基于网络药理学探讨黄连-佩兰药对改善胰岛素抵抗的作用机制

Study on the Mechanism of Huanglian and Peilan in Treating Insulin Resistance Based on Network Pharmacology

目的基于网络药理学探讨黄连-佩兰药对改善胰岛素抵抗的作用机制。方法利用中药系统药理学分析平台(TCMSP)筛选黄连-佩兰药对有效活性成分及其相关靶点。通过OMMI、GeneCards、TTD和DisGeNET数据库获取胰岛素抵抗相关靶点。利用VLOOKUP函数获取二者共同靶点,并应用STRING平台得到核心蛋白相互关系图。运用DAVID 6.8数据库进行GO富集与KEGG通路富集分析,通过Cytoscape 3.8.2软件将结果可视化呈现。运用ZINC数据库及PDB数据库获得蛋白3D结构,利用AutoDock Vina进行分子对接,采用PyMOL将结果可视化处理。结果共获得黄连-佩兰药对有效化学成分16个,药物-疾病共同靶点192个,其中槲皮素、木犀草素等有效活性物质与MAPK1、JUN、AKT1、TP53、APP等靶点相互作用,调控TNF、HIF-1、PI3K-Akt、p53等信号通路。分子对接的结果显示,5个核心靶点与其对应的活性成分表现出良好的亲和力。结论黄连-佩兰药对通过干预炎性反应、脂肪细胞因子、细胞缺氧等作用途径改善脂肪组织、骨骼肌胰岛素抵抗,同时具有改善中枢神经系统胰岛素抵抗的潜在作用。

Objective To explore the mechanism of Huanglian-Peilan in Huazhuo Jiedu Decoction on the effect of on improving insulin resistance based on network pharmacology.Methods TCMSP database was used to screen the effective active ingredients and related targets of Huanglian-Peilan.The target of the IR-related targets was screened by OMMI,GeneCards,TTD and DisGeNET database.Use the VLOOKUP function to get the common target of the two.Use the STRING platform to get the correlation diagram of the core targets.The DAVID 6.8 database was used for GO enrichment and KEGG pathway enrichment analysis,and the results were visualized by Cytoscape 3.8.2 software.Use ZINC database and PDB database to obtain protein 3 D structure,use AutoDock Vina for molecular docking,and visualized by PyMOL.Results 16 effective chemical components of Huanglian-Peilan and 192 common drug-disease targets were obtained.Among them,effective active substances such as quercetin and luteolin interacted with targets such as MAPK1,JUN,AKT1,TP53,and APP.It can regulate TNF,HIF-1,PI3 K-Akt,p53 and other signal pathways.The results of molecular docking showed that the five core targets and their corresponding active ingredients showed good affinity.Conclusion Huanglian-Peilan can improve the insulin resistance of adipose tissue and skeletal muscle by intervening the inflammatory response,adipocytokines,cell hypoxia,and has the potential effect of improving the insulin resistance of the central nervous system.