Mechanism of action of Zhige Baogan Jiangzhi prescription in treatment of alcoholic liver disease:A study based on network pharmacology and in vitro experiments
Objective:To investigate the possible mechanism of action of Zhige Baogan Jiangzhi prescription in the treatment of alcoholic liver disease(ALD)based on network pharmacology and in vitro experiments.Methods:The potential effective constituents of Zhige Baogan Jiangzhi prescription were obtained,and the core targets and pathways were validated based on the protein-protein interaction network,gene ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis,molecular docking,and experi-mental study.The methods such as HE pathological staining,ELISA,PCR,and Western blot were used to investigate the effect of Zhige Baogan Jiangzhi prescription on related indicators in liver tissue and serum of ALD rats.Results:A total of 321 targets of Zhige Baogan Jiangzhi prescription and 1 635 ALD-related genes were obtained,with 178 inter-secting genes and 15 core targets.The core targets included ACTB and IL-6.GO functions mainly involved various bio-logical processes such as regulation of external biological stimulus,oxidative stress,and peptide response,and KEGG pathways were mainly enriched in the PI3K/Akt signaling pathway,the TNF signaling pathway,and the IL-17signaling pathway.Puerarin and luteolin might be the core active compounds of Zhige Baogan Jiangzhi prescription in the treat-ment of ALD.HE staining showed that the model group had disordered arrangement and necrosis of hepatocytes,with a large amount of lipid droplet vacuoles,and compared with the model group,each treatment group had varying degrees of improvement in liver lesions.There were significant differences in the protein and mRNA expression levels of IL-6 and TNF-α and the protein expression levels of PI3K,p-PI3K,AKT,and p-AKT between the model group and the normal group,as well as between the metadoxine group and each traditional Chinese medicine group(P<0.01 or P<0.05).Con-clusion:Zhige Baogan Jiangzhi prescription exerts a therapeutic effect on ALD through multiple components,targets,and signaling pathways,possibly by upregulating the expression levels of p-PI3K and p-AKT and inhibiting inflammation.