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

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

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。

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.