[关键词]
[摘要]
目的 采用网络药理学方法研究人参-黄芪药对治疗2型糖尿病的作用机制。方法 利用中药系统药理学技术平台(TCMSP)获取人参-黄芪药对的主要成分和对应靶点,通过UniProt和DrugBank数据库查询靶点对应的基因,运用Cytoscape3.6.1构建活性成分-靶点相互作用网络。然后通过TTD、DigSee、CTD多个数据库查询2型糖尿病的相关靶点,与人参-黄芪药对作用靶点取交集后获得人参-黄芪药对-T2DM疾病交集靶点。运用STRING在线数据库构建蛋白相互作用(PPI)网络,最后通过DAVID进行GO功能和KEGG通路富集分析。结果 筛选得到41个活性化合物,对应靶点219个,关键靶点涉及PTGS2、PTGS1、ADRB2、NCOA2、SCN5A等。PPI网络包含36个蛋白,包括BCL2、CASP3、CASP8、TGFB1、NOS2、PPARG等。GO功能分析获得269个条目(P<0.05),KEGG通路富集得到71条信号通路(P<0.05),包括胰岛素抵抗通路、PI3K/Akt信号通路、脂肪细胞因子信号通路等。结论 人参-黄芪药对治疗2型糖尿病是多成分、多靶点、多通路协同作用,主要参与炎症反应、细胞凋亡、氧化应激等发挥作用。
[Key word]
[Abstract]
Objective To explore the mechanism of Ginseng Radix et Rhizoma and Astragali Radix drug pair in treatment of type 2 diabetes mellitus using network pharmacology. Methods The active compounds and targets of Ginseng Radix et Rhizoma and Astragali Radix drug pair were obtained by the analysis of traditional Chinese medicine system pharmacology platform (TCMSP), and UniProt and DrugBank databases were used to extract the gene names of the targets. Cytoscape3.6.1 software was used to construct the compound-target network. The disease targets corresponding to T2DM were obtained by using TTD, DigSee, and CTD databases. The Ginseng Radix et Rhizoma and Astragali Radix drug pair-T2DM disease intersection targets were obtained after intersecting with the target of Ginseng Radix et Rhizoma and Astragali Radix drug pair. PPI network was constructed by STRING online database, and gene ontology (GO) analysis of potential genes and pathway enrichment analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) were carried out using DAVID. Results A total of 41 kinds of effective compounds and 219 targets were selected. Key targets included PTGS2, PTGS1, ADRB2, NCOA2, and SCN5A etc. The PPI core network contained 36 protein, and key protein involved in BCL2, CASP3, CASP8, TGFB1, NOS2, and PPARG, etc. The functional analysis of GO obtained 269 GO items (P<0.05), and There were 71 signal pathways (P<0.05) in the KEGG pathway enrichment screening, involving insulin resistance, PI3K-Akt signaling pathway and adipocytokine signaling pathway and so on. Conclusion Ginseng Radix et Rhizoma and Astragali Radix drug pair is a complex process of multi-component, multi-target and multi-pathway in the treatment of type 2 diabetes mellitus, which mainly participate in inflammatory reaction, apoptosis and oxidative stress and so on.
[中图分类号]
R285.5
[基金项目]
国家自然科学基金青年科学基金资助项目(81900468);中华医学会临床药学分会-吴阶平基金会青年基金项目(LCYX-Q025)