黄芪-当归治疗糖尿病肾病作用机制的网络药理学研究

Mechanism of Astragali Radix-Angelcia Sinensis Radix in Treatment of Diabetic Nephropathy Based on Network Pharmacology

目的基于网络药理学方法探讨黄芪-当归治疗糖尿病肾病的物质基础和作用机制。方法利用中药系统药理学分析平台(TCMSP),以口服生物利用度(OB)≥30%、类药性(DL)≥0.05为筛选条件,结合文献调研得到黄芪-当归候选化合物,并通过该数据库检索与候选化合物相关的作用靶点。通过TCMSP与比较毒物基因组学数据库(CTD)获得糖尿病肾病相关基因。通过在线韦恩图分析得到候选化合物与糖尿病肾病的交集基因。通过STRING 10.0数据库构建出交集蛋白相互作用网络。通过DAVID数据库对交集蛋白进行基因本体(GO)分析和基于京都基因与基因百科全书(KEGG)对信号通路富集分析。利用Cytoscape 3.6.1软件构建黄芪-当归治疗糖尿病肾病的成分-靶点-信号通路网络。结果所构建的黄芪-当归治疗糖尿病肾病的成分-靶点-信号通路网络涉及槲皮素、山奈酚、芒柄花黄素、毛蕊异黄酮、异鼠李素、咖啡酸酯等10个活性成分;涉及CCL2、IL-1β、IL-1α、VEGFA等12个潜在靶点;涉及糖尿病信号通路、肿瘤坏死因子信号通路、丝裂原活化蛋白激酶信号通路及Nod样受体信号通路等31条信号通路。结论黄芪-当归药对可能通过槲皮素、异鼠李素等多种成分作用于CCL2、IL-1β等靶点,调控糖尿病、Nod样受体等多条信号通路,进而发挥治疗糖尿病肾病的作用。

Objective The mechanism and the material basis of Astragali radix-Angelicae sinensis radix in the treatment of diabetic nephropathy were investigated based on network pharmacological method. Methods The chemical components and the targets related to Astragali radix-Angelicae sinensis radix were searched on the traditional Chinese medicine system pharmacology platform(TCMSP),the oral bioavailability(OB)≥ 30% and drug likeness(DL) ≥ 0.05 were used as the screening criteria for molecular compounds. Genes related to diabetic nephropathy were screened by TCMSP and comparative Toxicogenomics Database(CTD). Common genes of candidate compounds and diabetic nephropathy were obtained through online Wayne diagrams. Intersection protein interaction network was constructed by STRING 10.0. Gene Ontology(GO)analysis and enrichment analysis based on the Kyoto Encyclopedia of Genes and Genes(KEGG)of intersection proteins were carried out via DAVID database. Cytoscape3.6.1 software was used to construct a components-targets-pathway network of Astragali radix-Angelicae sinensis radix for treating diabetic nephropathy. Results The compounds-targets-pathway network of Astragali radixAngelicae sinensis radix related to diabetic nephropathy contained 10 compounds,included quercetin,kaempferol,formononetin,calycosin,isorhamnetin,caffeate,acted on 12 potential targets including CCL2,IL-1β,IL-1α,tumor necrosis factor,which had effects on type I diabetes mellitus,NOD-like receptor signaling pathway,MAPK signaling pathway,and VEGF signaling pathway. Conclusion The active components of Astragali radix-Angelicae sinensis radix such as quercetin,isorhamnetin may act on CCL2,IL-1β and other targets,and regulate diabetes and Nod-like receptors signaling pathways,thereby exert its role in treating diabetic nephropathy.