European Journal of Nutrition

, Volume 56, Issue 3, pp 1369–1373 | Cite as

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

  • Isabel Cordero-Herrera
  • Xinpu Chen
  • Sonia Ramos
  • Sridevi DevarajEmail author
Short Communication



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.


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.


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.


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


Diabetes Epicatechin Epigenetics Inflammation Human monocytes THP-1 cells Posttranslational histone modification 



I. Cordero-Herrera is a fellow of the FPI predoctoral program of MICINN.

Compliance with ethical standards

Conflict of interest

The authors declare that there are no conflicts of interest.


  1. 1.
    Yun J, Jialal I, Devaraj S (2009) Epigenetic regulation of high glucose-induced proinflammatory cytokine production in monocytes by curcumin. J Nutr Biochem 22:450–458CrossRefGoogle Scholar
  2. 2.
    Miao F, Gaw Gonzalo I, Lanting L, Natarajan R (2004) In vivo chromatin remodeling events leading to inflammatory gene transcription under diabetic conditions. J Biol Chem 279:18091–18097CrossRefGoogle Scholar
  3. 3.
    Wegner M, Neddermann D, Piorunska-Stolzmann M, Jagodzinski P (2014) Role of epigenetic mechanisms in the development of chronic complications of diabetes. Diabetes Res Clin Pract 105:164–175CrossRefGoogle Scholar
  4. 4.
    Reddy M, Zhang E, Natarajan R (2015) Epigenetic mechanisms in diabetic complications and metabolic memory. Diabetologia 58:443–455CrossRefGoogle Scholar
  5. 5.
    Miao F, Wu X, Zhang L, Yuan Y-C, Riggs A, Natarajan R (2007) Genome-wide analysis of histone lysine methylation variations caused by diabetic conditions in human monocytes. J Biol Chem 282:13854–13863CrossRefGoogle Scholar
  6. 6.
    Karlsen A, Paur I, Bøhn SK, Sakhi AK, Borge GI, Serafini M, Erlund I, Laake P, Tonstad S, Blomhoff R (2010) Bilberry juice modulates plasma concentration of NF-ĸB related inflammatory markers in subjects at increased risk of CVD. Eur J Nutr 49:345–355CrossRefGoogle Scholar
  7. 7.
    Vahid F, Zanda H, Nosrat-Mirshekarlou E, Najafi R, Hekmatdoost A (2015) The role dietary of bioactive compounds on the regulation of histone acetylases and deacetylases: a review. Gene 562:8–15CrossRefGoogle Scholar
  8. 8.
    Yun J, Jialal I, Devaraj S (2012) Effects of epigallocatechin gallate on regulatory T cell number and function in obese v. lean volunteers. Brit J Nutr 103:1771–1777CrossRefGoogle Scholar
  9. 9.
    Crescenti A, Sola R, Valls R, Caimari A, del Bas J, Anguera A, Angles N, Arola L (2013) Cocoa consumption alters the global DNA methylation of peripheral leukocytes in humans with cardiovascular disease risk factors: a randomized controlled trial. PLoS ONE 8:e65744CrossRefGoogle Scholar
  10. 10.
    Kawahara TLA, Michishita E, Adler AS, Damian M, Berber E, Lin M, McCord RA, Ongaigui KCL, Boxer LD, Chang HY, Chua KF (2009) SIRT6 links histone H3 lysine 9 deacetylation to control of NF-κB dependent gene expression and organismal lifespan. Cell 136(1):62–74CrossRefGoogle Scholar
  11. 11.
    Wang X, Liu J, Zhen J, Zhang C, Wan Q, Liu G, Wei X, Zhang Y, Wang Z, Han H, Xu H, Bao C, Song Z, Zhang X, Li N, Yi F (2014) Histone deacetylase 4 selectively contributes to podocyte injury in diabetic nephropathy. Kideny Int 86:712–725CrossRefGoogle Scholar
  12. 12.
    Holt RR, Lazarus SA, Sullards MC, Zhu QY, Schramm DD, Hammerstone JF, Fraga CG, Schmitz HH, Keen CL (2002) Procyanidin dimer B2 [epicatechin-(4-beta-8)- epicatechin] in human plasma after the consumption of a flavanol-rich cocoa. Am J Clin Nutr 76:798–804Google Scholar
  13. 13.
    Kroon PA, Clifford MN, Crozier A, Day AJ, Donovan JL, Manach C, Williamson G (2004) How should we assess the effects of exposure to dietary polyphenols in vitro? Am J Clin Nutr 80:15–21Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Isabel Cordero-Herrera
    • 1
  • Xinpu Chen
    • 2
  • Sonia Ramos
    • 1
  • Sridevi Devaraj
    • 2
    Email author
  1. 1.Department of Metabolism and Nutrition, Institute of Food Science and Technology and Nutrition (ICTAN)Consejo Superior de Investigaciones Científicas (CSIC)MadridSpain
  2. 2.Department of Pathology & ImmunologyBaylor College of Medicine and Texas Children’s HospitalHoustonUSA

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