天然产物研究与开发 ›› 2021, Vol. 33 ›› Issue (8): 1382-1390.doi: 10.16333/j.1001-6880.2021.8.014

• 数据研究 • 上一篇    下一篇

基于网络药理学的丹参-川芎药对治疗阿尔茨海默病的作用机制分析

杨梦琳1,2,3,周小青2,3*,伍大华2,4,张运辉1,2,3,郑彩杏2,3,童天昊2,3   

  1. 1重庆三峡医药高等专科学校中医学院,重庆 404120;2湖南中医药大学;3 2011数字中医药协同创新,长沙 410208;4湖南省中医药研究院附属医院,长沙 410006

  • 出版日期:2021-08-28 发布日期:2021-08-30
  • 基金资助:
    国家自然科学基金(81373702);国家自然科学基金(81874462);重庆市中医药重点学科(中医基础理论)建设项目(渝中医[2021]16号)

Mechanism research of Danshen-Chuanxiong in treating Alzheimer's disease based on network pharmacology

YANG Meng-lin 1,2,3,ZHOU Xiao-qing2,3*,WU Da-hua2,4,ZHANG Yun-hui1,2,3,ZHENG Cai-xing2,3,TONG Tian-hao2,3#br#

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  1. 1Chongqing Three Gorges Medical College of Chinese Medicine,Chongqing 404120,China;2Hunan University of Chinese Medicine; 3 2011 Digtal Traditional Chinese Medicine Collaborative Innovation,Changsha 410208,China; 4Affiliated Hospital of Hunan Provincial Academy of Traditional Chinese Medicine,Changsha 410006,China

  • Online:2021-08-28 Published:2021-08-30

摘要:

利用网络药理学方法研究丹参-川芎药对治疗阿尔茨海默病(AD)的作用机制。经数据库查找及文献检索,获得丹参和川芎的有效成分,利用STITCH与TCMSP数据库得到有效成分作用靶点,并构建药物-靶标网络、PPI网络,利用Metascape数据库对丹参-川芎作用靶点进行GO分析以及KEGG代谢通路富集分析。最后利用MTT实验、ELISA法、流式细胞仪和荧光定量PCR实验验证丹参-川芎对PC12细胞的保护作用。结果显示筛选出丹参-川芎药对25个活性成分和作用于AD的靶点105个,GO分析相关度前20个靶点分子功能,前10条重要信号通路。细胞实验证实了丹参-川芎可显著提高PC12细胞的细胞存活率和拮抗PC12细胞的炎症反应及降低PC12细胞的凋亡率,并抑制p38MAPK/NF-κB信号通路的激活。丹参-川芎药对具有多种有效成分以协同的方式与多个靶点、多种途径相互作用,主要通过抗细胞凋亡、抑制炎症反应等对AD发挥主要的治疗作用,为其临床应用提供了理论依据。

关键词: 丹参, 川芎, 阿尔茨海默病, 网络药理学, 信号通路

Abstract:

To study the mechanism of Danshen-Chuanxiong(DS-CX) in the treatment of Alzheimer's disease(AD) by using network pharmacology.Through database search and literature retrieval,the effective ingredients of DS and CX were obtained,and the targets of active ingredients were obtained through STITCH and TCMSP databases.And the drugs-targets network and PPI network were built.Then,gene ontology (GO) analysis and KEGG metabolic pathway enrichment analysis were performed on the action targets of DS-CX were performed using Metascape database.Finally,MTT,ELISA,flow cytometer and fluorescence quantitative PCR experiment were carried out to verified the protective effect of DS-CX on PC12 cells.The results showd that 25 active components of DS-CX were screened and 105 targets for the treatment of Alzheimer's disease,top 20 target molecular functions by GO analysis,and top 10 important signaling pathways.Cell experiments also proved that DS-CX significantly increased the cell survival rate of PC12 cells and antagonize the inflammatory response of PC12 cells and reduce the apoptosis rate of PC12 cells,and inhibited the activation of p38MAPK/NF-κB signaling pathway.DS-CX couplet medicines had a variety of active ingredients that interact with multiple targets and multiple pathways in a synergistic manner to play a major therapeutic role on AD by anti-apoptosis and anti-inflammatory,which provides the theoretical basis for its clinical application.

Key words: Danshen, Chuanxiong, Alzheimer’s disease, pharmacology, signaling pathway

中图分类号:  R285.5