黄芩防治糖尿病肾病的药效物质基础及其作用机制探索

Pharmacodynamic Material Basis and Machanism of Scutellaria Baicalensis for Treatment of Diabetic Nephropathy

目的通过网络药理学及分子对接方法研究黄芩防治糖尿病肾病(diabetic nephropathy,DN)的潜在物质基础与分子机制。方法依据中医药系统药理学数据库分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)筛选黄芩有效化学成分及靶点信息,检索相关疾病数据库得到DN对应基因,并通过维恩图筛选黄芩在治疗DN中的潜在靶点。利用Cytoscape软件构建黄芩活性成分、作用靶点网络图。String平台进行蛋白质相互作用(protein-protein interaction,PPI)网络分析,通过DAVID数据库进行功能富集和途径富集分析,使用AutoDock vina软件进行分子对接。结果获得黄芩防治DN的相关活性成分30个,潜在防治DN靶点53个。网络分析结果显示,丝氨酸/苏氨酸蛋白激酶1(serine/threonine-protein kinase 1,Akt1)、白细胞介素6(interleukin 6,IL-6)和肿瘤坏死因子(tumor necrosis factor,TNF)可能是黄芩防治DN的关键靶点。富集分析进一步表明,脂多糖应激、蛋白质磷酸化正调控等生物过程和胰岛素抵抗(insulin resistance,IR)、磷脂酰肌醇3激酶/蛋白激酶B(phosphatidylinositol 3-kinase/protein kinase B,PI3K/Akt)、Toll样受体(Toll-like receptor,TLR)等信号通路与黄芩防治DN密切相关。分子对接结果提示主要成分汉黄芩素、黄芩素、金合欢素与核心靶点稳定结合。结论通过网络药理学挖掘出黄芩活性成分防治DN的可能靶点及信号转导机制,为黄芩在DN的临床应用提供了理论基础。

Objective To examine the potential components basis and molecular mechanism of the Scutellaria baicalensis preventing diabetic nephropathy(DN)by the network pharmacology and molecular docking.Methods The effective chemical constituents and target information of Scutellaria baicalensis was screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),DN corresponding genes were obtained by searching databases of relevant diseases,and the potential targets for Scutellaria baicalensis in treating DN were screened by Venn diagram.The network diagrams of Scutellaria baicalensis active component and targets were constructed by Cytoscape software.Protein-protein interaction(PPI)network was analyzed by String platform.Functional enrichment and pathway enrichment analysis were conducted by the DAVID database.Molecular docking was carried out by the AutoDock vina program.Results Thirty active ingredients of Scutellaria baicalensis were screened,and fifty-three target genes for treatment of DN were identified.Serine/threonine-protein kinase 1(Akt1)、interleukin6(IL-6)and tumor necrosis factor(TNF)may be regarded as key targets of Scutellaria baicalensis for the treatment of DN based on network analysis.Enrichment analysis further showed that biological processes such as lipolysaccharides stress,positive regulation of protein phosphorylation,insulin resistance(IR),phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt),Toll-like receptor(TLR)and other signaling pathways were closely related to Scutellaria baicalensis against DN.Molecular docking results indicated that main components wogonin,baicalein and acacetin bound well to all key targets.Conclusion The possible targets and signal transduction mechanism of Scutellaria baicalensis active ingredients against DN are explored by network pharmacology,and provides a theoretical basis for the application of Scutellaria baicalensis in clinical treatments of DN.