Triggers for the Nrf2/ARE Signaling Pathway and Its Nutritional Regulation: Potential Therapeutic Applications of Ulcerative Colitis

Int J Mol Sci. 2021 Oct 22;22(21):11411. doi: 10.3390/ijms222111411.

Abstract

Ulcerative colitis (UC), which affects millions of people worldwide, is characterized by extensive colonic injury involving mucosal and submucosal layers of the colon. Nuclear factor E2-related factor 2 (Nrf2) plays a critical role in cellular protection against oxidant-induced stress. Antioxidant response element (ARE) is the binding site recognized by Nrf2 and leads to the expression of phase II detoxifying enzymes and antioxidant proteins. The Nrf2/ARE system is a key factor for preventing and resolving tissue injury and inflammation in disease conditions such as UC. Researchers have proposed that both Keap1-dependent and Keap1-independent cascades contribute positive effects on activation of the Nrf2/ARE pathway. In this review, we summarize the present knowledge on mechanisms controlling the activation process. We will further review nutritional compounds that can modulate activation of the Nrf2/ARE pathway and may be used as potential therapeutic application of UC. These comprehensive data will help us to better understand the Nrf2/ARE signaling pathway and promote its effective application in response to common diseases induced by oxidative stress and inflammation.

Keywords: Kelch-like ECH-associated protein 1; antioxidant response element; nuclear factor E2-related factor 2; nutritional regulation; ulcerative colitis.

Publication types

  • Review

MeSH terms

  • Animals
  • Antioxidant Response Elements / genetics
  • Antioxidant Response Elements / physiology*
  • Antioxidants / pharmacology
  • Colitis, Ulcerative / metabolism
  • Colitis, Ulcerative / therapy*
  • Cytoprotection / drug effects
  • Humans
  • Inflammation / metabolism
  • Kelch-Like ECH-Associated Protein 1 / metabolism
  • Kelch-Like ECH-Associated Protein 1 / physiology
  • NF-E2-Related Factor 2 / metabolism*
  • NF-E2-Related Factor 2 / physiology
  • Oxidants / pharmacology
  • Oxidative Stress / physiology
  • Signal Transduction / physiology

Substances

  • Antioxidants
  • KEAP1 protein, human
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Oxidants