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Exploring the links between polyphenols, Nrf2, and diabetes: A review

Reza Ebrahimi1, Alireza Mohammadpour1, Alessandro Medoro2

  • 1Faculty of Biological Science and Technology, Department of Cell and Molecular Biology & Microbiology, University of Isfahan, Isfahan, Iran.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|April 1, 2025
PubMed

Insights

Polyphenols show promise in managing diabetes by activating the Nrf2 pathway, reducing oxidative stress, and improving insulin sensitivity. Further research is needed to overcome challenges like bioavailability for effective diabetes complication management.

Area of Science:

  • Biochemistry and Molecular Biology
  • Metabolic Disorders
  • Nutritional Science

Background:

  • Diabetes mellitus is characterized by hyperglycemia, oxidative stress, and inflammation, contributing to severe complications.
  • The Nrf2 pathway is crucial for cellular defense against oxidative damage and glucose homeostasis; its dysfunction is linked to diabetes progression.
  • Polyphenols, plant-derived compounds, are investigated for their role in modulating the Nrf2 pathway.

Purpose of the Study:

  • To explore the potential of polyphenols in modulating the Nrf2 pathway for diabetes management.
  • To review the mechanisms by which polyphenols activate Nrf2 and their effects on diabetic complications.
  • To assess the current evidence from preclinical and clinical studies regarding polyphenol efficacy in diabetes.

Main Methods:

  • Review of preclinical studies on polyphenol-induced Nrf2 activation in diabetic models.
  • Analysis of clinical trial data for polyphenols like resveratrol in diabetes management.
  • Examination of molecular mechanisms, including Keap1 interaction and epigenetic modifications.

Main Results:

  • Polyphenols activate Nrf2 through various mechanisms, reducing reactive oxygen species (ROS) and inflammation in preclinical diabetic models.
  • Some polyphenols, like resveratrol, have shown potential in improving glycemic parameters in clinical trials, though results are inconsistent.
  • Evidence suggests polyphenols can improve insulin sensitivity and attenuate inflammation associated with diabetes.

Conclusions:

  • Polyphenols demonstrate potential as a non-pharmacological approach to managing diabetes and its complications by targeting the Nrf2 pathway.
  • Challenges including bioavailability and individual response variability necessitate further research for optimizing polyphenol-based therapies.
  • Continued investigation into polyphenol mechanisms and clinical efficacy is crucial for their integration into diabetes care.
Keywords:
AutophagyDiabetesInflammationNrf2Polyphenols

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