[关键词]
[摘要]
目的 利用网络药理学方法研究黄芪治疗糖尿病肾病(DN)的作用机制。方法 以化合物的口服生物利用度(OB)和类药性(DL)为标准,依据中药药理学技术平台(TCMSP)数据库、小分子靶点预测平台(SwissTargetPrediction)、人类基因组注释数据库(Genecards)预测和筛选黄芪的活性成分及治疗DN的作用靶点。采用Metascape数据库对作用靶点的基因本体(GO)注释和京都基因和基因组百科全书(KEGG)通路进行富集分析和蛋白功能归属。结果 从黄芪中筛选得到槲皮素、山柰酚、异鼠李素、芒柄花素、黄芪皂苷I~IV等24个活性成分,作用于172个DN靶点,筛选出表皮生长因子受体、血管内皮生长因子受体、丝裂原活化蛋白激酶、白细胞介素-6、肿瘤坏死因子等18个关键靶点。调节晚期糖基化终末产物及其受体(AGEs-RAGE)介导的信号通路、磷酯酰肌醇3-激酶/蛋白激酶B/叉头框转录因子O(PI3K/Akt/FoxO)信号通路、核转录因子-κB(NF-κB)信号通路、Janus激酶/信号转导子和转录激活因子信号通路等关键代谢通路。参与物质代谢、氧化还原、信号转导、炎症反应等多种生物过程。结论 黄芪及其活性成分通过多个靶点、多条通路发挥治疗DN的作用。
[Key word]
[Abstract]
Objective To study the mechanism of Astragali Radix in the treatment of diabetic nephropathy (DN) by network pharmacology. Methods By using oral bioavailability (OB) and drug like (DL) of compound as reference, according to databases as Traditional Chinese Medicine System Pharmacology (TCMSP) Technology Platform, SwissTarget Prediction, and human genome annotation database (Genecards), the active ingredients of Astragali Radix and the targets of diabetic nephropathy therapy were predicted and screened. Then, the target enrichment analysis of GO functional annotations and KEGG pathways and protein function were analyzed by Metascape. Results A total of 24 active ingredients (such as quercetin, kaempferol, isorhamnetin, formononetin, astragaloside I-IV, etc) were screened from Astragali Radix and acted on 172 diabetes nephropathy targets. Key targets included EGFR, VEGFA, MAPK, IL-6, TNF, etc. Regulation key KEGG signal pathways, such as AGEs-RAGE signal pathway, PI3K/Akt/FoxO signal pathway, NF-kB signal pathway, Jak-STAT signal pathway, etc, participated in many biological processes such as substance metabolism, oxidation-reduction, signal transduction, inflammatory response, etc. Conclusion Astragali Radix and its active ingredients play anti-DN effects through various targets and multiple pathways.
[中图分类号]
R285.5
[基金项目]
山西省回国留学人员科研资助项目(2015-105)