摘要
目的基于网络药理学和分子对接方法探究泽泻三萜成分抗肝纤维化的潜在作用机制。方法根据数据库筛选及文献调研选取以泽泻三萜中8种活性成分为研究对象,利用Swiss Target Prediction网络平台预测其作用靶点;通过GeneCards、OMIM数据库获取与肝纤维化有关的靶点,借助Cytoscape 3.7.2软件构建“活性成分-抗肝纤维化靶点”网络图,并通过度值筛选核心成分;使用String平台进行蛋白相互作用(protein-protein interaction,PPI)分析,结合Cytoscape 3.7.2软件构建PPI网络图,通过度值、节点紧密度、节点介度筛选关键靶点;采用DAVID数据库对泽泻三萜抗肝纤维化的作用靶点进行基因本体(gene ontology,GO)功能和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析;使用AutoDock软件对核心成分与关键靶点进行分子对接;考察乙酰泽泻醇C对油酸和棕榈酸诱导的小鼠正常肝细胞(NCTC-1469)上清液一氧化氮(nitric oxide,NO)水平的影响。结果筛选出泽泻三萜中8种活性成分包括24-乙酰泽泻醇A、泽泻醇B、乙酰泽泻醇B、16β-甲氧基乙酰泽泻醇B、泽泻醇C、乙酰泽泻醇C、泽泻内酯D、25-甲氧基泽泻醇F,预测得到35个抗肝纤维化靶点,4个核心成分包括乙酰泽泻醇B、16β-甲氧基乙酰泽泻醇B、泽泻醇C、乙酰泽泻醇C,4个关键靶点包括蛋白激酶Cα(protein kinase Cα,PRKCA)、丝裂原活化蛋白激酶1(mitogen-activated protein kinase 1,MAPK1)、磷酯酰肌醇-3激酶催化亚基γ(phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunitγ,PIK3CG)、MAPK8;基因富集分析得到GO功能条目142个、通路69条(P<0.05);分子对接结果显示,核心成分与关键靶点均有较强的潜在结合能力;网络药理学分析显示,泽泻三萜成分主要通过作用于脂多糖反应、凋亡等生物过程及肿瘤坏死因子(tumor necrosis factor,TNF)、磷脂酰肌醇-3激酶(phosphatidylinositol 3-kinase,PI
Objective To explore the potential mechanism of triterpenoids from Alisma orientalis against liver fibrosis based on network pharmacology and molecular docking method.Methods According to database screening and literature investigation,eight active components from A.orientalis triterpenes were selected as research objects,and their action targets were predicted by Swiss Target Prediction network platform,targets related to liver fibrosis were obtained through GeneCards and OMIM databases,and“active ingredients-anti-liver fibrosis targets”network was constructed by Cytoscape 3.7.2 software;Protein-protein interaction(PPI)analysis was carried out by String platform,PPI network diagram was constructed by Cytoscape 3.7.2 software,key targets were screened by degree value,node tightness and node degree.Gene ontology(GO)function and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis on anti-liver fibrosis targets of A.orientalis triterpenes were carried out by DAVID database;AutoDock software was used for molecular docking between core components and key targets;Effect of acetyl alisol C on nitric oxide(NO)levels in supernatant of NCTC-1469 cells induced by oleic acid and palmitic acid was investigated.Results Eight active components of A.orientalis triterpenes including alisol A 24-acetate,alisol B,alisol B monoacetate,16β-methoxyalisol B monoacetate,alisol C,alisol C monoacetate,alisolides D and 25-O-methyalisol F were obtained.Thirty-five anti-liver fibrosis targets were predicted,four core components including alisol B monoacetate,16β-methoxy alisol B monoacetate,alisol C and alisol C monoacetate and four key targets including protein kinase Cα(PRKCA),mitogen-activated protein kinase 1(MAPK1),phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunitγ(PIK3CG)and MAPK8 were selected.GO enrichment analysis revealed 142 GO functional entries and 69 pathways(P<0.05).Results of molecular docking showed that core components displayed strong binding abilities with key targets respective
作者
江雯
叶晨
胡熳
刘钰偲
张艳
梁继超
陈勇
JIANG Wen;YE Chen;HU Man;LIU Yu-cai;ZHANG Yan;LIANG Ji-chao;CHEN Yong(National&Local Joint Engineering Resarch Center of High-throughput Drug Screening Technology,Hubei Key Laboratory ofBiotechnology of Chinese Traditional Medicine,State Key Laboratory of Biocatalysis and Enzyme Engineering,School of LifeSciences,Hubei University,Wuhan 430062,China)
出处
《中草药》
CAS
CSCD
北大核心
2022年第4期1100-1111,共12页
Chinese Traditional and Herbal Drugs
基金
大学生创新创业训练计划项目(X202010512076,X202010512072)。
