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Dietary phenolic-type Nrf2-activators: implications in the control of toxin-induced hepatic disorders

Qian Zhou1,2, Nana Zhang3, Tingyan Hu1,2

  • 1Institute for Advanced Study, Shenzhen University, Shenzhen, China. mfwang@szu.edu.cn.

Food & Function
|April 12, 2022
PubMed

Insights

Dietary polyphenols, particularly flavonoids, activate nuclear factor erythroid 2-related factor 2 (Nrf2) to combat liver disorders by reducing oxidative stress. Further research is needed to establish structure-activity relationships for these potent Nrf2 activators.

Area of Science:

  • Biochemistry
  • Toxicology
  • Nutritional Science

Background:

  • Nuclear factor erythroid 2-related factor 2 (Nrf2) activation is crucial for mitigating toxin-induced liver damage by reducing oxidative stress.
  • Dietary polyphenols are increasingly recognized as potential Nrf2 activators.
  • Identifying and characterizing these activators is vital for therapeutic development.

Purpose of the Study:

  • To review and analyze phenolic-type Nrf2 activators identified over recent decades.
  • To assess the effectiveness of these compounds based on their structural characteristics.
  • To outline the mechanisms through which these polyphenols activate Nrf2.

Main Methods:

  • Literature review of studies on phenolic Nrf2 activators.
  • Analysis of compound structures and their corresponding Nrf2-activating efficacy.
  • Examination of signaling pathways involved in Nrf2 activation by polyphenols.

Main Results:

  • Flavonoids represent the largest category of phenolic Nrf2 activators, followed by nonflavonoids and phenolic acids.
  • Within subgroups, flavonols, flavones, and hydroxycinnamic acids are most prevalent; curcuminoids show the highest effective doses.
  • Polyphenols primarily activate Nrf2 via phosphorylation, frequently involving mitogen-activated protein kinases (MAPKs) and protein kinase B (Akt) pathways.

Conclusions:

  • Phenolic compounds, especially flavonoids, are significant Nrf2 activators with potential in treating hepatic disorders.
  • The primary mechanism involves Nrf2 phosphorylation, often modulated by MAPK and Akt signaling.
  • Current data are insufficient to establish definitive structure-activity relationships for phenolic Nrf2 activators.

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