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Flazin as a Promising Nrf2 Pathway Activator.

Hirotoshi Fuda1, Satoshi Miyanaga1, Takayuki Furukawa1

  • 1Faculty of Health Sciences , Hokkaido University , Sapporo 060-0812 , Japan.

Journal of Agricultural and Food Chemistry
|November 1, 2019
PubMed
Summary

Flazin, a compound in fermented foods, effectively activates the Keap1-Nrf2 pathway, offering significant antioxidant protection in human liver cells. This suggests flazin

Keywords:
Keap1Nrf2ORACflazinhepatocytephase II enzyme

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Area of Science:

  • Biochemistry
  • Food Science
  • Toxicology

Background:

  • Flazin is a β-carboline alkaloid found in Japanese fermented foods.
  • Oxidative stress contributes to various health disorders.
  • The Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) pathway is crucial for cellular defense against oxidative damage.

Purpose of the Study:

  • To investigate the antioxidant potential of flazin.
  • To examine flazin's effect on the Keap1-Nrf2 system in human hepatocytes.
  • To compare flazin with other antioxidant compounds.

Main Methods:

  • Chemical synthesis of flazin and its analogues.
  • Cytotoxicity assessment using IC50 values.
  • Evaluation of Keap1-Nrf2 system activation.
  • Measurement of cytoprotection against a pro-oxidant.
  • Analysis of Nrf2-dependent phase II enzyme gene and protein expression.

Main Results:

  • Flazin exhibited low cytotoxicity (IC50 < 500 μM) and superior Keap1-Nrf2 activation compared to analogues, chlorogenic acid, and curcumin.
  • Flazin demonstrated significant cytoprotection (>3-fold) against oxidative stress.
  • Flazin upregulated Nrf2-dependent genes (NQO1, GSTP) and proteins (GSH).

Conclusions:

  • Flazin possesses potent antioxidant properties by activating the Keap1-Nrf2 pathway.
  • Its strong cytoprotective effect, coupled with low lipophilicity, highlights its potential for preventing oxidation-related diseases.
  • Flazin-rich foods may contribute to health by mitigating oxidative stress.