A food-derived flavonol, myricetin, mitigates bisphenol S-associated metabolic dysfunction and partial...

Myricetin (MYR), a dietary flavonol abundant in fruits, vegetables, and tea, has recognized for its metabolic regulatory activity, but whether it can mitigate contaminant-associated metabolic dysfunction remains unclear. In this study, a bisphenol S (BPS)-exposed Caenorhabditis elegans (C. elegans) model was established to evaluate the protective effects of MYR and to examine whether parental MYR intervention influences metabolic phenotypes in subsequent generations. MYR attenuated BPS-associated lipid accumulation, oxidative stress, ATP depletion, and locomotor impairment, accompanied by reduced ROS and MDA levels, increased SOD activity and ATP content, and decreased LGG-1::GFP puncta accumulation. Transcriptomic profiling showed that MYR reshaped and partially restored BPS-associated transcriptional changes related to lipid metabolism and stress adaptation. Genetic, reporter-based, and pharmacological analyses supported the involvement of an AAK-2/DAF-16-associated response in MYR-mediated protection. In addition, parental MYR treatment partially reduced inherited lipid accumulation in F1 and F2 offspring, and maintenance of this benefit was largely dependent on descendant DAF-16 activity. Collectively, these findings support MYR as a food-derived bioactive with the potential to mitigate contaminant-associated metabolic dysfunction and provide a mechanistically informed basis for future nutritional intervention studies.