Exploring potential mechanisms of artificial sweeteners in polycystic ovary syndrome through network toxicology and molecular docking

Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder increasingly prevalent among women of reproductive age. Artificial sweeteners, commonly used as sugar substitutes, are now under scrutiny for their potential disruption of metabolic and hormonal equilibrium. This investigation delves into the molecular mechanisms through which seven artificial sweeteners (aspartame, saccharin, sucralose, acesulfame-K, sodium cyclamate, neotame, and alitame) may impact the development of PCOS. By employing network toxicology and molecular docking methodologies, we identified 85 common targets shared between genes associated with sweeteners and those linked to PCOS. Enrichment analyses using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways unveiled connections to inflammation, insulin resistance, and steroid biosynthesis, particularly implicating pathways such as TNF signaling, AGE-RAGE signaling, and the AMPK pathway. Notably, key targets like TNF, STAT3, and IFNG displayed high binding affinities with artificial sweeteners in molecular docking simulations. These results suggest a potential role for artificial sweeteners in exacerbating PCOS progression through inflammatory and metabolic pathways, underscoring the need for further experimental validation.