OBJECTIVE To investigate the mechanism of Phyllanthus emblica L. in the prevention and treatment of alcoholic liver disease(ALD) based on network pharmacology and molecular docking, with verification through animal experiments.

METHODS The main effective chemical components and targets of Phyllanthus emblica L. were obtained and screened from TCMSP, HERB and Uniprot database, and ALD related targets were gained from the OMIM and GeneCards database. The Venn was used to obtain the overlapping targets of Phyllanthus emblica L. and ALD, and construct a protein interaction network using the String database for the overlapping targets. Based on the Metascape online website, the enrichment analysis of GO and KEGG pathway was carried out on the core targets. Cytoscape was applied to construct the network map of the “active ingredients-targets-pathyway-disease” for the protective effect of Phyllanthus emblica L. on ALD. The key components and core proteins were docked and visualized by AutoDock Tools and PyMOL. Secondly, to establish the chronic alcoholic liver injury mouse model, to verify the predictive results of network pharmacology and molecular docking through HE staining, enzyme-linked immunosorbent assay(ELISA), immunohistochemistry, quantitative real-time PCR(qPCR) and Western blotting.

RESULTS Network pharmacology showed that there were 248 targets of Phyllanthus emblica L. protecting ALD. The enrichment of GO and KEGG analysis showed that the protein binding, PI3K/AKT, TNF signaling pathway and other processes was active. The molecular docking showed that AKT1 was the key core target of Phyllanthus emblica L. in the prevention and treatment of ALD. In the alcoholic liver injury mouse model, freeze-dried powder from Phyllanthus emblica L. could effectively decreased the activities of AST, ALT, ALP, TNF-α, and CYP2E1, down-regulated the expression of α-SMA, PI3K mRNA and AKT mRNA , while it improved the expression of ADH, ALDH, and IL-10. HE staining showed that freeze-dried powder from Phyllanthus emblica L. could significantly reduce the phenomenon of lipid aggregation in the liver, and the morphology of hepatocytes returned to normal. Moreover, the results of Western blotting confirmed that it could significantly decrease the expression of the core target p-AKT1.

CONCLUSION The protection of Phyllanthus emblica L. against ALD is through the interaction of multi-component, multi-target, and multi-pathway, and its underlying mechanism may be related to the activation of PI3K/AKT signaling pathway and the inhibition of inflammatory response.