Assessing cardiac insufficiency risks of aflatoxin B1 through network toxicology and molecular docking analyses.

This study aimed to elucidate the promoting effect of Aflatoxin B1 (AFB1) on cardiac insufficiency and its specific molecular mechanisms through methods including network toxicology, molecular docking, dynamics simulation, and in vivo experiments. A total of 44 overlapping targets between cardiac insufficiency and AFB1 toxicity were identified. Subsequently, a PPI network was constructed using STRING and Cytoscape software, and 12 core genes were identified, including AKT1, HIF1A, MMP9, PIK3CA, NFKB1, GSK3B, TLR4, KDR, JAK2, MAPK1, PIK3R1, and PTPN11. GO and KEGG enrichment analyses demonstrated that AFB1-induced cardiac insufficiency is primarily linked to the activation of the PI3K-AKT and MAPK signaling pathways. Molecular docking results showed that AFB1 exhibited strong binding affinity with all 12 core targets, among which its binding ability to JAK2, GSK3B, and MMP9 ranked as the top three. Molecular dynamics simulations focused on the complex formed between AFB1 and JAK2, confirming its favorable stability. Additional murine experiments confirmed that AFB1 exposure induces cardiac insufficiency and activates the PI3K-AKT and MAPK signaling pathways. These findings collectively demonstrate that AFB1 binding to JAK2 activates both the PI3K-AKT and MAPK pathways, consequently promoting cardiac insufficiency. By elucidating the underlying molecular mechanisms, this study establishes a theoretical framework for understanding how chronic AFB1 exposure aggravates cardiac insufficiency.