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Revealing the material basis of MMP9-mediated activating blood and removing blood stasis drugs on Danshen-Ligusticum chuanxiong anti- vascular effect

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摘要 Objective:Reveal the material basis and mechanism of angiogenesis effect of Danshen-chuanxiong herb-partners.Methods:The effective components of Danshen and chuanxiong were searched in the TCM System Pharmacology Database(TCMSP),and the drug targets were searched in the Swiss Target Prediction database;in the Disease-Gene Database(DisGeNET))Search for angiogenesis-promoting and inhibiting angiogenesis targets;use the protein interaction database(STRING)database and Cytoscape software to analyze the network core targets;use the DAVID database to enrich the drug-disease target intersection for GO and KEGG;RT-qPCR experiments verified the effect of luteolin on MMP9 gene expression;in vitro tube formation experiments analyzed the effect of luteolin on endothelial cell neovascularization.Results:After analysis,it is concluded that Danshen has 10 active ingredients and 50 angiogenesis targets;Chuanxiong has 2 active ingredients and 4 angiogenesis targets.The intersection of drug-taking targets yielded 9 targets,including AR,PARP1,MMP9,MMP2,MMP12,AKR1B10,ABCC1,CDK6,and STAT3.After analyzing the active ingredient-target network graph of Danshen/Chuanxiong,it was concluded that luteolin is the key chemical ingredient.After protein interaction(PPI)analysis,the results showed that MMP9 is the core target.The KEGG pathway is mainly enriched in 5 signaling pathways,the most important pathway is cancer-related pathways.There are 22 main biological processes of GO,which mainly involve collagen catabolism,protein extracellular matrix,metal endopeptidase activity,etc.The preliminary analysis of tubule formation experiment shows that luteolin inhibits angiogenesis and down-regulates the expression of MMP9 gene.Conclusion:Luteolin,the key chemical component of the Danshen-Ligusticum chuanxiong drug pair,inhibits angiogenesis by regulating the MMP9 target,and develops the reverse regulation of angiogenesis for the traditional Chinese medicine for promoting blood circulation and removing blood stasis on the basis of the known treatment of ischemic diseases.Provide a new perspective and theoretical basis for the use of Danshen and Chuanxiong medicine in clinical cancer patients.Reveal the material basis and mechanism of angiogenesis effect of Danshen-chuanxiong herb-partners.
出处 《Journal of Hainan Medical University》 2022年第9期48-55,共8页 海南医学院学报(英文版)
基金 Fund Project:Outstanding Doctoral Graduates of Shanxi University of Traditional Chinese Medicine Come to Shanxi to Work,Reward Funds,Scientific Research Start-Up Fund Project(No.2020BKS06)。
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