基于网络药理学及分子对接的黄芪散治疗2型糖尿病机制探讨

Mechanism of Huangqi San in the Treatment of Type 2 Diabetes Mellitus Based on Network Pharmacology and Molecular Docking

【目的】运用网络药理学及分子对接探讨黄芪散治疗2型糖尿病(T2DM)的作用机制。【方法】通过中药系统药理学分析平台(TCMSP)查找黄芪散组方中黄芪、葛根、桑白皮的活性成分和作用靶点,通过GeneCards和OMIM数据库查询与T2DM相关的疾病靶点,通过UniProt数据库查询成分和疾病靶点对应的基因名,利用Cytoscape 3.6.1软件构建黄芪散活性成分-靶点网络、蛋白相互作用(PPI)网络,并通过Merge功能构建疾病-成分-靶点网络,筛选出黄芪散治疗T2DM的核心靶点,最后通过DAVID数据库对核心靶点蛋白进行基因本体论(GO)生物过程分析及京都基因与基因组百科全书(KEGG)通路富集分析,预测其作用机制,并绘制GO和KEGG气泡图进行数据可视化。【结果】研究得到包括槲皮素、山柰酚、刺芒柄花素等在内的38个活性成分和ESR1、JUN、PTGS2、AKT1和MAPK1等75个关键靶点。GO功能富集分析得到113个GO条目(P<0.05),主要包括蛋白酪氨酸激酶活性、生长因子活性和核受体活性等生物过程,KEGG富集得到157条信号通路(P<0.05),主要涉及晚期糖基化终末产物(AGEs)-晚期糖基化终末产物受体(RAGE)信号通路、肿瘤坏死因子(TNF)信号通路、磷脂酰肌醇3-激酶(PI3K)/Akt信号通路等。【结论】黄芪散治疗T2DM可能的机制是通过抑制炎症因子分泌,参与抗炎反应,降低氧化应激,激活PI3K/Akt通路等来改善胰岛素抵抗,提高胰岛素敏感性,降低血糖。

Objective To explore the mechanism of Huangqi San in treating type 2 diabetes mellitus(T2DM)based on network pharmacology and molecular docking.Methods The active components and action targets of Radix Astragali seu Hedysari,Radix Puerariae and Cortex Mori in Huangqi San were searched through Traditional Chinese Medicine Systems Pharmacology(TCMSP);the disease targets associated to T2DM were searched through GeneCards and OMIM databases,and the gene names corresponding to the components and disease targets were searched through UniProt database.The active component-target network and protein interaction(PPI)network of Huangqi San were constructed by Cytoscape 3.6.1 software,and the disease-component-target network was constructed by merge function to screen the core targets of Huangqi San for T2DM treatment.Finally,gene ontology(GO)process analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed on the core target protein through DAVID database to predict its mechanism of action,and GO and KEGG bubble chart were drawn for data visualization.Results A total of 38 active components including quercetin,kaempferol and formononetin,etc.,and 75 key targets including ESR1,JUN,PTGS2,AKT1 and MAPK1 etc.were obtained.GO functional enrichment analysis obtained 113 GO items(P<0.05),mainly including protein tyrosine kinase activity,growth factor activity and nuclear receptor activity and other biological processes;KEGG enrichment obtained 157 signaling pathways(P<0.05),which mainly involves advanced glycation end products(AGEs)-their receptor(RAGE)signaling pathway,tumor necrosis factor(TNF)signaling pathway,phosphatidylinositol 3-kinase(PI3K)-Akt signaling pathway.Conclusion The possible mechanism of Huangqi San in the treatment of T2DM is to improve insulin resistance and insulin sensitivity,reduce blood glucose by inhibiting the secretion of inflammatory factors,participating in anti-inflammatory responses,reducing oxidative stress,and activating PI3K/Akt pathway.