Abstract
Objective:To explore the possible pharmacodynamic material basis and mechanisms of Xiaoshuan Granules(XS)in the treatment of cerebral ischemia.Methods:Ultra-high performance liquid chromatography-high-resolution tandem mass spectrometry(UPLC-HRMS/MS)was used to qualitatively analyze XS and the drug-containing plasma of rats after oral administration of XS.The targets of these components were predicted by the PubChem database,the SwissTargetPrediction database,and the Super-PRED database,while cerebral ischemia-related targets were screened by the GeneCards database,the DisGeNET database,and the OMIM database.The common targets were obtained by the Venny platform.Protein-Protein Interaction(PPI)networks were constructed by STRING database.The core components and core targets were screened by Cytoscape software.The common targets were analyzed by Gene Ontology(GO)function and KEGG pathway enrichment with the David database.The molecular docking between the core components and core targets was verified using Autodock software.Results:A total of 64 components in XS were identified,while 11 components in the drug-containing plasma of rats after oral administration of XS were identified.A total of 177 common targets were found between the components in drug-containing plasma and cerebral ischemia,among which cycloastragenol,ferulic acid,isomucronulatol and levistilide A were core components,while signal transducer and activator of transcription 3(STAT3),Akt serine/threonine kinase 1(Akt1),tyrosine-protein kinase Src(SRC),epidermal growth factor receptor(EGFR),nuclear factor kappa-B 1(NFKB1),hypoxia-inducible factor 1α(HIF1A),estrogen receptor α(ESR1),heat shock protein 90α family class A member 1(HSP90AA1)and tumor necrosis factor(TNF)were core targets.GO function and KEGG pathway enrichment analysis showed that these common targets were mainly involved in multiple biological processes,such as response to hypoxia,positive regulation of phosphatidylinositol 3-kinase/protein kinase B signaling,inflammatory response,positive regulation of angiogenesis,negative regulation of apoptotic process,and multiple signaling pathways.They regulated vascular endothelial growth factor(VEGF),hypoxia-inducible factor-1(HIF-1),interleukin-17(IL-17),apoptosis,TNF,neurotrophin,and other signaling pathways.Molecular docking showed that cycloastragenol,ferulic acid,isomucronulatol and levistilide A had better binding activity with these core targets.Conclusion:Cycloastragenol,ferulic acid,isomucronulatol,and levistilide A are the important active components of XS,which have a protective effect against cerebral ischemia by regulating VEGF,HIF-1,IL-17,apoptosis,TNF,neurotrophin and multiple signaling pathways,reducing neuronal apoptosis,inhibiting inflammatory response,and promoting neurogenesis and angiogenesis.关键词
缺血性脑卒中/消栓颗粒/超高效液相色谱-高分辨串联质谱法/网络药理学/分子对接Key words
cerebral ischemia/Xiaoshuan Granules/ultra-high performance liquid chromatography-high resolution tandem mass spectrometry/network pharmacology/molecular docking分类
医药卫生
