基于网络药理学和分子对接分析连朴饮治疗新型冠状病毒肺炎伴胃肠道症状的作用机制  

Action Mechanism Analysis of Lianpo Drink in Treatment of COVID-19 with Gastrointestinal Symptoms Based on Network Pharmacology and Molecular Docking

作　　者：王琳 郑福增 WANG Lin;ZHENG Fuzeng(College of Orthopedics and Traumatology,Henan University of Chinese Medicine,Zhengzhou Henan China 450046;The Second Affiliated Hospital to Henan University of Chinese Medicine/Henan Provincial Hospital of Chinese Medicine,Zhengzhou Henan China 450002)

机构地区：[1]河南中医药大学骨伤学院,河南郑州450046 [2]河南省中医院/河南中医药大学第二附属医院,河南郑州450002

出　　处：《中医学报》2022年第9期1947-1953,共7页Acta Chinese Medicine

基　　金：国家自然科学基金项目(81804050)。

摘　　要：目的:基于网络药理学和分子对接探讨连朴饮治疗新型冠状病毒肺炎(corona virus disease 2019,COVID-19)伴胃肠道症状的作用机制和作用靶点。方法:运用中药系统药理数据库和分析平台(traditional Chinese medicine systems pharmacology,TCMSP)检索连朴饮的有效成分及作用靶点,通过GeneCards、OMIM、TTD、PharmGkb、DrugBank数据库收集疾病相关靶点。借助String数据库和Cytoscape软件构建蛋白质相互作用(protein-protein interaction,PPI)网络,并使用Cytoscape对网络进行拓扑分析,获取核心靶点,通过R语言进行基因本体(gene ontology,GO)功能富集分析、京都基因和基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析,最终将核心基因与主要活性成分进行分子对接验证。结果:本研究预测连朴饮所含中药的有效成分43个,对应靶点197个;拓扑分析得到转录活化蛋白1、白细胞介素-8、环氧合酶2、低氧诱导因子-1等12个核心靶点。KEGG通路富集分析筛选得到连朴饮治疗COVID-19合胃肠道症状154条通路,主要包含脂质和动脉粥样硬化、白细胞介素-17信号通路、糖尿病并发症中的AGE-RAGE信号通路、肿瘤坏死因子信号通路、流体剪切应力与动脉粥样硬化等通路,集中抗炎、抗病毒、调节免疫。分子对接结果表明,活性成分能分别与核心靶点结合,具有较好的亲和力。结论:连朴饮可能通过槲皮素、山柰酚等活性成分作用于STAT1、CXCL8、PTGS2、HIF1A等关键靶点,并通过调节AGE-RAGE信号通路、肿瘤坏死因子信号通路、白细胞介素-17信号通路等相关通路调控体内炎症水平,起到治疗COVID-19治疗胃肠道症状的作用。Objective:To explore the mechanism and targets of Lianpo Drink in the treatment of novel coronavirus disease 2019(COVID-19)with gastrointestinal symptoms based on network pharmacology and molecular docking.Methods:The active ingredients and targets of Lianpo Drink were retrieved using traditional Chinese medicine systems pharmacology(TCMSP),and disease-related targets were collected from GeneCards,OMIM,TTD,PharmGkb,and DrugBank databases.The protein-protein interaction(PPI)network was constructed with the help of String database and Cytoscape software,and Cytoscape was used to analyze the network to obtain the core targets,and the gene ontology(GO)function enrichment was carried out by R language.Analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis,and finally the core genes and the main active components were verified by molecular docking.RESULTS:This study predicted that there are 43 active ingredients of traditional Chinese medicines in Lianpo Drink,corresponding to 197 targets;topological analysis obtained transcriptional activation protein 1,interleukin-8,cyclooxygenase 2,hypoxia-inducible factor-1,etc.12 core targets.KEGG pathway enrichment analysis screened 154 pathways for Lianpuyin in the treatment of COVID-19 combined with gastrointestinal symptoms,mainly including lipid and atherosclerosis,interleukin-17 signaling pathway,and AGE-RAGE signaling in diabetic complications pathway,tumor necrosis factor signaling pathway,and fluid shear stress and atherosclerosis pathways,focusing on anti-inflammatory,antiviral,and immune regulation.Molecular docking results showed that the active ingredients could bind to the core targets with good affinity.Conclusion:Lianpo Drink may act on key targets such as STAT1,CXCL8,PTGS2,HIF1A through active components such as quercetin and kaempferol,and regulate AGE-RAGE signaling pathway,tumor necrosis factor signaling pathway,interleukin-17 signaling pathway and other related pathways regulate the level of inflammation in the body and play a role i

关 键 词：连朴饮 新型冠状病毒肺炎 胃肠道症状 网络药理学 分子对接 

分 类 号：R285[医药卫生—中药学]