Analysis of the toxicological effects of Calycosin to alleviate diethyl phthalate exposure on cognitive impairment by network toxicology and chemical bioinformatics

Diethyl phthalate (DEP), a synthetic plasticizer ubiquitously employed in personal care products and food packaging materials, demonstrates pronounced neurotoxic properties. However, the mechanism underlying its neurotoxicity remains unclear. First, ProTox3.0 was employed to predict toxicity profiles of environmental contaminants (DEP), followed by comprehensive network toxicology analysis to identify pivotal target proteins and perform functional enrichment investigations. Then, network pharmacology analysis elucidated potential therapeutic targets within Astragalus exhibiting neuroprotective efficacy against DEP-induced cognitive dysfunction. Following MCODE network analysis and molecular docking screening, PLCG1 was identified as the core target. Next, molecular docking simulations targeting PLCG1 facilitated the screening of bioactive constituents from Astragalus membranaceus, and a random forest model based on the cognitive dysfunction compound database was constructed to identify effective compounds. Finally, the neuroprotective potential of Calycosin was preliminarily assessed by molecular dynamics simulation and in vitro experiments. In conclusion, Calycosin may ameliorate the toxic effects of DEP exposure on cognitive impairment. This study provides a theoretical basis for the toxic mechanisms and prevention of cognitive impairment induced by DEP.