RESUMO
ObjectiveTo predict the molecular mechanism of resveratrol against non-alcoholic fatty liver disease （NAFLD） based on network pharmacology and molecular docking and verify the results on the liver cell model induced by PM2.5 exposure. MethodThe targets of resveratrol were screened out from Traditional Chinese Medicine System Pharmacology Database and Analysis Platform （TCMSP）， PubChem， DrugBank， and SwissTargetPrediction， and the potential targets of NAFLD were retrieved from Comparative Toxicogenomics Database （CTD）， DisGeNET， GeneCards， and Online Mendelian Inheritance in Man （OMIM）. Then the common targets were obtained. STRING 11.5 was used to construct the protein-protein interaction （PPI） network of the common targets. Cytoscape 3.8.2 was used to plot the “target-pathway” network， and the core modules and key targets were selected. Metascape was adopted for Gene Ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） enrichment analyses of common targets. SYBYL-X 2.0 was used for molecular docking of resveratrol to key targets. Finally，cell apoptosis and the expression of apoptosis-related proteins were detected by flow cytometry and Western blot in the PM2.5-exposed human liver cell line （HepG2）. ResultA total of 115 common targets of resveratrol and NAFLD were obtained. The key targets included tumor necrosis factor （TNF）， B-cell lymphoma-2 （Bcl-2）， and cysteinyl aspartate-specific protease-3（Caspase-3）. As revealed by KEGG enrichment analysis， 174 signaling pathways， represented by the apoptosis and TNF signaling pathways， were obtained. Molecular docking results showed that resveratrol had strong binding activities to Bcl-2 and Caspase-3. Furthermore，the results of flow cytometry and Western blot demonstrated that resveratrol inhibited cell apoptosis of PM2.5-exposed HepG2 cells by regulating the protein expression of Bcl-2 and Caspase-3. ConclusionResveratrol can treat NAFLD in a multi-pathway and multi-target way. It mainly inhibits liver cell apoptosis by affecting the expression of Bcl-2 and Caspase-3， which provides a theoretical basis for the follow-up research on the anti-NAFLD mechanism of resveratrol.