Effects of blueberry anthocyanins on retinal oxidative stress and inflammation in diabetes through Nrf2/HO-1 signaling

J Neuroimmunol. 2016 Dec 15;301:1-6. doi: 10.1016/j.jneuroim.2016.11.001. Epub 2016 Nov 9.


Anthocyanins, which are abundant in blueberries, provide significant protection against many chronic diseases. We investigated the effects of blueberry anthocyanins (BA) on diabetes-induced oxidative stress and inflammation in rat retinas. Male rats were divided randomly into five groups. Intraperitoneal injection of streptozotocin (STZ, 60mg/kg) was used to induce a rat diabetes model. BA at 20, 40, and 80mg/kg were given orally for about 12weeks. The results showed that BA could prevent diabetes-induced weight loss and increased blood glucose. BA also upregulated the antioxidant capacity of the retina, increased the content of glutathione (GSH) and glutathione peroxidase (GPx) activity, and decreased malondialdehyde (MDA) and reactive oxygen species (ROS) levels. Vascular endothelial growth factor (VEGF) and interleukin-1β (IL-1β) in the serum of diabetes model rats were upregulated, and BA reversed these changes significantly. Furthermore, BA increased the mRNA levels of Nrf2 and HO-1, as well as the nuclear location of Nrf2 and protein levels of HO-1. These results suggested that BA can protect retinal cells from diabetes-induced oxidative stress and inflammation, and this may be regulated through Nrf2/HO-1 signaling.

Keywords: Blueberry anthocyanins; Diabetic retinopathy; Inflammation; Nrf2/HO-1 signaling; Oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anthocyanins / pharmacology*
  • Anthocyanins / therapeutic use*
  • Blood Glucose / metabolism
  • Blueberry Plants / chemistry
  • Body Weight / drug effects
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / pathology*
  • Disease Models, Animal
  • GA-Binding Protein Transcription Factor / genetics
  • GA-Binding Protein Transcription Factor / metabolism
  • Glutathione / metabolism
  • Glutathione Peroxidase / metabolism
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism
  • Inflammation / etiology
  • Inflammation / prevention & control*
  • Interleukin-1beta / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Retina / drug effects*
  • Retina / metabolism
  • Signal Transduction / drug effects*


  • Anthocyanins
  • Blood Glucose
  • GA-Binding Protein Transcription Factor
  • Gabpa protein, rat
  • Interleukin-1beta
  • Malondialdehyde
  • Glutathione Peroxidase
  • Heme Oxygenase-1
  • Glutathione