摘要
目的通过网络药理学和蛋白质组学分析开心散干预卒中后认知障碍(PSCI)的作用机制。方法利用TCMSP、ETCM数据库、TCMID数据库和BATMAN数据库,检索开心散组方药物活性成分及作用靶点。采用高效液相色谱法串联质谱(HPLC-MS/MS)法测定PSCI患者血液样本差异基因;通过STRING数据库构建PPI网络,采用Cytoscape 3.9.1软件构建“活性成分-靶点-疾病”网络,通过DAVID数据库进行GO功能和KEGG通路富集分析,并利用AutoDockTools 1.5.7对活性成分和靶点进行分子对接验证。结果获得开心散2292个药物靶点,PSCI患者临床样本共鉴定出248个差异基因,其中125个上调,123个下调。KEGG通路主要富集于TNF信号通路、PI3K-Akt信号通路、HIF-1信号通路、MAPK信号通路等。分子对接结果表明,开心散活性成分山柰酚、核黄素、麝香草酚与CXCR4、APOE、AGT、SLC2A1靶点存在较强的结合作用。结论开心散山柰酚、核黄素、麝香草酚等活性成分可能通过调控CXCR4、APOE、AGT、SLC2A1等靶点,激活或抑制TNF信号通路、PI3K-Akt信号通路、HIF-1信号通路、MAPK信号通路,从而治疗PSCI。
Objective To analyze the mechanism of Kaixin Powder in intervening post-stroke cognitive impairment(PSCI)through network pharmacology and proteomics analysis.Methods TCMSP,ETCM,TCMID,and BATMAN databases were used to retrieved the active components and gene targets of Kaixin Powder.Differential genes in PSCI patients'blood samples were determined using high-performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS).A protein-protein interaction network(PPI)was constructed using the STRING database,and a drug-PSCI-gene network was built with Cytoscape software.GO and KEGG enrichment analysis of targets were performed using the DAVID database,and the effective components were docked with targets using AutoDock software for molecular docking verification.Results A total of 2292 drug targets within Kaixin Powder were identified,with 248 differential genes found in clinical samples from PSCI patients,including 125 up-regulated and 123 down-regulated genes.KEGG enrichment analysis identified pathways including the TNF signaling pathway,PI3K-Akt signaling pathway,HIF-1 signaling pathway,and MAPK signaling pathway.The molecular docking results indicated that the three active components of Kaixin Powder,β-sitosterol,riboflavin,and musk ketone,had strong binding effects with four target proteins CXCR4,APOE,AGT,and SLC2A1.Conclusion The active components of Kaixin Powder,such asβ-sitosterol,riboflavin,and musk ketone,may treat PSCI by modulating the targets such as CXCR4,APOE,AGT,and SLC2A1,thereby activating or inhibiting pathways such as TNF signaling pathway,PI3K-Akt signaling pathway,HIF-1 signaling pathway,and MAPK signaling pathway.
作者
齐宝云
高飞娟
于久旺
刘飞
Qi Baoyun;Gao Feijuan;Yu Jiuwang;Liu Fei(Department of Neurology,Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine,Beijing 100700,China;Department of Traditional Chinese Neurology,Mongolian Traditional Chinese Medicine Hospital,Hohhot 010020,China)
出处
《国际中医中药杂志》
2024年第9期1171-1177,共7页
International Journal of Traditional Chinese Medicine
基金
北京中医药大学青年教师项目(2019-BUCMXJKY021)。
关键词
认知障碍
卒中
网络药理学
蛋白质组学
开心散
Cognition disorders
Stroke
Network pharmacology
Proteomics
Kaixin Powder
