基于网络药理学与分子对接法探讨吴茱萸汤治疗偏头痛的作用机制

A study on the action mechanism of the Wuzhuyu decoction on migraine based on network pharmacology and molecular docking

目的:采用网络药理学方法筛选吴茱萸汤的活性成分,预测其治疗偏头痛的潜在作用靶标和信号通路,进一步探究其作用机制。方法:通过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)筛选吴茱萸汤的活性成分和候选靶标,利用Gene Cards数据库和OMIM数据库去重、合并,预测吴茱萸汤的相关靶标,筛选吴茱萸汤的活性成分治疗疾病的潜在作用靶标;利用Cytoscape软件创建出“疾病-药物-成分-靶点”网络;凭借蛋白质相互作用数据库(STRING)创建潜在靶标蛋白的蛋白质-蛋白质相互作用网络,并找到吴茱萸汤治疗偏头痛的关键基因蛋白;使用Metascape对吴茱萸汤治疗偏头痛的潜在作用靶标进行生物学功能和代谢通路分析;利用Auto Tools软件将核心成分和靶点蛋白进行分子对接,并用Pymol软件对结合能最低的分子进行可视化。结果:吴茱萸汤中共筛选出72种有效活性成分,根据靶点预测技术预测出相关靶点201个;偏头痛与吴茱萸汤有106个共同靶点基因;蛋白质-蛋白质相互作用网络中关键靶点蛋白主要有白细胞介素(Interleukin,IL)-6、肉瘤病毒17癌基因同源物(JUN)、FBJ鼠科骨肉瘤病毒癌基因同源物(FOS)、周期蛋白D1、IL-8等;基因本体论(GO)富集分析主要涉及有毒物质的反应、对伤害的反应、血液循环、活性氧代谢过程等;京都基因与基因组百科全书(KEGG)通路分析主要涉及缺氧诱导因子-1信号通路、丝裂原活化蛋白激酶(Mitogen-activated Protein Kinase,MAPK)信号通路、环磷酸腺苷(Cyclic Adenosine Monophosphate,c AMP)信号通路等信号通路;分子对接结果表明核心成分和靶点蛋白的亲和力较好。结论:本研究采用网络药理学方法初步预测了吴茱萸汤治疗偏头痛的可能机制,为后续进一步研究提供思路。

Objective:To screen the active components of the Wuzhuyu decoction(吴茱萸汤)by network pharmacology method,in order to predict its potential targets and signal pathways in the treatment of migraine,and further explore its action mechanism.Methods:The active ingredients and candidate targets of the Wuzhuyu decoction were screened by TCMSP.The related data was deduplicated and merged by GeneCards database and OMIM database to predict the related targets of the Wuzhuyu decoction,and the potential targets of the active ingredients of the Wuzhuyu decoction on diseases were screened.The network of“disease-medicine-component-target”was established by Cytoscape software.With the help of protein interaction database(STRING),the PPI network of potential target proteins was established,and the key gene proteins of the Wuzhuyu decoction on migraine were found.The biological function and metabolic pathway of potential targets of the Wuzhuyu decoction on migraine were analyzed by Metascape software.The molecular docking of core components and target proteins was performed by Auto Tools software.Pymol software was used to visualize the molecules with the lowest binding energy.Results:A total of 72 active ingredients were screened out from the Wuzhuyu decoction,and 201 related targets were predicted according to target prediction technology.There were 106 common target genes between migraine and the Wuzhuyu decoction.The key target proteins in PPI network mainly included IL-6,JUN,FOS,CCND1,IL-8,etc..The GO enrichment analysis mainly involved the response to toxic substances,response to injury,blood circulation,reactive oxygen metabolism and so on.The KEGG pathway analysis mainly involved hypoxia inducible factor-1 signal pathway,MAPK signal pathway,cAMP signal pathway and so on.The results of molecular docking showed that the affinity between core components and target proteins was good.Conclusion:This study preliminarily predicted the possible action mechanism of the Wuzhuyu decoction on migraine by means of network pharmacology,and provided more ideas for further research.