Efficient evaluation of osteotoxicity and mechanisms of endocrine disrupting chemicals using network toxicology and molecular docking approaches: triclosan as a model compound.

This study aimed to demonstrate the utility of a network toxicology strategy in elucidating osteotoxicity and the molecular mechanisms of endocrine-disrupting chemicals (EDCs) using triclosan exposure in postmenopausal osteoporosis (PMOP) as a case study. The potential targets of triclosan were identified using the Comparative Toxicogenomics Database, SwissTargetPrediction, and TargetNet. PMOP-related targets were obtained from GeneCards, DisGeNET, and DrugBank. A total of 478 overlapping genes between disease targets and triclosan effectors were identified. Subsequent analysis using STRING and Cytoscape, applying the Matthews correlation coefficient algorithm, identified five core genes: STAT3, TP53, EGFR, MYC, and JUN. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses performed using R revealed that triclosan-induced PMOP is primarily associated with disrupted endocrine signaling and activation of the Phosphoinositide 3-kinase (PI3K)-Protein kinase B (Akt) signaling pathway. Molecular docking using CB-Dock2 confirmed strong binding affinities between triclosan and the core targets. Collectively, these results indicate that triclosan adversely affects bone health by disrupting endocrine regulation and energy metabolism through the PI3K-Akt pathway. This study establishes a theoretical framework for understanding how long-term triclosan exposure induces or exacerbates PMOP by investigating the underlying molecular mechanisms. These findings present a novel paradigm for evaluating the health risks posed by environmental pollutants.