基于网络药理学和分子对接研究黄芪治疗糖尿病心肌病的作用机制

Study on the Mechanism of Astragali Radix in the Treatment of Diabetic Cardiomyopathy Based on Network Pharmacology and Molecular Docking

目的:运用网络药理学和分子对接方法研究黄芪治疗糖尿病心肌病(DCM)的作用机制。方法:利用中药系统药理学技术平台数据库(TCMSP)收集黄芪的成分及其相关靶点;通过GeneCards、NCBI、OMIM数据库获取DCM相关疾病靶点。取黄芪成分靶点与DCM疾病靶点的交集基因,作为黄芪对DCM作用的潜在关键靶点基因,将交集基因导入String数据库进行PPI分析,运用Cystoscape 3.8.0构建黄芪活性成分与DCM疾病的共同靶点蛋白互作(PPI)网络,并根据其度值获取核心靶点。使用cytoscape 3.8.0软件构建药物活性成分-疾病靶点网络并筛选发挥治疗作用的主要活性成分,利用String数据和R软件对共同靶点进行GO富集分析及KEGG信号通路富集分析。借助软件Cytoscape 3.8.0,完成网络图“成分-疾病-通路-靶点”的制作。对于筛选所得关键活性成分和DCM治疗的核心靶点开展分子对接验证。结果:共获得黄芪活性成分20个,共同靶点122个。活性成分以槲皮素、异鼠李素、芒柄花素与山奈酚等为主;VEGFA、AKT1、MAPK8、IL6与MAPK1等为关键靶点;KEGG关键通路富集于PI3K-Akt、MAPK及糖尿病(DM)并发症中的AGE-RAGE等信号途径。经由分子对接发现,关键活性成分皆可较强亲和关键靶点。结论:本研究揭示黄芪治疗DCM具有多成分、多靶点、多通路的特点,为黄芪治疗DCM物质基础及作用机制的进一步研究奠定基础。

Objective:To explore the mechanism of Astragali Radix in the treatment of Diabetic Cardiomyopathy through network pharmacology and molecular docking technology. Methods:Collection of constituents and related targets of Astragali Radix was achieved by using TCMSP database of traditional Chinese medicine system pharmacology technology platform;The disease related targets of DCM were obtained through GeneCards、NCBI and OMIM databases. The intersection of Astragali Radix corresponding targets and DCM-related targets were taken as the potential key target gene of Astragali Radix treatment of DCM. The ingredients-targets network and protein interaction network(PPI)was drawn through the String database and Cytoscape 3.8.0 software,and the key targets and components were selected according to their degrees. Gene ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed by utilizing the String database and R software. With the help of the software Cytoscape 3.8.0,the network diagram "component-disease-pathwaytarget" is completed. Molecular docking verification was carried out for the screening of the key active components and the core targets of DCM therapy. Results:A total of 20 active components of Astragali Radix were obtained,and 122 key targets of intersection with DCM were obtained. The main active components are quercetin,isorhamnetin,formononetin and kaempferol.The VEGFA,AKT1,MAPK8,IL6 and MAPK1 are the key targets. The key pathways of KEGG are enriched in PI3K-Akt,MAPK,and AGERAGE in the complications of diabetes mellitus(DM)and so on. Through molecular docking,it was found that all the key active components could have strong affinity with key targets.Conclusion:The effects of Astragali Radix treatment of DCM indicated the multi-component,multi-target,and multi-pathway characteristics of traditional Chinese medicines,providing a scientific basis for further elucidation of the active ingredients and pharmacological action of Astragali Radix.