枳椇子抗肝纤维化作用网络药理学研究  

Effect of Hovenia Dulcis for Anti-Hepatic Fibrosis Based on Network Pharmacology

作　　者：吾斯曼·艾海提[1] 艾则孜江·艾尔肯 Wusiman AIHAITI;Aizezijiang AIERKEN(Department of Pharmacy,The First Affiliated Hospital of Xinjiang Medical University,Urumqi,Xinjiang,China 830054)

机构地区：[1]新疆医科大学第一附属医院药学部,新疆乌鲁木齐830054

出　　处：《中国药业》2022年第16期36-40,共5页China Pharmaceuticals

基　　金：新疆维吾尔自治区自然科学基金[2020D01C165]。

摘　　要：目的探讨枳椇子抗肝纤维化的作用机制。方法通过中药系统药理学数据库与分析平台(TCMSP)获取枳椇子的活性成分,构建活性成分库。利用GeneCards和人类孟德尔遗传数据库(OMIM)获取肝纤维化的潜在靶点,利用Venny平台与枳椇子活性成分靶点取交集,通过Cytoscape软件构建成分-靶点网络,并根据节点度值筛选得到核心成分。将共有靶点导入String构建蛋白-蛋白相互作用(PPI)网络,并根据节点度值筛选得核心靶点;采用R语言软件进行基因本体论(GO)功能富集分析及京都基因与基因组百科全书(KEGG)通路富集分析。结果共获得活性成分7个,对应靶点183个,与肝纤维化共同靶点166个;枳椇子中槲皮素、山柰酚、柚皮素等6个成分为抗肝纤维化的核心成分;PPI网络分析得到AKT1,JUN,MAPK3等10个核心靶点;GO功能富集分析主要涉及金属离子应答、药物应答及化学刺激细胞应答等生物学过程,KEGG通路富集分析主要涉及肿瘤坏死因子(TNF)、白细胞介素17(IL-17)及晚期糖基化终末产物及其受体等信号通路。结论枳椇子可能通过槲皮素、山柰酚及柚皮素等多种成分,作用于AKT1,JUN及MAPK3等多个靶点,通过TNF、IL-17及AGE-RAGE等信号通路发挥抗肝纤维化作用。Objective To investigate the mechanism of Hovenia dulcis for anti-hepatic fibrosis based on network pharmacology.Methods The active components of Hovenia dulcis were obtained through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the active component library was constructed.The potential targets of hepatic fibrosis were obtained through the GeneCards and Online Mendelian Inheritance in Man(OMIM).The intersection of liver fibrosis targets and the active component targets of Hovenia dulcis was obtained by the Venny platform.The component-target network was constructed by Cytoscape software,and the key components were screened according to node degree value.The common targets were imported into the String database to construct the protein-protein interaction(PPI)network,and the key target was screened according to the node degree value.Gene Ontology(GO)function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were conducted through the R language software.Results Seven active components were obtained,with 183 corresponding targets and 166 common targets with hepatic fibrosis.Six components of Hovenia dulcis such as quercetin,kaempferol and naringenin were the key components for anti-hepatic fibrosis.PPI network analysis showed that 10 targets such as AKT1,JUN,MAPK3 were the key targets.GO function enrichment analysis mainly involved biological processes such as metal ion response,drug response and chemical stimulated cell response.KEGG pathway enrichment analysis mainly involved signal pathways such as tumor necrosis factor(TNF),interleukin-17(IL-17),advanced glycation end products and their receptors(AGE-RAGE).Conclusion Hovenia dulcis may play an anti-hepatic fibrosis role through acting on AKT1,JUN,MAPK3 and other targets by quercetin,kaempferol,naringin and other components,and acting on multiple signal pathways such as TNF,IL-17 and AGE-RAGE.

关 键 词：枳椇子 肝纤维化 作用机制 网络药理学 

分 类 号：R975.5[医药卫生—药品]