Daidzein treatment exerts antioxidant effect via SIRT3–FOXO3a axis activation

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ID: 331764
2026
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Abstract
Abstract Metabolic dysfunction-associated progression of steatotic liver disease is closely associated with lipotoxicity-induced oxidative stress and inflammation. This study investigated whether daidzein, a major soy isoflavone, protects hepatocytes against free fatty acid-induced oxidative damage via endogenous antioxidant signaling. In HepG2 cells, daidzein treatment suppressed free fatty acid-induced reactive oxygen species (ROS) production, mitochondrial DNA fragmentation, and pro-inflammatory cytokine expression. Daidzein induced the expression of antioxidant enzymes, including MnSOD and catalase, at the transcriptional level and enhanced FOXO3a transcriptional activity. FOXO3a knockdown attenuated daidzein-induced antioxidant enzyme expression and ROS reduction. Daidzein promoted FOXO3a nuclear localization and deacetylation. Furthermore, daidzein increased SIRT3 expression levels, and SIRT3 knockdown suppressed daidzein-mediated FOXO3a activation and antioxidant effects. These findings demonstrate that daidzein attenuates lipotoxic oxidative damage by activating the SIRT3–FOXO3a axis in hepatocytes.
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openalex_W7220940457 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Takakazu Mitani, Miu Iwasaki
Journal bioscience biotechnology and biochemistry
Year 2026
DOI
10.1093/bbb/zbag152
URL
https://doi.org/10.1093/bbb/zbag152
Keywords Keywords not found

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