摘要
目的基于网络药理学探讨茵陈治疗急性胰腺炎(AP)的作用机制。方法利用中药系统药理学数据库与分析平台获取茵陈有效活性成分及其作用靶点,通过GeneCards®数据库和OMIM®数据库获取AP相关靶点,取两者交集得到茵陈治疗AP的相关靶点,使用Perl软件和Cytoscape 3.8.0软件构建“中药-活性成分-基因靶点-疾病”网络图,使用STRING数据库构建蛋白-蛋白相互作用(PPI)网络图,借助R语言进行基因本体论(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。结果共筛选出13个茵陈有效活性成分,包括柳穿鱼黄素、3-[2,3-二氢-2-(2-羟基-1-甲基乙基)-7-(3-甲基-2-丁烯基)苯并呋喃-5-基]丙烯酸、β-谷甾醇、茵陈黄酮、异茵陈蒿黄酮等。共获得茵陈治疗AP相关靶点81个。“中药-活性成分-基因靶点-疾病”网络图显示,在活性成分类节点中,槲皮素、异鼠李素、β-谷甾醇及3′,4′,5′-三羟基-6,7-二甲氧基黄酮的度值和介数值较高;在靶点类节点中,前列腺素内过氧化物合酶(PTGS)2、热休克蛋白90α家族A类成员1、PTGS1、丝氨酸蛋白酶1的度值和介数值较高。PPI网络图显示茵陈治疗AP的重要靶点蛋白包括丝氨酸/苏氨酸蛋白激酶1(AKT1)、肿瘤坏死因子(TNF)、转录因子AP-1亚基(JUN)、白细胞介素(IL)-6、Caspase-3等。GO功能富集分析结果显示,茵陈治疗AP相关靶点涉及的生物过程主要有DNA结合转录因子结合、RNA聚合酶Ⅱ特异性DNA结合转录因子结合、泛素样蛋白连接酶结合等;KEGG通路富集分析结果显示,茵陈治疗AP相关靶点主要与脂质与动脉粥样硬化、流体剪切应力与动脉粥样硬化、乙型肝炎、卡波西肉瘤相关疱疹病毒感染、IL-17信号通路等信号通路有关。结论茵陈中的β-谷甾醇、茵陈黄酮、柳穿鱼黄素等有效活性成分可能通过IL-17信号通路、TNF信号通路等信号通路,作用于AKT1、TNF、JUN等关键靶点而起到治疗AP的作用。
Objective To explore the mechanism of Artemisiae scopariae for the treatment of acute pancreatitis(AP)based on network pharmacology.Methods The effectively active components and their effect targets were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,and the targets related to AP were acquired from the databases of GeneCards®and OMIM®,then the related targets of treating AP by Artemisiae scopariae were obtained by acquiring the intersection of the two.The network chart of Traditional Chinese Medicine-active components-gene targets-disease was established by using Perl software and Cytoscape 3.8.0 software.The protein-protein interaction(PPI)network chart was established by employing STRING database.The Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed by R language.Results A total of 13 effectively active components were screened out,including 4′-methylcapillarisin,artepillin A,β-sitosterol,areapillin,and isoarcapillin,etc.A total of 81 related targets of treating AP by Artemisiae scopariae were obtained.The network chart of Traditional Chinese Medicine-active components-gene targets-disease revealed that in the nodes of active components,the degree value and betweenness value of quercetin,isorhamnetin,β-sitosterol,and eupalitin were relatively high,and in the nodes of targets,the degree value and betweenness value of prostaglandin-endoperoxide synthase(PTGS)2,heat shock protein 90 alpha family class A member 1,PTGS1,and serine protease 1 were relatively high.The PPI network chart revealed that the crucial target proteins contained serine/threonine protein kinase 1(AKT1),tumor necrosis factor(TNF),transcription factor AP-1 subunit(JUN),interleukin(IL)-6,and Caspase-3,etc.The results of GO functional enrichment analysis revealed that the related targets of treating AP by Artemisiae scopariae mainly involved the biological processes in terms of DNA binding transcription factors binding,RNA polymeraseⅡspecific DNA binding transcription factors binding,ubiquitin-like protein ligase binding,etc.The results of KEGG pathway enrichment analysis implied that the related targets of treating AP by Artemisiae scopariae was mainly related with signaling pathways with respect to lipids and atherosclerosis,fluid shear stress and atherosclerosis,hepatitis B,Kaposi sarcoma-associated herpes virus infection,IL-17 signaling pathway,etc.Conclusionβ-sitosterol,areapillin,4′-methylcapillarisin,and other effectively active components of Artemisiae scopariae may act on key targets in terms of AKT1,TNF and JUN through signaling pathways of IL-17 and TNF,etc.,so as to exert therapeutic effects on AP.
作者
蒙诺
覃颖颖
杨慧莹
唐国都
MENG Nuo;QIN Yingying;YANG Huiying;TANG Guodu(The First College of Clinical Medicine,Guangxi Medical University,Nanning 530021,Guangxi,China;Department of Gastroenterology,the First Affiliated Hospital of Guangxi Medical University,Nanning 530021,Guangxi,China)
出处
《广西医学》
CAS
2023年第8期933-938,951,共7页
Guangxi Medical Journal
基金
国家自然科学基金(81970558)。
关键词
急性胰腺炎
茵陈
信号通路
网络药理学
作用机制
Acute pancreatitis
Artemisiae scopariae
Signaling pathway
Network pharmacology
Mechanism
