Multiple regulations of Keap1/Nrf2 system by dietary phytochemicals

Mol Nutr Food Res. 2016 Aug;60(8):1731-55. doi: 10.1002/mnfr.201501017. Epub 2016 Jun 1.


Keap1/Nrf2 system plays a critical role on cellular protection by regulating many antioxidant and detoxification enzyme genes through the antioxidant response element (ARE). Thus, it must work constantly to prevent the accumulation of reactive oxygen species (ROS) because excess ROS are associated with many diseases such as cancer, cardiovascular complications, inflammation, and neurodegeneration. Dietary phytochemicals widely distributing in fruits and vegetables have been considered to possess cancer chemopreventive potential through the induction of Keap1/Nrf2 system-mediated antioxidant and detoxification enzymes in a variety of manners. The data are extensive and are not well classified on the molecular mechanisms. In this review, we first briefly introduce the current knowledge on Keap1/Nrf2 system regulation including Keap1-dependent and Keap1-independent cascades, and epigenetic pathway. Then, we summarize the molecular targets of Keap1/Nrf2 system by dietary phytochemicals, and finally review the crosstalk between Keap1/Nrf2 system and other cellular signaling pathways to regulate diverse chronic diseases by dietary phytochemicals. These comprehensive data will help us to understand the potential effects of dietary phytochemicals on the prevention of chronic diseases and maintenance of human health.

Keywords: Chemoprevention; Crosstalk; Keap1/Nrf2 system; Molecular targets; Phytochemical.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticarcinogenic Agents / pharmacology
  • Antioxidant Response Elements / drug effects
  • Antioxidants / pharmacology
  • Epigenomics
  • Humans
  • NF-E2-Related Factor 2 / physiology*
  • Neoplasms / prevention & control
  • Phytochemicals / pharmacology*
  • Reactive Oxygen Species / analysis
  • Signal Transduction / drug effects


  • Anticarcinogenic Agents
  • Antioxidants
  • NF-E2-Related Factor 2
  • Phytochemicals
  • Reactive Oxygen Species