基于网络药理学及分子对接技术探究黄连解毒汤治疗脓毒症的分子机制

Molecular Mechanism of the Treatment of Sepsis with Huanglian Jiedu Decoction Based on Network Pharmacology and Molecular Docking

目的:采用网络药理学方法和生物信息学理论,挖掘黄连解毒汤有效成分,预测黄连解毒汤治疗脓毒症的作用机制,为中医治疗该病提供理论依据。方法:利用TCMSP等数据库平台筛选黄连解毒汤有效活性成分。在Gene Card、OMIM及Disgenet数据库中获得脓毒症相关基因,结合疾病靶点及药物活性成分绘制PPI网络,对关键靶点并进行GO、KEGG富集分析以及运用Autodock软件进行关键靶点分子对接研究。结果:通过检索共筛选出黄连解毒汤有效活性成分59个,在此基础上获得206个预测靶点及关键基因;根据基因本体(gene ontology,GO)分析及京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)结果可知,黄连解毒汤作用于该疾病主要涉及细胞因子活化、免疫和炎症相关过程激活等生物进程如肿瘤坏死因子(tumor necrosis factor,TNF)、白细胞介素17(interleukin-17,IL-17)炎症信号通路及晚期糖基化通路(AGEs-RAGE)等。分子对接结果表明药对的活性成分可以对核心靶点(JUN和TNF)发挥调控作用。结论:黄连解毒汤治疗脓毒症作用机制是多层次、多角度的,其主要机制集中在抗炎及氧化应,为研究黄连解毒汤多成分、多靶点治疗脓毒症网络关系提供了新的研究思路。

Objective:To provide theoretical evidence for TCM therapy of sepsis by unearthing the active ingredients of Huanglian Jiedu Tang and predicting the mechanism of treating sepsis with the decoction with network pharmacology and bioinformatics.Methods:The active ingredients of Huanglian Jiedu Tang were prepared by screening in TCMSP.Gene Card,OMIM and Disgenet databases were used to obtain sepsis-related genes,and PPI network was mapped by combining with disease targets and active ingredients of the drug,to carry out GO and KEGG enrichment analysis for key targets,and to conduct the study of molecular docking of key targets using Autodock software.Results:Through searching,there were 59 active ingredients of Huanglian Jiedu Tang,involving 206 predicted targets and key genes;the results of GO analysis and KEGG presented that the decoction acting on sepsis mainly referred to the biological processes such as the activation and immunity of cytokines,the activation of inflammation-related processes,including TNF,IL-17 and AGEs-RAGE.The results of molecular docking indicated that the active ingredients of the drug pairs could play the regulatory role in core targets(JUN and TNF).Conclusion:Huanglian Jiedu Tang could treat sepsis from multi-level and multi-angle,and its main mechanism focuses on anti-inflammation and oxidative stress,which could provide new research thinking for the study on treating sepsis with the decoction from multi-component and multi-target.