Network toxicology and molecular docking to elucidate the mechanisms of intestinal toxicity induced by P-phenylenediamine antioxidants and their quinone derivatives

P-phenylenediamines (PPDs) and their quinone derivatives (PPDQs), emerging pollutants widespread in urban environments, exhibit biotoxicological risks. Epidemiological studies suggest their adverse impacts on intestinal health, yet underlying mechanisms remain unclear. The aim was to investigate the potential mechanisms of enterotoxicity of 15 PPDs and PPDQs using molecular docking and network toxicology approaches. 182 potential targets connected to PPD- and PPDQ-induced enterotoxicity were identified through the SuperPred, STITCH, GeneCards, and OMIM databases. 30 hub targets, including SRC, EGFR, CASP3, and others, were obtained using the STRING and Cytoscape tools. GO and KEGG enrichment analyses through the DAVID and FUMA databases, demonstrated significant enrichment of core enterotoxicity-related targets in cancer-associated pathways and the MAPK signaling pathway. Molecular docking via AutoDock confirmed strong binding between PPDs/PPDQs and the core targets. The results suggest that PPDs and PPDQs may contribute to the onset and progression of bowel cancer and enteric-related inflammation. They achieve this by influencing cancer cell death and proliferation. Moreover, they trigger inflammatory signaling pathways. This research offers a theoretical framework for elucidating the molecular mechanisms underlying enterotoxicity caused by PPDs and PPDQs, which is beneficial for the prevention of associated diseases.