Products Cited in Publications Worldwide Synergistic Dual-Pathway Mechanism of Myricetin in Alleviating Bisphenol S-Induced Oxidative Stress and Lipid Metabolic Disruption in Caenorhabditis elegans

Synergistic Dual-Pathway Mechanism of Myricetin in Alleviating Bisphenol S-Induced Oxidative Stress and Lipid Metabolic Disruption in Caenorhabditis elegans

Cao, Hui; Zhang, Jingjing; Shan, Yumin; Wang, Yangyang; Hou, Xiaojie; Liu, Yi; Zhang, Haolin; Cassani, Lucia; Wang, Hui

Abstract

Bisphenol S (BPS) is increasingly used as a substitute for BPA, but has raised serious concerns due to its environmental persistence and potential health risks. In this study, environmental exposure to BPS results in significant bioaccumulation and induces oxidative stress and lipid metabolic disturbances in Caenorhabditis elegans have been demonstrated firstly. Importantly, we identify , a natural flavonoid, as an effective protective agent that mitigates BPS-induced toxicity. Mechanistically, this study revealed that alleviates BPS-induced toxicity through a synergistic "dual-pathway" mechanism involving the regulation of both the AMPK/FOXO and AMPK/mTOR signaling pathways firstly. Specifically, upregulates the energy sensor aak-2, thereby activating the AMPK/FOXO cascade, which promotes via increased lgg-1 expression and facilitates the nuclear translocation of the transcription factor daf-16. This leads to the transcriptional upregulation of downstream defense genes (sod-3, ctl-2, gst-4) and the regulation of lipid metabolism through sbp-1. Concurrently, enhances autophagic flux via activation of the AMPK/mTOR pathway. Notably, the inhibitor compound C only partially suppresses these effects suggests the involvement of additional AMPK-independent mechanisms. These findings uncover a novel dual-pathway mechanism by which alleviates BPS toxicity and highlight the potential of natural compounds in mitigating environmental pollutant-induced metabolic disorders.

Keywords

Caenorhabditis elegans ; ; Bisphenol S ; ; DAF-16/FOXO ; Lipid metabolism

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Dorsomorphin

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