Polyphenol-enriched cocoa protects the diabetic retina from glial reaction through the sirtuin pathway

J Nutr Biochem. 2015 Jan;26(1):64-74. doi: 10.1016/j.jnutbio.2014.09.003. Epub 2014 Oct 2.


Cocoa is rich in flavonoids, which are potent antioxidants with established benefits for cardiovascular health but unproven effects on neurodegeneration. Sirtuins (SIRTs), which make up a family of deacetylases, are thought to be sensitive to oxidation. In this study, the possible protective effects of cocoa in the diabetic retina were assessed. Rat Müller cells (rMCs) exposed to normal or high glucose (HG) or H2O2 were submitted to cocoa treatment in the presence or absence of SIRT-1 inhibitor and small interfering RNA The experimental animal study was conducted in streptozotocin-induced diabetic rats randomized to receive low-, intermediate-, or high-polyphenol cocoa treatments via daily gavage for 16 weeks (i.e., 0.12, 2.9 or 22.9 mg/kg/day of polyphenols). The rMCs exposed to HG or H2O2 exhibited increased glial fibrillary acidic protein (GFAP) and acetyl-RelA/p65 and decreased SIRT1 activity/expression. These effects were cancelled out by cocoa, which decreased reactive oxygen species production and PARP-1 activity, augmented the intracellular pool of NAD(+), and improved SIRT1 activity. The rat diabetic retinas displayed the early markers of retinopathy accompanied by markedly impaired electroretinogram. The presence of diabetes activated PARP-1 and lowered NAD(+) levels, resulting in SIRT1 impairment. This augmented acetyl RelA/p65 had the effect of up-regulated GFAP. Oral administration of polyphenol cocoa restored the above alterations in a dose-dependent manner. This study reveals that cocoa enriched with polyphenol improves the retinal SIRT-1 pathway, thereby protecting the retina from diabetic milieu insult.

Keywords: Cocoa; Diabetic retinopathy; GFAP; NAD(+); NF-kB; Neurodegeneration; SIRT1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Cacao / chemistry*
  • Catechin / blood
  • Chromatography, Liquid
  • Diabetes Mellitus, Experimental / etiology
  • Diabetes Mellitus, Experimental / prevention & control
  • Diabetic Retinopathy / prevention & control*
  • Dose-Response Relationship, Drug
  • Glial Fibrillary Acidic Protein / genetics
  • Glial Fibrillary Acidic Protein / metabolism*
  • Glucose / metabolism
  • Hydrogen Peroxide / metabolism
  • Male
  • Neuroglia / drug effects
  • Neuroglia / metabolism
  • Oxidative Stress / drug effects
  • Polyphenols / pharmacology*
  • Protective Agents / pharmacology*
  • Rats
  • Rats, Inbred SHR
  • Reactive Oxygen Species / metabolism
  • Retina / drug effects
  • Retina / metabolism
  • Signal Transduction
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism
  • Streptozocin / adverse effects
  • Tandem Mass Spectrometry
  • Transcription Factor RelA / genetics
  • Transcription Factor RelA / metabolism


  • Antioxidants
  • Glial Fibrillary Acidic Protein
  • Polyphenols
  • Protective Agents
  • Reactive Oxygen Species
  • Rela protein, rat
  • Transcription Factor RelA
  • Streptozocin
  • Catechin
  • Hydrogen Peroxide
  • Sirt1 protein, rat
  • Sirtuin 1
  • Glucose