Network toxicology, molecular docking and in vitro validation reveal the molecular mechanisms of bisphenol A-induced MASLD

Background Bisphenol A (BPA), a ubiquitous endocrine-disrupting chemical, is associated with metabolic dysfunction-associated steatotic liver disease (MASLD), yet its underlying molecular mechanisms remain elusive. Methods This study combined network toxicology and molecular docking to explore BPA-induced hepatotoxicity targets and pathways in MASLD. BPA and MASLD-related targets were screened from multiple databases, with 886 and 3109 targets identified respectively; their intersection targets were analyzed via protein-protein interaction (PPI) network, and core targets were screened using Cytoscape Molecular Complex Detection (MCODE). The GSE163211 dataset was used for external validation of core genes, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and molecular docking verified the binding affinity between BPA and key core targets. Results We obtained 451 intersection targets, with 16 core targets (e.g., JUN, IL6, TNF, TLR4 ) identified; Gene Expression Omnibus (GEO) validation confirmed significantly upregulated expression of several core targets in MASLD samples ( P < 0.05). GO enrichment revealed involvement in transcriptional regulation, protein binding and intracellular structural processes, while KEGG enrichment highlighted the PI3K-Akt, FoxO and cellular senescence pathways. Molecular docking showed BPA bound strongly to six key core targets with binding energies ranging from -5.3 to -8.2 kcal/mol. Conclusion This study identifies the core targets and signaling pathways mediating BPA-induced MASLD, establishing an integrated computational framework for risk assessment of environmental hepatotoxicants and providing a theoretical basis for BPA regulatory policy formulation and MASLD mechanistic research.