Format

Send to

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

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

Author information

1
Department of Metabolism and Nutrition, Institute of Food Science and Technology and Nutrition (ICTAN), Consejo Superior de Investigaciones Científicas (CSIC), José Antonio Novais 10, Ciudad Universitaria, 28040, Madrid, Spain.
2
Department of Pathology & Immunology, Baylor College of Medicine and Texas Children's Hospital, 6621, Fannin Street, Houston, TX, 77030, USA.
3
Department of Pathology & Immunology, Baylor College of Medicine and Texas Children's Hospital, 6621, Fannin Street, Houston, TX, 77030, USA. devaraj@bcm.edu.

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

PMID:
26704714
DOI:
10.1007/s00394-015-1136-2
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center