Mechanism of bisphenol A derivatives inducing periodontitis based on network toxicology and molecular dynamics

Fu Haoxuan; Mao Zhouhong; Han Li; Zhang Chao; Zheng Yanyan; Peng Jiakuan; Tang Wanrong

doi:10.11986/j.issn.1673-873X.2025.08.06

Abstract：Objective To explore the mechanism of bisphenol A glycidyl methacrylate(Bis-GMA)derivatives in inducing pe-riodontitis based on network toxicology and molecular dynamics.Methods The Swiss Target Prediction database was used to screen potential targets for Bis-GMA.Periodontitis-related targets were obtained from GeneCards,Online Mendelian In-heritance in Man(OMIM),and Therapeutic Target Database(TTD)databases.The intersection of the predicted targets of Bis-GMA and periodontitis-related targets was used to construct the network.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed using DAVID,and a PPI network was constructed u-sing STRING.Core targets were identified using Cytoscape.Molecular docking was performed using AutoDock,and molec-ular dynamics simulations were carried out using GROM ACS.Results A total of 1,503 periodontitis-related disease targets were obtained by searching"periodontitis"in the database.Using Swiss Target Prediction,94 potential targets for Bis-GMA were identified.The intersection of the targets of Bis-GMA and periodontitis resulted in 29 targets,and a toxicology-target-disease network diagram was constructed.GO enrichment analysis showed that the Bis-GMA intervention targets for peri-odontitis mainly involve biological processes such as response to lipopolysaccharides,reaction to bacterial-derived molecules,and positive regulation of protein phosphorylation.KEGG enrichment analysis revealed that the main pathways involved in Bis-GMA's intervention in periodontitis are the regulation of transient receptor potential(TRP)channels by inflammatory mediators,the tumor necrosis factor(TNF)signaling pathway,and pathways related to lipid metabolism and atherosclero-sis.Molecular docking results indicated that Bis-GMA can stably bind to serine/threonine kinase 1(AKT1),phosphatidyli-nositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3CA),heat shock protein 90 alpha class A member 1(HSP90AA1),mammalian target of rapamycin(MTOR),matrix metalloproteinase-9(MMP9),non-receptor tyrosine ki-nase(SRC),phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta(PIK3CD),and mitogen-activated pro-tein kinase 8(MAPK8).Conclusion Bis-GMA may induce periodontitis by regulating multiple targets and pathways,medi-ating immune-inflammatory responses,apoptosis,and bone metabolism imbalance.