基于网络毒理学和分子对接探讨双酚S、双酚E和双酚AF诱导神经毒性的协同作用机制OA

OBJECTIVE:To investigate synergistic mechanisms through which bisphenol analogues—bisphenol S(BPS),bisphenol E(BPE),and bisphenol AF(BPAF)—induced neurotoxicity,and to provide a scientific foundation for evaluating their health risks.METHODS:Target genes for BPS,BPE,and BPAF were retrieved from four databases,including ChEMBL.Venn diagram analysis was performed to identify common targets,followed by intersection with neurotoxicity-related targets from the GeneCards database.Functional enrichment analysis of these intersected targets was conducted using the DAVID database,with results visualized in R.A protein-protein interaction(PPI)network was constructed using STRING,and network analysis was performed via Cytoscape.The CytoHubba plugin was used to calculate maximum cluster centrality(MCC)values,and the top 10 targets ranked by both degree centrality and MCC were selected as core targets.The 3D structures of BPS,BPE,and BPAF were obtained from the PubChem database,while the crystal structures of core target proteins were retrieved from PDB.Molecular docking was performed using the CB-Dock2 and visualized in PyMOL.RESULTS:The common targets of neurotoxicity induced by BPS,BPE,and BPAF were significantly enriched in pathways such as MAPK.Core targets included ALB,TNF,CASP3,ESR1,IGF1,EGFR,MMP9,and SRC.All three bisphenols exhibited strong binding affinities(Vina scores<-6 kcal/mol),with BPAF showing greater affinity than BPS and BPE.CONCLUSION:BPS,BPE,and BPAF induced neuroinflammation and apoptosis through synergistic regulation of multiple pathways,including MAPK,thereby leading to neurotoxicity.Among them,BPAF demonstrated stronger effects,highlighting its increased neurotoxic risk.