摘要
目的探讨复方丹参滴丸抗急性高原病(AMS)的可能机制,筛选有效作用成分及相关作用和通路。方法在TCMSP数据库中下载复方丹参滴丸成分及对应靶点信息,在Genecards、OMIM和Drugbank疾病数据库中以“Acute mountain sickness”为关键词搜索下载AMS相关基因,取交集。将共有靶基因输入STRING数据库绘制PPI网络图,用Cytoscape软件构建疾病-成分-靶点网络并使用CytoNCA插件筛选得到关键基因。共有靶基因在DAVID数据库中进行KEGG和GO富集分析。运用分子对接技术进一步验证复方丹参滴丸作用于AMS的核心靶点。结果共筛选得到76个活性成分,43个共同靶点。经拓扑及聚类分析后获得HIF-1α、VEGFα、IL-1β、STAT3、CCL2、CXCL8、TP53、PTGS2共8个关键基因。GO分析显示,复方丹参滴丸抗AMS作用于多个生物过程分子功能,其中相关性较高的有氧化应激代谢过程、凋亡过程、细胞因子受体结合与血红素结合。KEGG富集结果显示复方丹参滴丸抗AMS通过AGE-RAGE.HIF-1 JL-17及VEGF等信号通路发挥作用。分子对接结果显示梆皮素、木樨草素、人参皂昔RH2等活性成分与对应靶分子结合良好。结论复方丹参滴丸抗AMS可能通过影响HIF-1α、VEGFα、IL-1β、STAT3、CCL2、CXCL8、TP53、PTGS2等基因的转录,以及氧化应激、炎症、调节细胞分凋亡、炎性细胞因子的表达及缺氧等通路发挥治疗作用。
Objective To explore the possible mechanism by which compound Danshen dropping pills combat acute mountain sickness(AMS),and screen effective components,related functions and pathways.Methods The data on components and corresponding targets of compound Danshen dropping pills was downloaded from the TCMSP database,while information on AMS related genes was retrieved from Genecards,OMIM and Drugbank databases with"acute mountain sickness"as the keywords.The common target genes were entered into the String database to draw the PPI network,the"disease-component-target"network was constructed with Cytoscape software,and the hub genes were screened by CytoNCA.GO function and KEGG pathways on the common targets of compound Danshen dropping pills were enriched in the DAVID database.Molecular docking technology was used to further verify the interactions between the common targets and corresponding compounds.Results A total of 76 active components and 43 common targets were screened.Hub genes,including HIF-lα、VEGFα、IL-1β、STAT3,CCL2,CXCL8,TP53 and PTGS2,were found to be related to the effects of Danshen dropping pills after topology and cluster analysis.Go analysis showed that these pills had anti-AMS effects via multiple biological processes and molecular functions.Among them,the metabolic process of oxidative stress,apoptosis process,cytokine receptor binding and heme binding were significantly correlated.KEGG enrichment results showed that these pills were effective for AMS through AGE-RAGE,HIF-1,IL-17 and VEGF signaling pathways.Conclusion Compound Danshen dropping pills may help ameliorate AMS by regulating the transcription of HIF-1α,VEGFα,IL-1β,STAT3,CCL2,CXCL8,TP53 and PTGS2.
作者
闫佳怡
阮盼盼
高月
YAN Jia-yi;RUAN Pan-pan;GAO Yue(School of Pharmacy,Guangdong Pharmaceutical University,Guangzhou 511400,China;Institute of Radiation Medicine,Academy of Military Medical Sciences,Academy of Military Sciences,Beijing 100850,China;School of Life Sciences,Hebei University,Baoding 071002,China)
出处
《解放军药学学报》
CAS
2022年第2期95-99,105,共6页
Pharmaceutical Journal of Chinese People's Liberation Army
基金
国家重点研发计划,No.2019YFC1604900。
关键词
网络药理
复方丹参滴丸
急性高原病
HIF-1通路
network pharmacology
compound Danshen dropping pills
acute mountain sickness
HIF-1 signaling pathway
