天然产物研究与开发 ›› 2021, Vol. 33 ›› Issue (2): 304-312.doi: 10.16333/j.1001-6880.2021.2.015

• 数据研究 • 上一篇    下一篇

基于网络药理学探讨“黄芪-白术-熟地黄”组方防治肾病综合征的作用机制

轩晨1,席雨蒙2,张玉笛2,陶春鹤2,章蓝月2,曹文富1,2*   

  1. 1重庆医科大学附属第一医院中西医结合科;2重庆医科大学中医药学院,重庆 400016
  • 出版日期:2021-02-28 发布日期:2021-03-04
  • 基金资助:
    国家自然科学基金(81573860)

Study on the mechanism of Huangqi-Baizhu-Shudihuang formula in the treatment of nephrotic syndrome based on network pharmacology

XUAN Chen1,XI Yu-meng2,ZHANG Yu-di2,TAO Chun-he2,ZHANG Lan-yue2,CAO Wen-fu1,2 *   

  1. 1Department of Integrated Traditional Chinese Medicine and Western Medicine,the First Affiliated Hospital of Chongqing Medical University;2College of Traditional Chinese Medicine,Chongqing Medical University,Chongqing 400016,China
  • Online:2021-02-28 Published:2021-03-04

摘要:

本研究旨在通过网络药理学方法和分子对接技术探讨黄芪-白术-熟地黄组方(HBS)治疗肾病综合征的作用机制。通过多个数据库获取肾病综合征基因并进行功能模块分解,找出肾病综合征基因参与的主要生物学过程。通过文献以及数据库查找HBS活性成分和基因靶点,筛选出HBS治疗肾病综合征的有效靶点。通过有效靶点的KEGG和GO富集分析,找出其参与的主要生物学过程和信号通路,并以此构建靶点-生物功能(TF)网络和靶点-信号通路(TP)网络,综合分析后得到HBS治疗肾病综合征的机制网络,最后使用分子对接技术将HBS化合物和关键靶蛋白进行对接验证。肾病综合征基因主要与细胞增殖、凋亡以及肾脏发育有关。共筛选出18个有效靶点,有效靶点主要与免疫反应、炎症反应、细胞增殖和凋亡的调节有关,主要富集在IL-17、NF-κB、PI3K/Akt、FoxO、p53和Jak/STAT等信号通路上,这些信号通路是HBS调节免疫反应、炎症反应、细胞增殖和凋亡的主要途径。此外,分子对接结果证实HBS化合物与TGFβ1、PTGS2、IL1B、IL2、IL4、IL10、TNF和CD40LG等炎性细胞因子具有较好的结合活性。本研究表明HBS调控IL-17、NF-κB、PI3K/Akt、FoxO、p53和Jak/STAT信号通路上关键蛋白的表达,可能通过调节免疫反应和炎症反应,改善系膜细胞和足细胞的增殖、凋亡水平,进而对包括蛋白尿和肾小球硬化在内的肾病综合征病理改变发挥治疗作用。

关键词: 黄芪-白术-熟地黄组方, 肾病综合征, 网络药理学, 作用机制

Abstract:

To explore the mechanism of Huangqi-Baizhu-Shudihuang formula (HBS) in the treatment of nephrotic syndrome by network pharmacology and molecular docking technology.Nephrotic syndrome genes were obtained from multiple databases and decomposed into functional modules to find out the main biological processes of nephrotic syndrome.The active components and targets of HBS were searched through literatures and databases,and the effective targets for the treatment of nephrotic syndrome were screened out.Through the KEGG and GO enrichment analysis of effective targets,the main biological processes and signal pathways were found out,and the target-function (TF) and target-pathway (TP) networks were constructed based on the analysis.After comprehensive analysis,the possible mechanism of HBS treatment for nephrotic syndrome was obtained.Finally,molecular docking technology was used to verify the docking of HBS compounds and key target proteins.Nephrotic syndrome genes are mainly related to cell proliferation,apoptosis and kidney development.A total of 18 effective targets were screened out.The effective targets are mainly related to the regulation of immune response,inflammatory response,cell proliferation and apoptosis,which are mainly concentrated in the signal pathways of IL-17,NF-κB,PI3K/Akt,FOXO,p53 and JAK/STAT.These are the possible pathways for HBS to regulate immune response,inflammatory response,cell proliferation and apoptosis.In addition,molecular docking results confirmed that HBS compounds had good binding activity with inflammatory cytokines such as TGFβ1,PTGS2,IL1B,IL2,IL4,IL10,TNF and CD40LG.This study suggests that HBS regulates the expression of key proteins in IL-17,NF-κB,PI3K/Akt,FOXO,p53 and JAK/STAT signaling pathways,which may improve the proliferation and apoptosis of mesangial cells and podocytes by regulating immune response and inflammatory response,thus playing a therapeutic role in the pathological changes of nephrotic syndrome including proteinuria and glomerulosclerosis.

Key words: Huangqi-Baizhu-Shudihuang formula, nephrotic syndrome, network pharmacology, mechanism

中图分类号:  R259