Consumption of polyphenol-rich Morus alba leaves extract attenuates early diabetic retinopathy: the underlying mechanism

Eur J Nutr. 2017 Jun;56(4):1671-1684. doi: 10.1007/s00394-016-1214-0. Epub 2016 Apr 8.

Abstract

Purpose: Beneficial effects of white mulberry against diabetes mellitus have been reported. However, the molecular mechanisms of how white mulberry can attenuate diabetic retinopathy remain poorly understood. Here, the mechanism underlying the protective effect of Morus alba leaves ethanolic extract on oxidative stress, inflammation, apoptosis, and angiogenesis in diabetic retinopathy was investigated.

Methods: Diabetes was induced by injection of streptozotocin. One week after, M. alba (100 mg/kg) was administrated to the rats daily for 16 weeks.

Results: Morus alba extract showed high content of polyphenolics and free radical scavenging activity. Oral M. alba administration significantly attenuated hyperglycemia and weight loss, and decreased sorbitol, fructose, protein kinase C, pro-inflammatory cytokines, and oxidative stress markers in retinas of the diabetic rats. Moreover, M. alba produced marked down-regulation of caspase-3 and Bax, with concomitant up-regulation of Bcl-2 in the diabetic retinas. M. alba also reduced the expression of VEGF in the retina.

Conclusion: These results indicate that M. alba has protective effect on diabetic retinopathy with possible mechanisms of inhibiting hyperglycemia-induced oxidative stress, apoptosis, inflammation, polyol pathway activation, and VEGF expression in the retina.

Keywords: Apoptosis; Diabetes; Mulberry; Oxidative stress; Retina.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Apoptosis / drug effects
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cytokines / genetics
  • Cytokines / metabolism
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / prevention & control
  • Diabetic Retinopathy / drug therapy*
  • Diabetic Retinopathy / prevention & control
  • Fructosamine / blood
  • Glycated Hemoglobin / metabolism
  • Hyperglycemia / prevention & control
  • Inflammation / drug therapy
  • Inflammation / prevention & control
  • Insulin / blood
  • Male
  • Morus / chemistry*
  • Oxidative Stress / drug effects
  • Phytochemicals / pharmacology
  • Plant Extracts / pharmacology*
  • Plant Leaves / chemistry*
  • Polyphenols / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Rats, Wistar
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antioxidants
  • Bax protein, rat
  • Bcl2 protein, rat
  • Cytokines
  • Glycated Hemoglobin A
  • Insulin
  • Phytochemicals
  • Plant Extracts
  • Polyphenols
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Fructosamine
  • Casp3 protein, rat
  • Caspase 3