金芪降糖片入血成分抗糖尿病机制的网络药理学研究

目的基于网络药理学方法研究金芪降糖片入血成分治疗糖尿病的作用机制。方法通过文献挖掘确定金芪降糖片入血成分,在TCMSP、Swiss Target Prediction数据库检索入血成分靶点,通过GeneCards数据库查询糖尿病靶点,将糖尿病靶点与入血成分靶点筛重得到入血成分抗糖尿病靶点,借助Cytoscape软件构建入血成分-抗糖尿病靶点网络;应用STRING平台构建入血成分抗糖尿病靶蛋白相互作用网络,并导入Cytoscape软件计算拓扑参数,筛选关键靶点;通过Cytoscape中"ClueGO"插件进行GO生物过程分析;利用DAVID数据库进行KEGG通路富集分析。结果金芪降糖片16个入血成分作用于123个糖尿病靶点,22个关键靶点包括炎症因子IL1β、IL6、IL8、TNF、PTGS2;氧化还原反应酶CAT、SOD1、MAOB;心血管靶点TBXA2R、VEGFA、NOS3;细胞周期与凋亡蛋白CDK2、MAPT、CASP3等。参与急性炎症反应调节、外源性凋亡信号通路负调节、单加氧酶活性调节、过氧化氢生物合成等14大类生物过程。调节胰岛素抵抗、I型糖尿病、TNF信号通路、NF-κB信号通路、MAPK信号通路、PI3K-Akt信号通路等。结论金芪降糖片主要通过抗炎、抗氧化、调节细胞凋亡及糖代谢等药理作用,减轻胰岛β细胞损伤,改善胰岛素抵抗,产生抗糖尿病作用。

Mechanism of Constituents Migrating to Blood of Jinqi Jiangtang Tablet in Treating Diabetes Mellitus by Network Pharmacology

OBJECTIVE To investigate the mechanism of constituents migrating to blood of Jinqi Jiangtang tablet in treating diabetes mellitus based on network pharmacology. METHODS Searched literature to obtain constituents migrating to blood of Jinqi Jiangtang tablet, screened targets corresponding to the constituents migrating to blood in TCMSP and Swiss Target Prediction databases, and found the targets of diabetes from GeneCards database, anti-diabetic targets of constituents migrating to blood were obained by their intersection. The results were imported into Cytoscape software to construct a network of constituents migrating to blood anti-diabetic targets. Used STRING platform to construct a PPI network, imported the network to Cytoscape software to calculate topological parameters, and picked out key targets;the gene ontology(GO) function enrichment analysis was performed by "ClueGO" plug-in;the DAVID database was used for KEGG pathway enrichment analysis. RESULTS Sixteen constituents migrating to blood of Jinqi Jiangtang tablet acted on 123 diabetic targets. Twenty two key targets included inflammatory factors: IL1β, IL6, IL8, TNF, and PTGS2;redox reaction enzymes: CAT, SOD1, MAOB;cardiovascular targets point: TBXA2 R, VEGFA, NOS3;cell cycle and apoptosis proteins: CDK2, MAPT, CASP3, et al. They involved in 14 major biological processes such as regulation of acute inflammatory response, negative regulation of extrinsic apoptotic signaling pathway, regulation of monooxygenase activity, and hydrogen peroxide biosynthetic processe, and regulated multiple signaling pathways such as insulin resistance, type I diabetes mellitus, TNF signaling pathway, NF-κB signaling pathway, MAPK signaling pathway, PI3 K-Akt signaling pathway. CONCLUSION Jinqi Jiangtang tablet mainly has pharmacological effects such as anti-inflammatory, anti-oxidation, regulation of apoptosis and glucose metabolism, alleviates islet β-cell damage, reduces insulin resistance, finally produces anti-diabetic effect.