(-)-Epicatechin attenuates high-glucose-induced inflammation by epigenetic modulation in human monocytes

Eur J Nutr. 2017 Apr;56(3):1369-1373. doi: 10.1007/s00394-015-1136-2. Epub 2015 Dec 24.

Abstract

Purpose: Diabetes is a pro-inflammatory state associated with increased monocyte activity. NF-κB is the master switch of inflammation and is activated during diabetes. (-)-Epicatechin (EC), the main cocoa flavonol, displays anti-inflammatory and anti-diabetic effects under high glucose conditions. Recently, it has been suggested that dietary polyphenols might modulate chromatin remodelling by epigenetic changes and regulate monocyte NF-κB activation and cytokine expression under diabetic conditions. The aim of the study was to test the potential anti-inflammatory role of EC via inducing posttranslational histone changes in the presence of a high glucose (HG) concentrations.

Methods: Human monocytic cells (THP-1 cells) were pre-treated with EC (5 μM) and 4 h later exposed to 25 mM glucose (HG) for a total of 24 h. Control cells were grown under normoglycemic conditions (NG, 5.5 mM glucose). Acetyl CBP/p300, HDAC4, total histone 3 (HH3), H3K9ac, H3K4me2 and H3K9me2, and phosphorylated and total levels of p65-NF-κB were analysed by Western blot. Histone acetyltransferase (HAT) activity was measured in nuclear lysates, and TNF-α release was evaluated in culture media.

Results: EC incubation restored to control levels (NG) the changes induced by HG in p-p65/p65-NF-ĸB ratio, acetyl CBP/p300 values and HAT activity. Moreover, EC pre-treatment counteracted the increased acetylation of H3K9 and H3K4 dimethylation and attenuated the diminished H3K9 dimethylation triggered by HG. EC also significantly decreased HG-enhanced HDAC4 levels and TNF-α release, respectively.

Conclusions: EC induces epigenetic changes and decreased NF-κB and TNF-α levels in human monocytes cultured in HG conditions such as in diabetes.

Keywords: Diabetes; Epicatechin; Epigenetics; Human monocytes THP-1 cells; Inflammation; Posttranslational histone modification.

MeSH terms

  • Acetylation
  • Anti-Inflammatory Agents / pharmacology*
  • Catechin / pharmacology*
  • Cell Line
  • Epigenesis, Genetic*
  • Gene Expression Regulation
  • Glucose / metabolism*
  • Histone Acetyltransferases / genetics
  • Histone Acetyltransferases / metabolism
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism
  • Histones / genetics
  • Histones / metabolism
  • Humans
  • Inflammation / drug therapy*
  • Monocytes / drug effects*
  • Monocytes / metabolism
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Histones
  • NF-kappa B
  • Repressor Proteins
  • Tumor Necrosis Factor-alpha
  • Catechin
  • Histone Acetyltransferases
  • HDAC4 protein, human
  • Histone Deacetylases
  • Glucose