基于网络药理学和分子对接技术探讨黄芩治疗糖尿病心肌病的作用机制

Mechanism of Scutellariae Radix in treatment of diabetic cardiomyopathy based on network pharmacology and molecular docking technique

目的运用网络药理学方法和分子对接技术探讨黄芩抗糖尿病心肌病的活性成分及潜在的作用机制,为后续开展实验研究提供生物信息学基础。方法通过TCMSP数据库及Swiss Target Prediction数据搜集黄芩活性成分与靶点;采用GeneCards、OMIM数据库查找糖尿病心肌病相关靶点;利用Venny 2.1.0获取药物和糖尿病心肌病的交集靶点;借助String平台和Cytoscape 3.9.0软件拓扑分析并筛选出核心成分及靶点;利用DAVID数据库进行黄芩治疗糖尿病心肌病靶点基因本体(GO)分析和基因组百科全书(KEGG)通路富集分析;采用AutoDock 1.5.7和PyMOL 2.4.1软件进行分子对接及可视化作图。结果共筛选出36个黄芩活性成分,与糖尿病心肌病的151个交集靶点。GO富集分析得到775条生物过程,167条分子功能,86条细胞组分;KEGG通路分析得到169条,其中晚期糖基化终末产物及其受体(AGE-RAGE)、磷脂酰肌醇-3-激酶(PI3K)-蛋白激酶B(Akt)、丝裂原活化蛋白激酶(MAPK)、肿瘤坏死因子(TNF)、低氧诱导因子-1(HIF-1)是较关键的通路。分子对接结果显示,汉黄芩素、黄芩素、表小檗碱、黄芩新素等与Akt1、TNF、甘油醛-3-磷酸脱氢酶(GAPDH)、白细胞介素-6(IL-6)蛋白等有较强的相互作用,其中与黄芩素结合性最好。结论黄芩对糖尿病心肌病的治疗作用可能是汉黄芩素、黄芩素、表小檗碱、黄芩新素等活性成分通过调控Akt1、TNF、GAPDH、IL-6等靶点,作用于AGE-RAGE、PI3K-Akt、MAPK等信号通路来实现的。

Objective To explore the active ingredients and potential mechanism of Scutellariae Radix anti-diabetic cardiomyopathy by network pharmacology and molecular docking techniques,and to provide a bioinformatics basis for further experimental studies.Methods The effective components and drug targets of Scutellariae Radix were collected by TCMSP database and SwissTargetPrediction data.GeneCards and OMIM databases were used to identify diabetic cardiomyopathy-related targets.Using Venny 2.1.0 obtain crossover targets of drug and diabetic cardiomyopathy.With String Platform and Cytoscape 3.9.0 Software topology analysis and screening of nucleotide components and targets.DAVID databases was used to analyze the KEGG and GO enrichment pathway of Scutellariae Radix against diabetic cardiomyopathy.Finally,AutoDock1.5.6 and PyMOL2.4.1 software were used for molecular docking and visualization.Results A total of 36 active ingredients of Scutellariae Radix were screened,and 151 crossover targets were identified.GO enrichment analysis yielded 775 biological processes,167 molecular functions and 86 cellular components.KEGG pathway analysis was performed on 169 genes,of which AGE-RAGE,PI3K-Akt,MAPK,TNF,and HIF-1 were the more critical pathways.Molecular docking results showed that wogonin,baicalein,epiberberine,SkullcapflavoneⅡhad strong interaction with Akt1,TNF,GAPDH,IL-6 proteins,among which the binding with baicalein was the best.Conclusion Effect of Scutellariae Radix on diabetic cardiomyopathy may be realized by the regulation of Akt1,TNF,GAPDH1,IL-6 and other core targets by active ingredients such as wogonin,baicalein,epiberberine,and SkullcapflavoneⅡ,acting on AGE-RAGE,PI3K-Akt,MAPK,and other signaling pathways to achieve.