天然产物研究与开发 ›› 2024, Vol. 36 ›› Issue (3): 520-527.doi: 10.16333/j.1001-6880.2024.3.015

• 数据研究 • 上一篇    下一篇

基于网络药理学、分子对接技术及实验验证研究黄芪提取物治疗缺血缺氧性脑病的机制

宋丽娅*,李丽华,毕思童   

  1. 首都医科大学附属北京潞河医院儿科,北京 101149
  • 出版日期:2024-03-20 发布日期:2024-03-20
  • 基金资助:
    首都医科大学2019年度科技技术、社科计划(KM201910025001)

Study on the mechanism of Astragali Radix extract in treating hypoxic-ischemic encephalopathy based on network pharmacology,molecular docking and experimental validation 

SONG Li-ya*,LI Li-hua,BI Si-tong   

  1. Department of Pediatrics,Luhe Hospital,Capital Medical University,Beijing 101149,China
  • Online:2024-03-20 Published:2024-03-20

摘要:

运用网络药理学、分子对接技术探究黄芪提取物治疗缺血缺氧性脑病(hypoxic-ischemic encephalopathy,HIE)的机制,并进行实验验证。通过中药系统药理学数据库平台(TCMSP)、UniProt、GeneCards和OMIN数据库获得黄芪提取物的主要活性成分和基因靶点,通过GeneCards数据库获得HIE的相关靶点;利用Cytoscape软件构建黄芪提取物“活性成分-药物靶点”网络。应用PDB和TCMSP数据库获取分子结构,使用SYBYL-X2.1软件进行模拟分子对接。建立大鼠动物试验模型,采用Western blot法检测关键蛋白的表达情况。根据TCMSP数据库,共得到黄芪提取物的70个活性成分及其350个相关靶点,去除重复靶点和基因注释后,最终获得“黄芪提取物”有效成分的120个靶点。通过将黄芪提取物的120个靶点与HIE的前242个靶点(相关性分数>5)相映射,筛选出黄芪提取物治疗HIE的18个潜在靶点,发现4-羟基肉桂酸、顺式阿维酸、黄芪紫檀烷苷、常春藤皂苷元、华良姜素为关键活性成分。将18个潜在靶点输入STRING中进行蛋白相互作用分析,共发现3个核心靶点(degree值>30),分别为诱导型一氧化氮合酶2(nitric oxide synthase 2,NOS2)、前列腺素氧化环化酶2(prostaglandin-endoperoxide synthase 2,PTGS2)、超氧化物歧化酶1(superoxide dismutase 1,SOD1)。动物实验显示,黄芪提取物能够降低大鼠模型海马组织内的NOS2、PTGS2、MAPK4、CASP8蛋白表达。通过网络药理学分析和实验验证得出黄芪提取物能够通过多靶点、多通路起到抑制神经元凋亡、保护神经细胞的作用。

关键词: 黄芪提取物, 缺血缺氧性脑病, 分子对接, 网络药理学

Abstract:

Network pharmacology and molecular docking techniques were used to explore the mechanism of Astragali Radix extract in the treatment of hypoxic-ischemic encephalopathy (HIE).ischemic encephalopathy (HIE) was studied and verified.The main active components and gene targets of Astragali Radix extract were obtained through TCMSP,UniProt,GeneCards and OMIN databases,and HIE related targets were obtained through GeneCards database.The "active ingredient-drug target" network of Astragali Radix extract was constructed using Cytoscape software.PDB and TCMSP databases were used to obtain the molecular structure,and SYBYL-X2.1 software was used to simulate the molecular docking.The rat model was established and the expression of key proteins was detected by Western blot.According to the TCMSP database,a total of 70 active components and 350 related targets of Astragali Radix extract were obtained.After removing repeated targets and gene annotation,120 targets of active components of Astragali Radix extract were obtained.By mapping 120 targets of Astragali Radix extract with the first 242 targets of HIE (correlation score >5),18 potential targets of Astragali Radix extract for HIE were selected.4-Hydroxycinnamic acid,cis-ferulic acid,astrapterocarpan,hederagenin and kumatakenin were found to be the key active ingredients.Eighteen potential targets were input into STRING for protein interaction analysis,and a total of three core targets (degree>30) were found,which were respectively inducible nitric oxide synthase 2(NOS2),prostaglandin-endoperoxide synthase 2 (PTGS2),superoxide dismutase 1 (SOD1).Animal experiments showed that Astragali Radix extract could reduce the expression of NOS2,PTGS2,MAPK4 and CASP8 proteins in the hippocampus of rat models.Through network pharmacological analysis and experimental verification,it is concluded that Astragali Radix extract can inhibit neuronal apoptosis and protect nerve cells through multi-target and multi-pathway.

Key words: Astragali Radix extract, ischemic hypoxic encephalopathy, molecular docking, network pharmacology

中图分类号:  R286