Exploring the Mechanism of Action of Sea Buckthorn in the Treatment of Alcoholic Liver Injury Based on Network Pharmacology

Objective: To predict the mechanism of sea buckthorn in the treatment of alcoholic liver injury based on network pharmacology, and to verify the efficacy of sea buckthorn in the treatment of alcoholic liver injury by establishing an animal model of alcoholic liver injury in zebrafish. Methods: Through the traditional chinese medicine systems pharmacology (TCMSP) and Uniprot database, the effective components and their targets were collected. Venny2.1 was used to find the intersection targets. GeneCards and OMIM databases were used to collect and screen disease targets. STRING v12.0 database was used for PPI network analysis. PDB and PubChem were used to confirm protein structure and small molecular structure. The correlation network of sea buckthorn in the treatment of alcoholic liver injury was constructed by Cytoscape (Version 3.9.1) software network diagram. Gene ontology (GO) and Kyoto encyclopedia of genes (KEGG) database pathway enrichment analysis were performed on the common targets using the Metascape database. Functional verification was performed by zebrafish experiments: Wild-type AB strain zebrafish 3 days after fertilization (3 dpf) were selected. The normal group was fed with normal feeding water, and the other groups were fed in 2% anhydrous ethanol solution to establish an alcoholic liver injury model. Results: After screening, 33 active components of sea buckthorn were obtained, mainly including quercetin, sunflower, catechin and so on. There were 1434 potential targets for the treatment of alcoholic liver injury, including ADH1C, CTNNB1, TGFB1 and so on. The signaling pathways that regulate these core targets are mainly enriched in multiple signaling pathways such as lipid and atherosclerosis, fluid shear stress and atherosclerosis and PI3K-Akt signaling pathway. The results of animal experiments showed that sea buckthorn had the effect of reducing the opacity value of zebrafish liver in alcoholic liver injury model (P<0.01), improving the phenomenon of liver and yolk cyst enlargement (P<0.01), down-regulating the activity values of AST and ALT (P<0.001), improving the enlargement of liver nucleus and reducing the fatty vacuolar degeneration of liver tissue. Conclusion: Seabuckthorn can improve alcoholic liver injury, and its mechanism may be related to improving fatty acid oxidation, cell metabolism and inhibiting apoptosis.