基于网络药理学与分子对接技术探讨益肝草凉茶解酒保肝的作用机制

王雅芝; 张建永; 段灿灿

doi:10.13386/j.issn1002-0306.2020070092

基于网络药理学与分子对接技术探讨益肝草凉茶解酒保肝的作用机制

Mechanism of Relieving Alcohol and Protecting Liver of Yigancao Herbal Tea Based on Network Pharmacology and Molecular Docking Technology

摘要

摘要: 目的：通过网络药理学方法和分子对接技术，探讨益肝草凉茶解酒保肝的作用机制。方法：利用中药系统药理学分析平台（Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform，TCMSP）、中医药综合数据库（Traditional Chinese Medicines Integrated Database，TCMID）、中药分子机制生物信息学分析工具(A Bioinformatics Analysis Tool for Molecular MechANism of Traditional Chinese Medicine，BATMAN-TCM）、SwissTargetPrediction和TargetNet等数据库，检索益肝草凉茶中9味中药的活性成分及相关靶点；通过比较毒理基因组学数据库（The Comparative Toxicogenomics Database，CTD）、功能关联蛋白网络数据库（Functional Protein Association Networks，STRING）以及蛋白数据库（Universal Protein，Uniprot）数据库获取肝病相关的靶点；通过药物作用靶点及肝病靶点互作筛选益肝草凉茶解酒保肝的靶点，进一步构建解酒保肝靶点的蛋白相互作用网络；通过生物学信息注释数据库（Functional Annotation Bioinformatics Microarray Analysis，DAVID）数据库进行靶点蛋白的基因功能与通路分析；采用Cytoscape软件进行网络构建与分析；借助AutoDock软件，将关键成分与重要靶点进行分子对接验证。结果：本研究共收集到益肝草凉茶的活性成分186个，可作用于298个靶点，其中涉及到肝脏疾病的靶点有78个。预测靶点主要作用于癌症的途径、钙信号通路、神经活性配体-受体相互作用、5-羟色胺能突触、cGMP-PKG信号通路等通路发挥保肝护肝作用。结论：本研究揭示了益肝草凉茶可通过多成分、多靶点、多通路的作用特点调控网络发挥解酒保肝的功效，为其治疗酒精性肝病的研究和临床应用提供科学依据。

Abstract: Objective: To explore the mechanism of relieving alcohol and protecting liver of Yigancao herbal tea by network pharmacology and molecular docking technology. Methods: The active components of 9 traditional Chinese medicines in Yigancao herbal teawere obtained through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Traditional Chinese Medicines Integrated Database (TCMID) and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). The related targets were predicted by Swiss Target Prediction and Target Net databases, while the targets related to liver disease were collected by The Comparative Toxicogenomics Database (CTD), Functional Protein Association Network (STRING) and Uniprot database. The targets of Yigancao herbal tea were screened by drug action target and liver disease target interaction, and the protein interaction network of liver protection target was further constructed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways involved in the targets were analyzed using the Databasefor Annotation, Visualization and Integrated Discovery (DAVID), and the network was constructed and analyzed by Cytoscape software. With the help of Auto Dock software, the key components and important targets were verified by molecular docking. Results: The results showed that 186 active components of Yigancao herbal tea were screened and 298 targets were obtained, including 78 targets related to liver diseases. These targets were mainly involved in Pathways in cancer, Calcium signal pathway, Neuroactive ligand-receptor interaction, Serotonergic synapse, cGMP-PKG signaling pathway and other pathways to protect liver. Conclusion: This study revealled that Yigancao herbal tea could exert the effect of relieving alcohol and protecting liver through the regulation network of multi-components, multi-targets and multi-pathways, which provides a scientific basis for the research and clinical application of Yigancao herbal tea in the treatment of alcoholic liver disease.