Unraveling Berberine's Multi-Target Mechanism in Combating NAFLD: A Network Pharmacology and In Vitro Study
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Background Non-alcoholic fatty liver disease (NAFLD) poses a global health burden with limited therapies. Berberine (BBR) shows promise against NAFLD, but its molecular mechanisms remain unclear. Methods Network pharmacology predicted BBR-NAFLD intersecting targets, followed by protein-protein interaction (PPI) network construction, GO/KEGG enrichment, and molecular docking. In vitro validation used FFA-induced HepG2 steatosis cells with Oil Red O staining, triglyceride assay, and RT-qPCR. Results From 147 intersecting targets, six functional core targets were identified: AKT1, IL6, TP53, TNF, IL1B, and BCL2. Enrichment analyses implicated insulin resistance, lipid metabolism, and inflammation. Molecular docking confirmed strong BBR–core protein binding. In vitro, BBR dose-dependently reduced lipid accumulation and triglyceride levels, downregulated lipogenic (SREBP-1c) and pro-inflammatory (IL-6, IL-1β, TNF-α) genes, and restored insulin signaling (AKT1) and apoptosis-related (TP53) gene expression. Conclusion BBR ameliorates NAFLD via multi-target modulation of insulin resistance, lipogenesis, inflammation, and apoptosis, providing a systematic rationale for its therapeutic application.
