Objective:To explore and verify the mechanism of Gan Dou Ling in improving liver fibrosis in Wilson disease(WD)by network pharmacology and copper loaded mice experiments.Methods:The main chemical components and corres...Objective:To explore and verify the mechanism of Gan Dou Ling in improving liver fibrosis in Wilson disease(WD)by network pharmacology and copper loaded mice experiments.Methods:The main chemical components and corresponding gene targets of each drug in Gan Dou Ling were obtained by using TCMSP database.The database of gene mutation and disease related gene was searched through the GeneCards database,DrugBank database,PharmGKB database and the DisGeNET database.After the intersection of drug and disease target genes.The STRING website was used to analyze the protein-protein interaction degree of target genes,and import the data to Cytoscape software 38.2 to analyze protein interaction network.The GO databases and KEGG databases were obtained in R language for enrichment analysis.On this basis,Masson staining were used to observe the degree of liver fibrosis in copper loaded mouse model,and the results of network pharmacological analysis were verified by Western Blot(WB).Results:A total of 108 drug disease intersection genes were analyzed by network pharmacology.Through PPI network analysis,JUN was found to be the key genes.The enrichment analysis of KEGG pathway showed that MAPK signal pathway was the important potential target pathways.Animal experiments showed that Gan Dou Ling could reduce liver fibrosis and inhibit the phosphorylation of P38,JNK and C-JUN in copper loaded mice.Conclusion:Gan Dou Ling may achieve the effect of treating WD liver fibrosis by inhibiting P38/JNK signaling pathway.展开更多
基金supported by the National Natural Science Foundation of China(No.81973825)the Natural Science Research Foundation of Anhui Province Universities(No.KJ2020A0436)。
文摘Objective:To explore and verify the mechanism of Gan Dou Ling in improving liver fibrosis in Wilson disease(WD)by network pharmacology and copper loaded mice experiments.Methods:The main chemical components and corresponding gene targets of each drug in Gan Dou Ling were obtained by using TCMSP database.The database of gene mutation and disease related gene was searched through the GeneCards database,DrugBank database,PharmGKB database and the DisGeNET database.After the intersection of drug and disease target genes.The STRING website was used to analyze the protein-protein interaction degree of target genes,and import the data to Cytoscape software 38.2 to analyze protein interaction network.The GO databases and KEGG databases were obtained in R language for enrichment analysis.On this basis,Masson staining were used to observe the degree of liver fibrosis in copper loaded mouse model,and the results of network pharmacological analysis were verified by Western Blot(WB).Results:A total of 108 drug disease intersection genes were analyzed by network pharmacology.Through PPI network analysis,JUN was found to be the key genes.The enrichment analysis of KEGG pathway showed that MAPK signal pathway was the important potential target pathways.Animal experiments showed that Gan Dou Ling could reduce liver fibrosis and inhibit the phosphorylation of P38,JNK and C-JUN in copper loaded mice.Conclusion:Gan Dou Ling may achieve the effect of treating WD liver fibrosis by inhibiting P38/JNK signaling pathway.
