Targeting Nrf2 signaling pathway by quercetin in the prevention and treatment of neurological disorders: An overview and update on new developments

Fundam Clin Pharmacol. 2023 Dec;37(6):1050-1064. doi: 10.1111/fcp.12926. Epub 2023 Jun 16.

Abstract

Background: Neurological disorders (NLDs) are widely acknowledged as a significant public health concern worldwide. Stroke, Alzheimer's disease (AD), and traumatic brain injury (TBI) are three of these disorders that have sparked major study attention. Neurological dysfunction, protein buildup, oxidation and neuronal injury, and aberrant mitochondria are all prevalent neuropathological hallmarks of these disorders. The signaling cascade of nuclear factor erythroid 2 related factor 2 (Nrf2) shares all of them as a common target. Several studies have found that overexpression of Nrf2 is a promising treatment method in NLDs. Effective treatment of these disorders continues to be a universal concern regardless of various medicines. In order to treat a variety of neurological problems, organic remedies may provide an alternative treatment. It has been demonstrated that polyphenols like quercetin (Que) offer considerable capabilities for treating NLDs. One of Que's greatest key targets, Nrf2, has the capacity to control the production of a number of cytoprotective enzymes that exhibit neuroprotective, detoxifying, and antioxidative effects. Additionally, Que enhanced the expression of Nrf2 and inhibited alterations in the shape and death of neurons in the hippocampus.

Objective: In this review, we have focused on Que's medicinal prospects as a neuroprotective drug.

Methods: PubMed, Scopus, Science Direct, and Google Scholar were used to search articles for this study.

Results: The findings of this research demonstrate that (1) Que protected the blood-brain barrier via stimulating Nrf2 in animal stroke, which alleviated ischemic reperfusion and motor dysfunction. (2) By triggering the Nrf2 pathway, Que reduced the neuroinflammation and oxidative damage brought on by TBI in the cortex. (3) In an experimental model of AD, Que enhanced cognitive function by decreasing A1-4, antioxidant activity, and Nrf2 levels in the brain.

Conclusion: We discuss recent research on Que-mediated Nrf2 expression in the management of several NLDs in this paper.

Keywords: Nrf2; neurological disorders; neuroprotective; oxidative stress; quercetin.

Publication types

  • Review

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Brain Injuries, Traumatic* / drug therapy
  • NF-E2-Related Factor 2 / metabolism
  • Nervous System Diseases* / drug therapy
  • Neuroprotective Agents* / pharmacology
  • Neuroprotective Agents* / therapeutic use
  • Oxidative Stress
  • Quercetin / pharmacology
  • Quercetin / therapeutic use
  • Signal Transduction
  • Stroke* / drug therapy

Substances

  • Quercetin
  • NF-E2-Related Factor 2
  • Antioxidants
  • Neuroprotective Agents