基于网络药理学和分子对接法探讨槲皮素治疗2型糖尿病的作用机制

目的 基于网络药理学和分子对接技术探讨槲皮素治疗2型糖尿病（T2DM）的作用机制。方法 通过TCMSP和PharmMapper数据库查询槲皮素的作用靶点,Genecards和CTD数据库收集T2DM的相关靶点,求出槲皮素-T2DM交集靶点并利用STRING和DAVID数据库对交集靶点进行通路分析,使用Cytoscape 3.6.1软件进行"靶点-通路"网络的构建,利用Auto Dock Vina进行分子对接预测槲皮素对T2DM作用靶点的结合能。结果 筛选出槲皮素的潜在靶点312个,与T2DM相关的靶点121个,核心靶点6个：NOS3、CYP1B1、NOS2、TGFB1、TTR和CDKN1A。KEGG信号通路30条,涉及toll样受体信号通路、MAPK信号通路、胰岛素信号通路等。分子对接结果显示,槲皮素与6个核心基因的分子对接亲和力均远小于-20 kJ/mol,结合活性较好。结论 槲皮素治疗T2DM具有多靶点、多通路的作用特点,可能是通过作用于NOS3、CYP1B1、NOS2等核心基因调控toll样受体信号通路、MAPK信号通路、胰岛素信号通路等发挥作用。

Mechanism of quercetin in treatment of type 2 diabetes mellitus based on network pharmacology and molecular docking method

objective To explore the mechanism of quercetin in the treatment of type 2 diabetes mellitus (T2DM) based on network pharmacology and molecular docking technique. Methods Through TCMSP and PharmMapper database query targets of quercetin, Genecards and CTD database to collect the related targets of T2DM, quercetin-T2DM intersection target was obtained and the pathway of intersection target was analyzed by using STRING and DAVID database, using Cytoscape 3.6.1 software "target-pathway" to construct a network diagram, using the Auto Dock Vina molecular docking projections quercetin associativity of T2DM targets. Results 312 potential targets of quercetin were screened out. There were 121 T2DM related targets, six core targets (NOS3, CYP1B1, NOS2, TGFB1, TTR and CDKN1A), 30 KEGG signaling pathways including toll like receptor signaling pathway, MAPK signaling pathway and insulin signaling pathway. The results of molecular docking showed that the affinity of quercetin to the six core genes was far less than -20 kJ/mol, and the binding activity was good. Conclusion Quercetin in the treatment of T2DM has the characteristics of multi-target and multi-pathway. Its possible mechanism of action is through the intervention of NOS3, CYP1B1, NOS2 and other core genes in regulating toll-like receptor signaling pathway, MAPK signaling pathway and insulin signaling pathway.