金银花治疗登革热的网络药理学分析

Network Pharmacological Analysis of Honeysuckle in the Treatment of Dengue Fever

目的 基于网络药理学方法探讨金银花治疗登革热的活性成分及作用机制。方法 运用TCMSP、UniProt数据库筛选金银花的活性成分及其作用靶点;通过Genecards、CTD和DisGeNET数据库检索登革热疾病相关靶点;对金银花活性成分作用靶点与登革热疾病相关靶点取交集(共同靶点),即得金银花治疗登革热的潜在作用靶点;采用Cytoscape 3.8.2软件构建金银花治疗登革热的“活性成分-作用靶点”网络;对共同靶点进行蛋白互作(PPI)网络分析、MCODE及KEGG通路富集分析。结果 共得到金银花活性成分12种,活性成分作用靶点209个,登革热疾病相关靶点3 374个,共同靶点124个。关键活性成分包括槲皮素、木犀草素、山柰酚和β-胡萝卜素等;核心靶点包括ALB、AKT1、TP53、IL6、TNF、VEGFA等;主要生物学过程包括外源性刺激引发自身免疫、氧化应激反应、细胞凋亡等;关键KEGG通路包括IL-17信号通路、TNF信号通路、PI3K-Akt信号通路、C型凝集素受体信号通路、MAPK信号通路和Toll样受体信号通路等。结论 金银花治疗登革热具有多成分、多靶点、多通路的特点,主要与干预炎症反应和免疫调控途径相关。

Objective To explore the active ingredients and underlying mechanisms of honeysuckle in the treatment of dengue fever based on the network pharmacological approach. Methods TCMSP and UniProt databases were used to screen the active ingredients of honeysuckle and their targets;Genecards,CTD and DisGeNET databases were used to search for dengue disease-related targets;the intersection of active ingredient targets of honeysuckle and dengue disease-related targets(common targets)was taken to obtain the potential targets of honeysuckle for dengue;Cytoscape 3.8.2 software was used to construct the "active ingredients-target networks" of honeysuckle for dengue;protein-protein interaction(PPI)network analysis,MCODE and KEGG pathway enrichment analysis were performed on the common targets. Results A total of 12 active ingredients of honeysuckle were obtained, with 209 active ingredient action targets and 3 374 dengue disease-related targets, for a total of 124 targets. The key active ingredients included quercetin,lignan,kaempferol and β-carotene,etc.;the core targets included ALB,AKT1,TP53, IL6, TNF, VEGFA, etc.;the main biological processes included autoimmunity triggered by exogenous stimuli,oxidative stress response,apoptosis,etc.;the key KEGG pathways included IL-17 signaling pathway,TNF signaling pathway,PI3K-Akt signaling pathway,C-type lectin receptor signaling pathway,MAPK signaling pathway and Toll-like receptor signaling pathway,etc. Conclusion The treatment of dengue fever with honeysuckle has characteristics of multi-component, multi-target and multi-pathway, mainly related to intervention in the inflammatory response and immune modulation pathways.