基于网络药理学探讨苦黄注射液保肝退黄作用机制

Kuhuang injection protecting the liver and alleviating jaundice:exploration of mechanisms based on network pharmacology

目的构建苦黄注射液活性成分-作用靶点网络和蛋白相互作用网络,对靶点涉及的功能和通路进行分析,探讨苦黄注射液保肝退黄的作用机制。方法通过中药系统药理学数据库和分析平台(TCMSP,http://lsp.nwu.edu.cn/tcmsp.php)及相关文献挖掘获取苦黄注射液中苦参、大黄、茵陈、柴胡、大青叶的主要活性成分。利用GeneCard数据库(http://www.genecards.org/)和在线人类孟德尔遗传数据系统(OMIM,http://www.omim.org/)预测和筛选苦黄注射液活性成分对应靶点中与肝炎和黄疸疾病相关靶点。用Cytoscape 3.6.1软件构建活性成分-作用靶点网络,用蛋白质相互作用数据库(STRING,http://string-db.org/)和Cytoscape 3.6.1软件绘制蛋白相互作用网络,用生物学信息注释数据库(DAVID,https://david.ncifcrf.gov/)对靶点进行基因本体(GO)及京都基因与基因组百科全书(KEGG)通路分析。结果筛选得到苦黄注射液活性成分16个,共获得85个作用靶点。网络分析结果表明,苦黄注射液主要涉及细胞过程、代谢过程、对刺激应答的生物过程。靶点通路分析结果显示,苦黄注射液保肝作用的靶点主要涉及丝裂原活化蛋白激酶(MAPK)、Toll样受体、p53、神经营养因子等信号通路。结论苦黄注射液保肝退黄作用具有多成分、多靶点、多通路的特点,其可能通过调节MAPK、Toll样受体、p53、神经营养因子等相关通路发挥作用。

Objective To explore the mechanism of Kuhuang injection in protecting the liver and alleviating jaundice by establishing the active components-target network and protein interaction network and analyzing the functions and pathways.Methods The main active components of Kuhuang injection were obtained through traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP)and related literatures.The targets to treat hepatitis and jaundice of the active components of Kuhuang injection were predicted and screened by GeneCard and online Mendelian inheritance in man(OMIM).Cytoscape 3.6.1 software was used to construct the active component-target network,and STRING database and Cytoscape 3.6.1 software were used to construct the protein interaction network.Gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)pathways involved in the targets were analyzed using the database for annotation,visualization and integrated discovery(DAVID).Results The results showed that 16 active components of Kuhuang injection were screened and 85 targets were obtained.The results of network analysis showed that cellular processes,metabolic processes,and processes in response to stress were mainly involved in the effects of Kuhuang injection against hepatitis and jaundice.The results of target pathway analysis showed that the targets of Kuhuang injection for hepatitis and jaundice were mainly involved in mitogen-activated protein kinase(MAPK),Toll-like receptor,p53,neurotrophin and other signaling pathways.Conclusion The anti-hepatitis and jaundice effects of Kuhuang injection are characterized by multiple components,multiple targets and multiple pathways,which might be through regulating MAPK,Toll-like receptor,p53,neurotrophin and other related pathways.