protein 1(JUN),tumor suppressor gene p53(TP53),heat shock protein HSP90-α(HSP90AA1),serine/threonine kinase 1(AKT1),mitogen-activated protein kinase 1(MAPK1).The GO functional enrichment analysis and KEGG pathway enrichment analysis showed that the reactive oxygen species signaling pathway,PI3K-Akt,tumor necrosis factor(TNF)signaling pathway,etc.were the main pathways of erigeron breviscapus in treating hypertension.The molecular docking results showed that the binding energy of the top 5 components and the top 5 intersection targets was less than-5 kJ/mol,indicating that the main components bound with the main targets well.Conclusion:The main active ingredients in erigeron breviscapus can bind with the therapeutic targets of hypertension well,so it is potentially developed into a drug for the treatment of hypertension.