Computational Study Links BPA to Liver Disease Targets

Researchers from Bishan Hospital of Chongqing Medical University and Binzhou Institute of Technology have published a study in Frontiers in Pharmacology that identifies specific molecular targets and signaling pathways linking bisphenol A (BPA) to metabolic dysfunction-associated steatotic liver disease (MASLD). The study, led by Chengyong Tang and colleagues, utilized an integrated computational approach combining network toxicology and molecular docking to explore the underlying mechanisms of BPA-induced hepatotoxicity. While BPA is widely recognized as a ubiquitous endocrine-disrupting chemical associated with metabolic disorders, the precise molecular mechanisms driving its contribution to liver disease have remained elusive until now.

The research team began by screening multiple databases to identify targets associated with both BPA exposure and MASLD. This initial screening yielded 886 BPA-related targets and 3,109 MASLD-related targets. By analyzing the intersection of these two sets, the researchers identified 451 common targets. To further narrow down the most significant contributors, the team employed a protein-protein interaction (PPI) network analysis. Using the Cytoscape Molecular Complex Detection (MCODE) plugin, they screened for core targets within this network, ultimately identifying 16 key targets. These core targets included JUN, IL6, TNF, and TLR4.

To validate the computational findings, the study utilized the GSE163211 dataset from the Gene Expression Omnibus (GEO) repository for external validation. The validation confirmed that several of the core targets exhibited significantly upregulated expression in MASLD samples, with statistical significance indicated by a P-value of less than 0.05.

Following the identification and validation of core targets, the researchers conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to understand the biological functions and pathways involved. The GO enrichment analysis revealed that the core targets were primarily involved in transcriptional regulation, protein binding, and intracellular structural processes. The KEGG enrichment analysis highlighted specific signaling pathways, notably the PI3K-Akt, FoxO, and cellular senescence pathways.

The study further employed molecular docking simulations to verify the physical interaction between BPA and the identified core targets. The results showed that BPA bound strongly to six key core targets. The binding energies for these interactions ranged from -5.3 to -8.2 kcal/mol.

The integration of network toxicology and molecular docking in this study establishes a comprehensive computational framework for assessing the risks of environmental hepatotoxicants.

While the findings provide a detailed theoretical basis for understanding BPA-induced MASLD, they do not constitute direct experimental proof of causality in human subjects. The study provides a theoretical foundation for regulatory policy formulation regarding BPA exposure and for mechanistic research into MASLD.

The study’s identification of specific core targets and pathways offers a structured approach for future research, moving beyond general associations to specific molecular mechanisms.

Subject of Research: Computational identification of molecular targets and pathways linking bisphenol A to MASLD

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

Article References: Li, Y., Xiong, Z., Zhang, Y., & Tang, C. (2026). Network toxicology, molecular docking and in vitro validation reveal the molecular mechanisms of bisphenol A-induced MASLD. Frontiers in Pharmacology, 17, Article 1905217. https://doi.org/10.3389/fphar.2026.1905217

Image Credits: AI Generated

DOI: 10.3389/fphar.2026.1905217

Keywords: bisphenol A, MASLD, network toxicology, molecular docking, hepatotoxicity, PI3K-Akt pathway, endocrine disruptors, liver disease, Network, toxicology, molecular, docking