基于网络药理学及分子对接方法分析佩兰治疗2型糖尿病作用机制

Analysis on mechanism of Eupatorii herba in the treatment of type 2 diabetes mellitus based on network pharmacology and molecular docking technology

目的运用网络药理学及分子对接方法分析佩兰治疗2型糖尿病(T2DM)的作用机制。方法通过中药系统药理学数据库与分析平台(TCMSP)、Drugbamk、Uni Prot数据库筛选出佩兰的活性成分及靶点;采用GeneCards、CTD及OMIM数据库获取T2DM相关基因,并与药物靶点相互映射,得到共同靶点;采用STRING数据库及Cytoscape 3.6.1软件构建相互作用的网络图并进行拓扑分析,对关键靶点进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析;采用Autodock Tools进行模拟分子对接验证。结果佩兰治疗T2DM的主要化学成分有7个,包括木犀草素、豆甾醇、谷甾醇等;涉及36个潜在核心靶点,包括EGFR、CCND1、VEGFA、CASP3、ERBB2、IL6、AR、MDM2、PPARG、RELA等;GO功能富集分析结果主要涉及基因的转录、核受体活性、激素的受体结合及神经递质等生物学过程;KEGG通路富集分析主要涉及MAPK、PI3K-Akt等信号通路;分子对接结果表明,佩兰的主要活性成分木犀草素、豆甾醇与10个靶标蛋白对接良好。结论佩兰通过多靶点、多通路发挥降糖、抗炎、调节脂质代谢、改善胰岛素抵抗等生物学作用,为临床用药提供了理论依据。

Objective To analyze the mechanism of Eupatorii herba in the treatment of type 2 diabetes mellitus( T2 DM) by applying network pharmacology and molecular docking technology. Methods The active constituents and targets of Eupatorii herba were screened out by Traditional Chinese Medicine Systems Pharmacology( TCMSP) database,Drugbank and Unified Protein( UniProt) database. T2DM related genes were obtained by GeneCards,Comparative Toxicogenomics Database( CTD) and Online Mendelian Inheritance in Man( OMIM) databases,and mapped with drug targets to get common targets.The interaction network map was constructed by Search Tool for the Retrieval of Interacting proteins( STRING) and Cytoscape 3. 6. 1 software and topological analysis was carried out. The key targets were analyzed by gene ontology( GO) functional enrichment analysis and Kyoto gene and genome encyclopedia( KEGG) pathway enrichment analysis,and finally simulated molecular docking was verified by Autodock Tools. Results There are 7 main chemical constituents of Eupatorii herba in the treatment of T2 DM,including luteolin,stigmasterol and sitosterol,etc.;36 potential core targets are involved,including EGFR,CCND1,VEGFA,CASP3,ERBB2,IL6,AR,MDM2,PPARG,RELA,etc. GO function enrichment analysis results mainly involved in gene transcription,nuclear receptor activity,hormone receptor binding,neurotransmitter and other biological processes;KEGG pathway enrichment analysis mainly involved in MAPK,PI3 K-Akt and other signaling pathways;molecular docking results showed that the main active constituents of Eupatorii herba including luteolin,stigmasterol and 10 target proteins docking well.Conclusion Through the multi-targets and multi-pathways,Eupatorii herba has the biological effects of reducing blood sugar,anti-inflammation,regulating lipid metabolism and improving insulin resistance,which provides a theoretical reference for clinical drug use.