基于网络药理学与分子对接技术探讨六味地黄丸治疗抑郁症的作用机制  

Investigate of Mechanism of Liuwei Dihuang Pill in Treatment of Depression Based on Network Pharmacology and Molecular Docking Technology

作　　者：张俊霞[1] 晁利芹[1] 王付[1] ZHANG Junxia;CHAO Liqin;WANG Fu(Henan University of Chinese Medicine,Zhengzhou Henan China 450046)

机构地区：[1]河南中医药大学,河南郑州450046

出　　处：《中医学报》2022年第8期1719-1726,共8页Acta Chinese Medicine

基　　金：国家自然科学基金项目(81804196);河南中医药大学博士基金项目(BSJJ2016-11)。

摘　　要：目的:采用网络药理学与分子对接技术研究六味地黄丸治疗抑郁症的作用机制。方法:采用中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)检索六味地黄丸组方中药的化学成分,利用TCMSP、PubChem数据库、BABEL软件、SwissTargetPrediction平台、SEA平台预测药物活性成分靶点;采用DisGeNET数据库获取抑郁症的靶点;运用Venn Diagram平台对六味地黄丸活性成分相关靶点及抑郁症疾病靶点进行映射,得到六味地黄丸治疗抑郁症的潜在作用靶点;将六味地黄丸治疗抑郁症的潜在作用靶点输入STRING数据库获取蛋白相互作用(protein-protein interaction,PPI)关系,并将结果输入Cytoscape 3.2.1软件构建PPI网络,筛选出关键靶点。将潜在作用靶点与六味地黄丸相关活性成分导入Cytoscape 3.2.1软件,构建“药物活性成分-潜在靶点”网络图,筛选出关键成分;将潜在靶点输入FunRich软件进行富集分析。应用DockThor软件将PPI网络中度值首位的靶点蛋白分别与六味中药中拓扑分析参数首位的活性成分进行分子对接,使用PyMOL软件做出可视化图片。结果:获得六味地黄丸活性成分40个,相关靶点3 706个;抑郁症疾病靶点1 478个,六味地黄丸治疗抑郁症潜在靶点38个。PPI网络拓扑分析筛选得到丝裂原活化蛋白激酶3(mitogen-activated protein kinase 3,MAPK3)为首位关键靶点。“药物活性成分-潜在靶点”网络拓扑分析筛选出关键成分为豆固醇、薯蓣皂苷、2,6,10,14,18-五甲基肼-2,6,10,14,18-五烯、丁子香萜等。将38个交集靶点输入FunRich软件进行富集分析,得到生物过程13个、细胞组分37个、分子功能15个及生物通路319条。分子对接显示6种活性成分均与MAPK3有较强的结合力。结论:六味地黄丸治疗抑郁症具有多通路、多成分、多靶点的特点。Objective:To investigate the mechanism of Liuwei Dihuang Wan in the treatment of depression by using network pharmacology and molecular docking technology.Methods:The traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP) was used to retrieve the chemical constituents of Liuwei Dihuang Pills.TCMSP database,PubChem database,BABEL software,SwissTargetPrediction platform,and SEA platform were used to predict medicine active ingredient targets.DisGeNET database was used to obtain targets of depression.The Venn Diagram platform was used to map the relevant targets of the active components of Liuwei Dihuang Pills and the targets of depression diseases,and the potential targets of Liuwei Dihuang Pills in the treatment of depression were obtained.The potential targets of Liuwei Dihuang Pill in the treatment of depression were entered into the STRING database to obtain the protein interaction relationship,and the results were entered into Cytoscape 3.2.1 software to construct a PPI network to screen out key targets.Then import the potential targets and related active ingredients of Liuwei Dihuang Pills into Cytoscape 3.2.1 software,build a network diagram of "medicine active ingredients-potential targets",and screen out the key ingredients.The potential targets were entered into FunRich software for enrichment analysis.Using DockThor software,the target protein with the highest median value in the PPI network was molecularly docked with the active ingredient in the first topological analysis parameter of the six traditional Chinese medicines respectively,and the PyMOL software was used to make a visual picture.Results:It was concluded that 40 active ingredients of Liuwei Dihuang Pills were obtained,and 3706 related targets were obtained.And there are 1478 targets of depression and 38 potential targets of Liuwei Dihuang Pill in the treatment of depression.PPI network topology analysis screened mitogen-activated protein kinase 3(MAPK3) as the first key target.Topological analysis of the netw

关 键 词：六味地黄丸 抑郁症 网络药理学 分子对接 作用机制 

分 类 号：R284.2[医药卫生—中药学]