摘要
基于系统药理学的方法研究金芪降糖片改善胰岛素抵抗的药理机制。从TCMSP数据库查找金芪降糖片的化学成分及靶点,构建中药-活性成分-靶点网络;通过GeneCards数据库获取胰岛素抵抗基因,再与化合物基因取交集,导入STRING数据库制作靶蛋白互作网络(PPI),运用R语言进行GO及KEGG通路富集分析,绘制成“信号通路-靶点-化合物”网络图。共获得54种化合物及222个潜在基因,涉及2538条生物过程,224条分子功能,122条细胞组分及174条通路,确定AKT1、MAPK1、JUN、TP53、APP、RELA、TNF、IL-6、MAPK8、CTNNB1共10个关键基因及槲皮素、山萘酚、木犀草素、小檗碱等关键化合物,主要富集在AGE-RAGE、PI3K-Akt以及流体剪应力及动脉粥样硬化3条糖尿病相关的通路。经通路注释发现其主要调控AGE-RAGE大通路下的PI3K-AKT、MAPK、TGF-β、钙调节等多条子信号通路中,从而调控IL-1、IL-6、IL-8、TNF-α、TF等影响因子的表达,从而改善胰岛素抵抗。该研究揭示了金芪降糖片通过多组分多靶点系统作用,改善胰岛素抵抗防治糖尿病。
This reserch studied on the effective components,potential targets and molecular mechanism of Jinqi Jiangtang tablet for improving insulin resistance based on network pharmacology.Effective components of Jinqi Jiangtang tablet and the targets of these were screened by traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP).In addithion,the related genes of insulin resistance were obtained by searching the human gene database(Gene Cards).The candidate targets of Jinqi Jiangtang tablet in improving insulin resistance were obtained after extracting the intersection network.The“Herbs-active component-target”network was built by virtue of Cytoscape3.7.1 and the Protein-protein Interaction networks were constructed on the STRING platform.The gene ontology(GO)and kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis of candidate genes were performed with R language,and the“pathway-target-active component”network was constructed to further screen key genes and active components.A total of 54 components,222 candidate targets,2538 biological process,224 molecular functions,122 cellular components,174 KEGG pathways and 10 differential expression genes were obtained.The 10 key targets such as AKT1、MAPK1、JUN、TP53、APP、RELA、TNF、IL-6、MAPK8、CTNNB1,and the active components of Jinqi Jiangtang tablet improving insulin resis-tance such as quercetin,kaempferol,luteolin,berberine were screened,and they were found to be enriched in a series of signaling pathways,such as AGE-RAGE signaling pathway in diabetic complications and PI3 K-Akt signaling pathway,fluid shear stress and altherosclerosis,and so on.The pathway annotation of AGE-RAGE signaling pathway in diabetic complications showed that it mainly regulates PI3-Akt,MAPK,TGF-β,calcium regulation and other signaling pathways,thus regulating the expression of IL-1,IL-6,IL-8,TNF-α,TF and other influencing factors,thus improving insulin resistance.Jinqi Jiangtang tablet can regulate insulin resistance and prevent diabetes complications by multi-component,multi-target,and muti-pathway system.These findings provided a theoretical basis for further pharmacological research into the potential mechanism of Jinqi Jiangtang tablet improving insulin resistance.
作者
蒋利荣
覃玥
冯建海
张高荣
卢泳佑
JIANG Li-rong;QIN Yue;FENG Jian-hai;ZHANG Gao-rong;LU Yong-you(School of Chemical and Biological Engineering,Hechi University,Hechi 546300,China;Guangxi Key Laboratory of Microbiology and Plant Resources Development,Hechi 546300,China)
出处
《药物生物技术》
CAS
2022年第4期344-352,共9页
Pharmaceutical Biotechnology
基金
广西自然科学基金项目(No.2020GXNSFAA297218)
广西高校中青年教师基础能力提升项目(No.KY2016LX281,No.2020KY15019,No.2022ky0611)
河池学院高层次人才科研启动费项目(No.XJ2018GKQ014)。
关键词
网络药理学
糖尿病
胰岛素抵抗
金芪降糖片
活性成分
作用机制
Network pharmacology
Diabetes
Insulin resistance
Jinqi Jiangtang tablet
Active component
Mechanism
