Prediction of potential mechanism of curcumin combined with berberine in improving drug-induced liver injury based on network pharmacology
Objective The potential mechanism of curcumin(CUR)combined with berberine(BBR)in improving drug-induced liver injury(DILI)was preliminarily predicted by a method of in vivo experiment in combination with network pharmacology.Methods The animal model was established by acetaminophen(APAP)-induced DILI and the levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were detected in serum of mice.The network pharmacological approach was used to collect related targets of CUR,BBR,and DILI;Wayne mapping was carried out to screen intersection targets,followed by establishment of a protein-protein interaction(PPI)network of CUR-BBR-DILI.Functional enrichment analysis of gene ontology(GO)and pathway enrichment analysis of Kyoto Encyclopedia of Genes and Genomes(KEGG)were conducted finally.Results The in vivo experimental results showed that the combination of CUR and BBR can significantly reduce the serum ALT and AST levels in mice,which is better than administration alone;Network pharmacology experiment results exhibited that 291 related targets of CUR and 208 related targets of BBR were collected by PharmMapper database,and 904 related targets of DILI were collected by Genecards database;77 intersection targets were screened by Venny 2.1.0 database;52 gene functions and 20 signal pathways possibly in connection with the improvement of DILI via drug combination were obtained by GO and KEGG analysis,respectively;nine of the top ten core targets according to degree in PPI network were enriched to PI3K/AKT signaling pathway,which were in order as follows:SRC,EGFR,HSP90AA1,IGF1,HRAS,MAPK14,ESR1,CASP3,and PTK2.Conclusion DILI might be synergistically improved by CUR combined BBR through multi-target and multi-pathway manner,providing a theoretical basis for the elucidation of the mechanism of drug combination against DILI.
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