Dietary polyphenols mediated regulation of oxidative stress and chromatin remodeling in inflammation

Reactive oxygen species (ROS) alter nuclear histone acetylation and deacetylation (chromatin remodeling) leading to increased NF-κB-dependent gene expression of proinflammatory mediators. Naturally occurring dietary polyphenols such as curcumin (diferuloylmethane, an active component of spice turmeric) and resveratrol (phytoalexin, a flavanoid found in red wine) can directly scavenge ROS and modulate signaling pathways mediated via NF-κB and MAP kinase pathways, and upregulate glutathione biosynthesis gene via Nrf2 activation. They also downregulate expression of proinflammatory mediators, matrix metalloproteinases, adhesion molecules, and growth factor receptor genes by inhibiting histone acetyltransferase activity and activating histone deacetylase/sirtuins. Thus, these polyphenolic compounds have therapeutic value as antioxidant and anti-inflammatory therapy against chronic inflammatory epigenetically regulated diseases.Reactive oxygen species play a key role in enhancing the inflammation through sustained activation and phosphorylation of MAP kinases and redox-sensitive transcription factors, such as NF-κB and AP-1, in various inflammatory diseases.1 Oxidative stress also alters nuclear histone acetylation and deacetylation (chromatin remodeling) leading to increased gene expression of proinflammatory mediators.2,3 Recent studies from our laboratory show that oxidative stress enhances lung inflammation via expression of proinflammatory mediators through the activation of intrinsic histone acetyltransferase (HAT) activity of coactivator molecules.4–7 Increased histone acetylation was associated with increased activation of IκB kinase-α and interaction of NF-κB with CBP, leading to increased acetylation of RelA/p65 subunit of NF-κB. Oxidative stress also inhibits the activity of histone deacetylase (HDACs) (decreased HDAC2 levels), activates cells for NF-κB transactivation, and enhances inflammatory gene expression, which leads to chronic inflammatory response both in monocytes and epithelial cells in vitro, and in lungs in vivo.5–7 Oxidative stress also plays a role in poor efficacy of corticosteroids in various chronic inflammatory diseases.2,8 Thus, oxidative stress-mediated aberrant chromatin remodeling or histone modifications can lead to heightened …