Dietary Polyphenols Remodel DNA Methylation Patterns of NRF2 in Chronic Disease

Abstract

The nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor crucial in regulating cellular homeostasis and apoptosis. The NRF2 gene has been implicated in various biological activities, including antioxidant, anti-inflammatory, and anticancer properties. NRF2 can be regulated genetically and epigenetically at the transcriptional, post-transcriptional, and translational levels. Although DNA methylation is one of the critical biological processes vital for gene expression, sometimes, anomalous methylation patterns result in the dysregulation of genes and consequent diseases and disorders. Several studies have reported promoter hypermethylation downregulated NRF2 expression and its downstream targets. In contrast to the unalterable nature of genetic patterns, epigenetic changes can be reversed, opening up new possibilities in developing therapies for various metabolic disorders and diseases. This review discusses the current state of the NRF2-mediated antioxidative and chemopreventive activities of several natural phytochemicals, including sulforaphane, resveratrol, curcumin, luteolin, corosolic acid, apigenin, and most other compounds that have been found to activate NRF2. This epigenetic reversal of hypermethylated NRF2 states provides new opportunities for research into dietary phytochemistry that affects the human epigenome and the possibility for cutting-edge approaches to target NRF2-mediated signaling to prevent chronic disorders.

Keywords

• hypomethylation
• hypermethylation
• epigenetics
• nuclear factor erythroid 2-related factor 2
• DNMTs
• dietary polyphenols