基于网络药理学探讨茵栀黄口服液治疗黄疸的作用机制研究

Mechanism of Yinzhihuang Oral Liquid in Treatment of Jaundice Based on Network Pharmacology

目的:基于网络药理学方法构建茵栀黄口服液成分-靶点-通路的相互作用网络,探究其治疗黄疸可能的分子机制。方法:利用中药系统药理学数据库与分析平台(TCMSP)获取茵栀黄口服液4种成分-茵陈、栀子、黄芩、金银花的有效活性成分,并对潜在靶点进行预测,进而绘制药物有效活性成分韦恩图及化合物-靶点网络图,通过人类孟德尔遗传数据库(OMIM)、GeneCards及Drugbank数据库筛选出黄疸相关靶点,与获得的药物预测靶点取交集,再将交集靶点导入STRING数据库及Cytoscape 3.7.2,得到蛋白质-蛋白质相互作用(PPI)网络图;通过Metascape对关键靶点进行基因本体(GO)富集分析和京都基因和基因组百科全书(KEGG)富集分析。结果:茵栀黄口服液的4种成分-茵陈、栀子、黄芩、金银花在TCMSP数据库中共检索到530个化学成分,根据口服生物利用度(OB)和类药性(DL)共筛选出87个活性成分,得到作用于黄疸的靶点共233个,通过与疾病数据库筛选出黄疸相关靶点取交集,获得交集靶点122个,GO功能分析集中在对细胞凋亡、细胞因子受体结合的调控,对多种蛋白激酶活性的调节等方面,KEGG通路分析得到T细胞受体信号通路、IL-17信号通路、PI3K-AKT信号通路、核因子κB信号通路等通路。结论:本研究结果显示茵栀黄口服液治疗黄疸具有多成分、多靶点的作用特点,并预测了可能的作用机制,为后期实验研究提供了理论依据。

Objective:To construct a component-target-pathway network and decipher the mechanism of Yinzhihuang Oral Liquid in the treatment of jaundice based on network pharmacology.Methods:The active components of the four herbal medicines(Artemisiae Scopariae Herba,Gardeniae Fructus,Scutellariae Radix,and Lonicerae Japonicae Flos)in Yinzhihuang Oral Liquid were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),on the basis of which the potential targets were predicted.Venn diagram and component-target network were established.The jaundice-related targets were obtained from OMIM,GeneCards,and Drugbank.The common targets shared by the active components and jaundice were imported into STRING and Cytoscape 3.7.2 to establish the protein-protein interaction(PPI)network.Metascape was employed to perform gene ontology(GO)annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment of the key targets.Results:A total of 530 chemical components of Yinzhihuang Oral Liquid were retrieved from TCMSP.According to the oral bioavailability(OB)and drug likeness(DL),87 active components were screened out.A total of 233 targets associated with jaundice were screened out.The active components and jaundice shared 122 common targets.The enriched GO terms indicated that the common targets were mainly involved in the regulation of cell apoptosis,cytokine-receptor binding,and the activities of protein kinases.The KEGG pathway enrichment predicted that the targets mainly participated in the T cell receptor,IL-17,PI3K-AKT,and NF-κB signaling pathways.Conclusion:Yinzhihuang Oral Liquid treats jaundice via multiple components and multiple targets.The possible mechanism of action predicted in this study provides a theoretical basis for later experimental research.