Exploring the mechanism of Poria cocos polysaccharide against acetaminophen-induced liver injury based on network pharmacology and in vivo experiments
Objective To investigate the action targets of Poria cocos polysaccharide(PCP)against acet-aminophen(APAP)-induced liver injury by network pharmacology and in vivo experiments.Methods The action targets of Poria cocos polysaccharide were obtained through SwissTargetPrediction database,SuperPred database and Pharmmapper database.The action targets related to APAP-induced liver injury were identified by the OMIM database and GeneCards database.A protein-protein interaction(PPI)network was constructed using the String database and core targets were screened.R software was used to analyze the gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway.Molecular docking of PCP with core targets was conducted using the AutoDuck vina software.Finally,HE staining was used to evaluate the liver tissue damage in mice,and the expression of core targets was detected by RT-PCR and immunohistochemical(IHC)staining.Results A total of 26 core targets were identified.GO enrichment analysis showed that bio-logical processes such as apoptosis,cell cycle,and immune response might be involved in the process of PCP's protection against APAP-induced liver injury.KEGG enrichment analysis showed that the signaling pathways targeted by PCP against APAP-induced liver injury were mainly concentrated on the p53 signaling pathway,NOD-like receptor signaling pathway,and TNF signaling pathway.Molecular docking results showed that PCP had good binding affinity with the core targets.HE staining revealed that the morphological structure of liver tissues in the APAP group was abnormal,characterized by extensive cell necrosis,which was mitigated by PCP intervention.RT-PCR and IHC results indicated that PCP alleviated liver injury in mice by reversing the in-crease in CDK2,TNF,BCL2L1 and MAOA levels caused by APAP exposure.Conclusion Network pharma-cology and in vivo experiments have identified potential targets for PCP's protective effect against APAP-in-duced liver injury,which may be related to the regulation of the cell cycle,immune response,apoptosis,and drug metabolism.
acetaminophenchemical and pharmaceutical liver injuryPoria cocos polysaccharideprotec-tive effect
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