基于网络药理学及分子对接分析当归-川芎药对治疗银屑病的作用机制

Mechanism of Angelicae Sinensis Radix-Chuanxiong Rhizoma in the Treatment of Psoriasis Based on Network Pharmacology and Molecular Docking

目的:运用网络药理学方法和分子对接技术,预测当归-川芎药对治疗银屑病的潜在分子作用机制。方法:通过中药系统药理学数据库与分析平台筛选出当归和川芎的有效活性成分以及具体的功效靶点,通过检索GeneCards、人类孟德尔遗传综合数据库、DrugBank和DisGeNET数据库,获得银屑病相关靶点。利用Venn网页工具获取药物疾病共同靶点,将其输入Cytoscape 3.9.1软件绘制当归、川芎-共同靶点-银屑病网络图。运用STRING数据库及Cytoscape 3.9.1软件构建蛋白质-蛋白质相互作用网络,通过DAVID数据库进行基因本体(GO)、京都基因与基因组百科全书(KEGG)富集分析,用微生信绘制富集分析的气泡图。利用AutoDock软件对分子对接进行验证,并用PyMOL软件对分子对接进行可视化。结果:获取当归、川芎治疗银屑病的有效活性成分9个,潜在作用靶点28个,关键作用靶点为胱天蛋白酶3、环氧化酶2、雌激素受体1、转录因子AP-1和丝裂原激活的蛋白激酶14。主要涉及药物的反应信号通路、细胞内类固醇激素受体信号通路、磷脂酰肌醇3激酶-蛋白激酶B信号通路和白细胞介素17信号通路等。结论:当归-川芎药对通过多通路、多种有效活性成分和多种有效靶点实现对银屑病的治疗。

OBJECTIVE:To predict the potential molecular mechanism of Angelicae sinensis radix-Chuanxiong rhizoma in the treatment of psoriasis based on network pharmacology and molecular docking techniques.METHODS:Active components and specific functional targets of Angelicae sinensis radix-Chuanxiong rhizoma were screened out by using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,psoriasis-related targets were obtained by retrieving GeneCard,OMIM,DrugBank and DisGeNET databases.The drug-disease common targets were acquired by using Venn web tools,which were imported into Cytoscape 3.9.1 software to map Angelicae sinensis radix-Chuanxiong rhizoma-common targets-psoriasis network diagram.The protein-protein interaction network was constructed by STRING database and Cytoscape 3.9.1 software,the Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed by DAVID database,the bubble diagram of enrichment analysis was made through bioinformatics.Molecular docking was verified by AutoDock software,and PyMOL software was using to conduct visualization on molecular docking.RESULTS:A total of 9 active ingredients and 28 potential targets were obtained from Angelicae sinensis radix-Chuanxiong rhizoma for the treatment of psoriasis,the key targets were Cystatinase 3,cyclooxygenase 2,estrogen receptor 1,transcription factor AP-1 and mitogen-activated protein kinase 14.Which mainly involved the drug-responsive signaling pathway,intracellular steroid hormone receptor signaling pathway,phosphatidylinositol 3-kinase-protein kinase B signaling pathway and interleukin 17 signaling pathway.CONCLUSIONS:Angelicae sinensis radix-Chuanxiong rhizoma realizes the treatment of psoriasis through multiple pathways,multiple active components and multiple effective targets.