Network Toxicology and Molecular Docking Reveal Diethyl Phthalate as a Potential Epigenetic Modulator in Psoriasis Pathogenesis

Diethyl phthalate (DEP), a widely used phthalate ester, is extensively detected in environmental and human biological samples, indicating significant exposure through ingestion, inhalation, and dermal absorption. Psoriasis, a chronic inflammatory skin disease, is characterized by immune dysregulation and epigenetic alterations. However, the potential contribution of DEP to psoriasis pathogenesis remains poorly understood. This study employed a network toxicology approach, integrating protein-protein interaction (PPI) network analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and molecular docking to systematically evaluate the potential role of DEP in psoriasis. A total of 47 intersecting genes were identified between DEP targets and psoriasis-related genes. Key hub genes, including SIRT1, HDAC1, BRD4, EP300, and EZH2, were identified, highlighting their possible involvement in DEP-mediated toxicity. Enrichment analysis revealed significant associations with apoptosis, chromatin remodeling, and immune regulation. Molecular docking results demonstrated strong binding affinities between DEP and core proteins, particularly SIRT1. These findings suggest that DEP may exacerbate psoriasis through epigenetic modulation and immune dysregulation. This study provides a novel mechanistic link between environmental exposure and inflammatory skin disease and underscores the need for further experimental validation.