Exploring the Mechanism of Cichorium Glandulosum in the Treatment of Liver Fibrosis Based on Network Pharmacology and Experimental Validation
OBJECTIVE To investigate the mechanism of Cichorium glandulosum in the treatment of liver fibrosis by using network pharmacology and experimental validation.METHODS A"component-target-pathway"network was constructed with the help of TCMSP,Pubchem,SwissTargetPrediction and Genecards databases,and the STRING database was used to predict the targets of Cichorium glandulosum against liver fibrosis.KEGG and GO enrichment analysis was performed in the DAVID database,and molecular docking of active ingredients and key targets was docked in AUTODOCK.PDGF-BB was used to induce activation of cells and verify the effects of six compounds,including quercetin,quercetin,chicoric acid,caffeic acid,chlorogenic acid,and isochlorogenic acid,on the proliferation,apoptosis,and liver fibrosis indicators of HSC-T6 cells.Western blotting was used to detect the expression of Ras,ERK1,ERK2,C-fos,and JNK proteins in HSC-T6 cells.RESULTS Network pharmacology screened 239 common targets between the components and liver fibrosis,PPI analysis showed that SRC,STAT3,HSP90AA1 and other targets were key targets,KEGG analysis showed that the pathways affected by Cichorium glandulosum included cancer pathways,metabolic pathways,etc.GO analysis predicted that Cichorium glandulosum mainly affected processes such as signal transduction.The molecular docking results showed that the target that could bind well with the components MAPK1,and the components that could bind well with the target aesculetin,caffeic acid and chlorogenic acid.Compared with the model group,the inhibition effect of the six compounds on PDGF-BB-induced HSC-T6 cell activation was stronger,and all 6 compounds had the effects to reverse the index of liver fibrosis,in which aesculetin had the strongest activity(P＜0.01).The expression of Ras,ERK1,ERK2,C-fos,and JNK in HSC-T6 cells decreased after the interventions of 6 compounds.CONCLUSION Each component of Cichorium glandulosum has different anti liver fibrosis effects,which are related to the inhibition of ERK/RAS pathway activation.
万方数据
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