基于网络药理学及分子对接分析雷公藤治疗肾病综合征的作用机制  

Exploring the mechanism of Tripterygium wilfordii Hook F.for nephrotic syndrome based on network pharmacology and molecular docking

作　　者：许剑 Xu Jian(College of Pharmaceutical Sciences,Zhejiang Chinese Medical University,Hangzhou,Zhejinag 321000,China)

机构地区：[1]浙江中医药大学药学院,浙江杭州321000

出　　处：《中国药物与临床》2024年第21期1367-1373,I0001,I0002,F0003,共10页Chinese Remedies & Clinics

摘　　要：目的通过网络药理学及分子对接技术分析雷公藤治疗肾病综合征的作用靶点,为后续该病治疗及药物开发提供理论基础。方法通过中药系统药理学数据库与分析平台(TCMSP)数据库筛选出雷公藤的活性成分及活性靶点;利用PubChem和Swiss Target Prediction数据库将活性成分转化为基因名;通过Disgenet、GeneCards数据库获取肾病综合征的疾病靶点;利用Venny 2.1软件绘制雷公藤与肾病综合征基因的共同靶点韦恩图;应用Cytoscape3.2.1软件构建"雷公藤-主要成分-肾病综合征"交集基因网络图;利用STRING数据库对其作用靶点构建蛋白-蛋白相互作用(PPI)网络分析;使用DAVID数据库对这些靶点进行基因本体(GO)和京都基因与基因组百科全书(KFGG)通路富集分析;利用AutoDockTools软件对核心靶点和雷公藤活性成分进行分子对接。结果筛选得到雷公藤有效活性成分418个,肾病综合征对应靶点2382个,药物-疾病共同作用交集靶点171个。GO功能富集分析显示:有34个核心靶点相互作用关系,其中蛋白激酶B1(Akt1)、白细胞介素(IL)-6、缺氧诱导因子1亚基α(HIF1A)、肿瘤蛋白P53(TP53)与转录激活因子(STAT3)等最为重要,可能是雷公藤治疗肾病综合征的潜在治疗靶点;核心通路有癌症的发病途径、卡波西肉瘤相关疱疹病毒感染、乙型肝炎、癌症中的蛋白聚糖和脂质与动脉粥样硬化等关键通路。分子对接显示:滇南蛇藤碱、山奈酚、异黄腐醇、化合物A和化合物B等5个活性成分与Akt1、IL-6、HIF1A、TP53、STAT3、表皮生长因子受体(EGFR)、肿瘤坏死因子(TNF)、半胱氨酸-天冬氨酸蛋白酶3(CASP3)等8个靶点具有结合潜力,其中以山奈酚与Akt1、TP53、EGFR和CASP3等4个靶点的结合能最低,稳定性最好。结论雷公藤可通过多成分、多靶点、多通路在治疗肾病综合征中发挥作用。ObjectiveTo explore the target Tripterygium wilfordii Hook F.in the treatment of nephropathy syndrome through network pharmacology and molecular docking technology,and to provide a theoretical basis for subsequent disease treatment and drug development.MethodsThe active ingredients and targets of Tripterygium wilfordii Hook F.were screened through the Traditional Chinese Medicine(TCM)systems pharmacology database and analysis platform TCMSP database.The active ingredients were converted into gene names using the PubChem and SwissTarget Prediction databases.Disease targets of nephrotic syndrome were obtained through the Disgenet and GeneCards databases.Wayn diagram of the common target of Tripterygium wilfordii Hook F.and nephrotic syndrome gene using Venny 2.1 software;Software to construct the intersection gene network map of nephrotic syndrome by using Cytoscape3.2.1;Protein interaction(PPI)network analysis was constructed by using the STRING database;These targets were subjected to Gene ontology GO and Kyoto Encyclopedia of Genome and Genome KFGG pathway enrichment analysis using the DAVID database.Molecular docking of core target and active components was performed using AutoDockTools software.ResultsA total of 418 effective active ingredients were screened from Tripterygium wilfordii,2382 corresponding targets for nephrotic syndrome,and 171 intersecting targets for drug-disease interaction.GO functional enrichment analysis showed that there were 34 core target interactions,among which Akt1,IL-6,HIF1A,TP53,and STAT3 were the most important,and may be potential therapeutic targets for the treatment of nephrotic syndrome;The core pathways included cancer pathogenesis,Ka-posi sarcoma-associated herpesvirus infection,hepatitis B,proteoglycans and lipids in cancer,atherosclerosis and other key pathways.Molecular docking showed that five active ingredients,including aconitine,kaempferol,iso-quercetin,triptolides,and triptolides,had binding potential with eight targets,including Akt1,IL-6,HIF1A,TP53,STAT3,EGFR,TNF,a

关 键 词：网络药理学 分子对接模拟 雷公藤 肾病综合征 

分 类 号：R285[医药卫生—中药学]