基于网络药理学和分子对接技术探讨大黄-黄连治疗肝豆状核变性的作用机制

A study on the mechanism of Dahuang-Huanglian in the treatment of hepatolenticular degeneration based on network pharmacology and molecular docking technology

目的:应用网络药理学探讨清热利湿药对大黄-黄连治疗肝豆状核变性的作用机制。方法:使用中药系统药理学数据库分析平台(TCMSP)对大黄-黄连有效成分和作用靶点进行筛选,使用GeneCards数据库纳入肝豆状核变性疾病靶点,取二者交集靶点并绘制韦恩图;利用STRING数据库获取蛋白质-蛋白质相互作用关系,并通过CytoScape 3.9.1软件构建蛋白质-蛋白质相互作用网络图,筛选出大黄-黄连治疗肝豆状核变性的核心靶点;利用DAVID数据库进行关键靶点基因本体论(GO)和京都基因与基因组百科全书(KEGG)功能富集分析;通过AutoDock软件进行分子对接,由PyMol软件进行可视化处理。结果:共检索得到槲皮素、大黄酸、β-谷甾醇等19个有效成分,筛选出228个大黄-黄连治疗肝豆状核变性的潜在作用靶点,经蛋白质-蛋白质相互作用网络拓扑分析筛选出细胞肿瘤蛋白p53(Tumor Protein p53,TP53)、表皮生长因子受体(Epidermal Growth Factor Receptor,EGFR)、白细胞介素(Interleukin,IL)-6、丝氨酸/苏氨酸蛋白激酶1(Akt Serine/Threonine Kinase 1,AKT1)及IL-1B等39个核心靶点,GO功能富集分析到1002个生物学过程、108个细胞组分及202个分子功能;KEGG信号通路富集分析获得188条信号通路。结论:大黄-黄连药对可能通过多个靶点、多条通路治疗肝豆状核变性。

Objective:To explore the mechanism of heat-clearing and dampness-eliminating Dahuang(Radix et Rhizoma Rhei)-Huanglian(Rhizoma Coptidis)in the treatment of hepatolenticular degeneration by network pharmacology and verify it by molecular docking.Methods:The TCMSP database was used to screen the effective components and targets of rhubarb-coptis chinensis,and the GeneCards database was used to include the targets of hepatolenticular degeneration disease.The intersection targets of the two were taken and the Venn diagram was drawn.The STRING database was used to obtain the protein interaction relationship,and the PPI network diagram was constructed by CytoScape 3.9.1 software to screen out the core targets of Dahuang-Huanglian in the treatment of hepatolenticular degeneration.GO and KEGG functional enrichment analysis of key targets was performed using the DAVID database,molecular docking was performed by AutoDock software,and visualization was performed by PyMol software.Results:A total of 19 active ingredients such as quercetin,rhein andβ-sitosterol were retrieved,and 228 potential targets of Dahuang-Huanglian in the treatment of hepatolenticular degeneration were screened out.Thirty-nine core targets such as TP53,EGFR,IL-6,AKT1 and IL-1B were screened out by PPI network topology analysis.GO functional enrichment analysis showed 1002 biological processes,and 108 cell components and 202 molecular functions.KEGG signal pathway enrichment analysis obtained 188 signal pathways.Conclusion:Dahuang�Huanglian may treat hepatolenticular degeneration through multiple targets and multiple pathways,which provides a theoretical basis for subsequent research.