In Silico Analysis Identifies the Anti-Liver Injury Targets of Diammonium Glycyrrhizinate: Validated in Perfluorooctanoic Acid-Lesioned Mouse Model.

Abstract

Liver injury refers to a pathological condition that causes dysfunction to hepatic parenchymal cells. And diammonium glycyrrhizinate (DG) is clinically prescribed for hepatoprotection. To date, detailed information regarding DG against liver injury in molecular mechanisms remains unrevealed totally. In the present study, we applied network pharmacology and molecular docking to decipher substantial genes, biological functions of DG for treating liver injury. Furthermore, preclinical experiments using perfluorooctanoic acid (PFOA)-induced liver injury in mice were used to validate the bioinformatic findings. Our results showed that the target network of DG and liver injury predominantly shared 90 genes. Eleven core genes of DG treating liver injury including ALB, TP53, TNF, CASP3, PTGS2, JUN, TLR4, IL10, STAT3, NOS3, FOS. The gene ontology and KEGG enrichment further highlighted their importance in regulation of cell proliferation, regulation of transcription, inflammatory response, regulation of NF-kappaB import into nucleus, regulation of apoptotic process, T cell receptor signaling pathway, and Toll-like receptor signaling pathway. Moreover, DG treatment was found to rescue the PFOA-induced liver injury through the modulation of identified genes including TNF, CASP3, PTGS2, and ALB. Current integrated data from bioinformatics method and experimental validation uncovered that DG exerts potent actions to treat liver injury through regulating core targets associated with inflammation and immunomodulation.