The role of Nrf2 in the pathogenesis and treatment of ulcerative colitis

Abstract

Ulcerative colitis (UC) is a chronic inflammatory bowel disease involving mainly the colorectal mucosa and submucosa, the incidence of which has been on the rise in recent years. Nuclear factor erythroid 2-related factor 2 (Nrf2), known for its key function as a transcription factor, is pivotal in inducing antioxidant stress and regulating inflammatory responses. Numerous investigations have demonstrated the involvement of the Nrf2 pathway in maintaining the development and normal function of the intestine, the development of UC, and UC-related intestinal fibrosis and carcinogenesis; meanwhile, therapeutic agents targeting the Nrf2 pathway have been widely investigated. This paper reviews the research progress of the Nrf2 signaling pathway in UC.

Serotonin deficiency from constitutive SKN-1 activation drives pathogen apathy

“…Nuclear factor erythroid 2-related factor 2 (Nrf2), the human homologue of SKN-1, is known for its pivotal role in inducing antioxidant stress and regulating inflammatory responses. It plays a crucial role in the progression of intestinal fibrosis and carcinogenesis associated with inflammatory bowel diseases (IBD) [50]. The inflammatory response exhibited upon the onset of Ulcerative colitis (a form of IBD) leads to the dysregulation of the immune system, and constitutive activation of Nrf2 has been demonstrated to exacerbate cases of acute colitis to carcinoma [50, 51].…”

“…It plays a crucial role in the progression of intestinal fibrosis and carcinogenesis associated with inflammatory bowel diseases (IBD) [50]. The inflammatory response exhibited upon the onset of Ulcerative colitis (a form of IBD) leads to the dysregulation of the immune system, and constitutive activation of Nrf2 has been demonstrated to exacerbate cases of acute colitis to carcinoma [50, 51]. Serotonin synthesized mainly in the GI tract is involved in a vast array of biological processes revolving around the gut-brain axis.…”

Anti-oxidant and anti-inflammatory potential of different polymer-based mesalamine delayed-release granules in TNBS-induced ulcerative colitis in wistar rats

“…Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates antioxidants and inflammatory mechanisms. Under stress conditions, Nrf2 translocates to the nucleus and interacts with DNA to upregulate the transcription of antioxidant genes ( Peng et al, 2023 ). The cooperative communication between Nrf2 and NF- κ B helps in maintaining cellular homeostasis, attenuating immune response, and proteolytic enzyme activity ( e.g.…”

Epigenetic regulation and therapeutic strategies in ulcerative colitis

“…There have been various novel therapeutic approaches and drugs for the manipulation and treatment of UC, such as JAK inhibitors (tofacitinib, upadacitinib, filgotinib, TD-1473), phosphodiesterase inhibitors (apremilast), sphingosine receptor modulators (fingolimod, ozanimod and etrasimod), anti-adhesion molecules (natalizumab, vedolizumab, etrolizumab and ontamalimab) and anti-interleukin antibodies (ustekinumab targeting IL-12 and IL-23, mirikizumab targeting IL-23) ( Hirten and Sands, 2021 ). Besides, as an important transcription factor responsible for the control of cellular defense, Nrf2 regulates the progression of UC through multiple mechanisms, whose expression is also regulated by epigenetic modifications ( Peng et al, 2023 ). There have been many natural compounds and synthetic chemicals regulating the function of Nrf2 on UC, and novel drugs need to be developed to potentiate the defensive effects of Nrf2 ( Peng et al, 2023 ).…”

“…Besides, as an important transcription factor responsible for the control of cellular defense, Nrf2 regulates the progression of UC through multiple mechanisms, whose expression is also regulated by epigenetic modifications ( Peng et al, 2023 ). There have been many natural compounds and synthetic chemicals regulating the function of Nrf2 on UC, and novel drugs need to be developed to potentiate the defensive effects of Nrf2 ( Peng et al, 2023 ).…”