黄连解毒汤治疗脓毒症的网络药理学研究

Mechanism of Huanglian Jiedu Decoction in the Treatment of Sepsis Based on Network Pharmacology

目的:探索黄连解毒汤治疗脓毒症的核心作用靶点、主要活性成分及作用机制。方法:在中药系统药理学数据库与分析平台(TCMSP)以黄连、黄芩、黄柏、栀子为关键词分别检索,按照口服生物利用度(OB)≥30%,类药性(DL)≥0.18的条件筛选,获得黄连解毒汤各中药的活性成分及其作用靶点;通过在线人类孟德尔遗传数据库(OMIM)、GeneCards、治疗靶点数据库(TTD)检索脓毒症的疾病靶点;将预测到的成分及其疾病靶点运用Cytoscape软件进行中药-成分-疾病-靶点网络构建及分析,筛选核心靶点及主要活性成分,通过STRING数据库结合Cytoscape软件绘制蛋白质-蛋白质相互作用(PPI)网络并进行网络拓扑学分析,通过R语言运行后对核心靶点进行基因本体(GO)分析和京都基因和基因组百科全书(KEGG)通路注释分析,设定阈值P<0.05,Q<0.05,筛选具有显著性差异的生物过程及信号通路。结果:筛选出黄连解毒汤78个成分和841个药物靶点;这些共同靶点涉及147条生物过程包括TNF信号通路、趋化因子信号通路、HIF-1信号通路、细胞凋亡通路等代谢通路,内分泌抵抗等与内分泌系统相关的通路。结论:黄连解毒汤中小檗碱、槲皮素、山柰酚等多种成分协同作用于AGE-RAGE信号通路、TNF信号通路等,初步揭示了其在治疗脓毒症时的多成分、多途径、多靶点协同作用的复杂机制过程,为未来实验验证奠定了理论基础。

Objective:To explore the core targets,main active components and mechanism of Huanglian Jiedu Decoction in the treatment of sepsis.Methods:The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)was searched,with黄连(Rhizoma Coptidis),黄芩(Radix Scutellariae),黄柏(Cortex Phellodendri),and栀子(Fructus Gardeniae)as keywords.According to bioavailability(OB)≥30%and drug-likeness(DL)≥0.18,the active components and targets of each Chinese medicinal material in Huanglian Jiedu Decoction were obtained.Online Mendelian Inheritance in Man(OMIM),GeneCards,and Therapeutic Target Database(TTD)were used to screen the targets of sepsis.Then the obtained predicted components and disease targets were input in Cytoscape to construct the network of Chinese medicinal material-components-disease-targets,and the core targets and main active components were screened.The protein protein interaction(PPI)network was plotted via STRING combined with Cytoscape and topological analysis was performed.After R language running,GO analysis and KEGG pathway annotation analysis were conducted on the core targets,with the thresholds of P<0.05 and Q<0.05,to screen the biological processes and signaling pathways with significant differences.Results:A total of 78 components and 841 targets of Huanglian Jiedu Decoction were screened,and 147 biological pathways were involved,including metabolic pathways such as tumor necrosis factor(TNF),chemokine,hypoxia-inducible factor 1(HIF-1),and apoptosis signaling pathways,and pathways related to the endocrine system such as AGE-RAGE signaling pathway in diabetic complications and endocrine resistance.Conclusion:Berberine,quercetin,kaempferol and other components in Huanglian Jiedu Decoction synergistically acted on the AGE-RAGE signaling pathway,TNF signaling pathway,etc.,which preliminarily revealed the complex multi-component,multi-pathway and multi-target synergistic mechanism of Huanglian Jiedu Decoction in the treatment of sepsis,and laid a theoretical foundation for future experimental verification.