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Peer-reviewedCC BY-NC-NDInflammation

Genistein Has Beneficial Effects Against Non-Alcoholic Fatty Liver Disease Through Activation of the SIRT1/PPAR-α/PGC-1α and Nrf2 Signaling Pathways.

  • Fahimeh Zamani-Garmsiri1
  • Golnaz Goodarzi2
  • Sadra Samavarchi Tehrani3
  • ShadiSadat Seyyedebrahimi1
  • Arash Bahramzadeh1
  • Reza Meshkani4
4 affiliations
  1. 1Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
  2. 2Department of Pathobiology and Laboratory Sciences, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran.
  3. 3Endocrine Research Center, Institute of Endocrinology and Metabolism, University of Medical Sciences, Tehran, Iran.
  4. 4Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran. [email protected].
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Abstract

The development of fatty liver has been associated with hepatic metabolic derangements. Genistein has been reported to be a treatment option for Non-alcoholic fatty liver disease (NAFLD). In this study, we evaluated the effect of genistein on hepatic steatosis through the silent mating type information regulation 2 homolog - 1 (SIRT1)/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)/peroxisome proliferator-activated receptor α (PPARα) and Nrf2 signaling pathways in mice fed a high-fat diet (HFD). After 10 weeks of HFD feeding, the mice were randomly divided into the HFD and genistein (0.2%) groups. Genistein treatment significantly decreased liver weight and lipid accumulation in the liver of the HFD group. The mRNA level of PPARα, the acetylation of PGC-1α, mRNA, and protein levels of SIRT1 was increased in the genistein group compared with the HFD group. Genistein supplementation could enhance total antioxidant capacity, total thiol content and decrease protein carbonyl and malondialdehyde (MDA) levels in the liver of mice fed HFD. In addition, the mRNA and protein levels of Nrf2, HO-1, and SOD2 were enhanced in the liver of HFD-fed mice. These findings suggest that genistein has favorable impacts against NAFLD via activation of the SIRT1/PGC1α/PPARα and Nrf2 signaling pathways.

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Cite

BibTeXRIS
BibTeX
@article{zamanigarmsiri2026genistein,
  title = {{Genistein Has Beneficial Effects Against Non-Alcoholic Fatty Liver Disease Through Activation of the SIRT1/PPAR-α/PGC-1α and Nrf2 Signaling Pathways.}},
  author = {Fahimeh Zamani-Garmsiri and Golnaz Goodarzi and Sadra Samavarchi Tehrani and ShadiSadat Seyyedebrahimi and Arash Bahramzadeh and Reza Meshkani},
  journal = {Inflammation},
  year = {2026},
  month = jul,
  doi = {10.1007/s10753-025-02396-0},
  url = {https://europepmc.org/article/MED/42905287},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Genistein Has Beneficial Effects Against Non-Alcoholic Fatty Liver Disease Through Activation of the SIRT1/PPAR-α/PGC-1α and Nrf2 Signaling Pathways.
AU  - Fahimeh Zamani-Garmsiri
AU  - Golnaz Goodarzi
AU  - Sadra Samavarchi Tehrani
AU  - ShadiSadat Seyyedebrahimi
AU  - Arash Bahramzadeh
AU  - Reza Meshkani
PY  - 2026
DA  - 2026/07/25
JO  - Inflammation
DO  - 10.1007/s10753-025-02396-0
UR  - https://europepmc.org/article/MED/42905287
AB  - The development of fatty liver has been associated with hepatic metabolic derangements. Genistein has been reported to be a treatment option for Non-alcoholic fatty liver disease (NAFLD). In this study, we evaluated the effect of genistein on hepatic steatosis through the silent mating type information regulation 2 homolog - 1 (SIRT1)/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)/peroxisome proliferator-activated receptor α (PPARα) and Nrf2 signaling pathways in mice fed a high-fat diet (HFD). After 10 weeks of HFD feeding, the mice were randomly divided into the HFD and genistein (0.2%) groups. Genistein treatment significantly decreased liver weight and lipid accumulation in the liver of the HFD group. The mRNA level of PPARα, the acetylation of PGC-1α, mRNA, and protein levels of SIRT1 was increased in the genistein group compared with the HFD group. Genistein supplementation could enhance total antioxidant capacity, total thiol content and decrease protein carbonyl and malondialdehyde (MDA) levels in the liver of mice fed HFD. In addition, the mRNA and protein levels of Nrf2, HO-1, and SOD2 were enhanced in the liver of HFD-fed mice. These findings suggest that genistein has favorable impacts against NAFLD via activation of the SIRT1/PGC1α/PPARα and Nrf2 signaling pathways.
SN  - 0360-3997
SN  - 1573-2576
ER  -