Zerumbone, a Phytochemical of Subtropical Ginger, Protects against Hyperglycemia-Induced Retinal Damage in Experimental Diabetic Rats

Nutrients. 2016 Jul 25;8(8):449. doi: 10.3390/nu8080449.

Abstract

Diabetic retinopathy (DR), the most ordinary and specific microvascular complication of diabetes, is a disease of the retina. Zerumbone (ZER) is a monocyclic sesquiterpene compound, and based on reports, it is the predominant bioactive compound from the rhizomes of Zingiber zerumbet. The aim of the current study is to evaluate the protective effect of zerumbone against DR in streptozotocin (STZ)-induced diabetic rats. STZ-diabetic rats were treated with ZER (40 mg/kg) once a day orally for 8 weeks. ZER administration significantly (p < 0.05) lowered the levels of plasma glucose (32.5% ± 5.7% lower) and glycosylated hemoglobin (29.2% ± 3.4% lower) in STZ-diabetic rats. Retinal histopathological observations indicated that disarrangement and reduction in thickness of retinal layers were reversed in ZER-treated diabetic rats. ZER downregulated both the elevated levels of advanced glycosylated end products (AGEs) and the higher levels of the receptors for AGEs (RAGE) in retinas of diabetic rats. What's more, ZER significantly (p < 0.05) ameliorated diabetes-induced upregulation of tumor necrosis factor-α, interleukin (IL)-1 and IL-6. ZER also attenuated overexpression of vascular endothelial growth factor and intercellular adhesion molecule-1, and suppressed activation of nuclear factor (NF)-κB and apoptosis in the retinas of STZ-diabetic rats. Our results suggest ZER possesses retinal protective effects, which might be associated with the blockade of the AGEs/RAGE/NF-κB pathway and its anti-inflammatory activity.

Keywords: AGEs; NF-κB; diabetic retinopathy; zerumbone.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Cytokines / antagonists & inhibitors
  • Cytokines / blood
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / diet therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology
  • Diabetic Retinopathy / immunology
  • Diabetic Retinopathy / prevention & control*
  • Dietary Supplements*
  • Glycated Hemoglobin / analysis
  • Glycation End Products, Advanced / antagonists & inhibitors
  • Glycation End Products, Advanced / blood
  • Hyperglycemia / prevention & control
  • Hypoglycemic Agents / therapeutic use*
  • Intercellular Adhesion Molecule-1 / chemistry
  • Intercellular Adhesion Molecule-1 / metabolism
  • Male
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism
  • Random Allocation
  • Rats, Wistar
  • Receptor for Advanced Glycation End Products / agonists
  • Receptor for Advanced Glycation End Products / metabolism
  • Retina / immunology
  • Retina / metabolism
  • Retina / pathology
  • Rhizome / chemistry*
  • Sesquiterpenes / therapeutic use*
  • Vascular Endothelial Growth Factors / antagonists & inhibitors
  • Vascular Endothelial Growth Factors / metabolism
  • Zingiberaceae / chemistry*

Substances

  • Ager protein, rat
  • Anti-Inflammatory Agents, Non-Steroidal
  • Biomarkers
  • Cytokines
  • Glycated Hemoglobin A
  • Glycation End Products, Advanced
  • Hypoglycemic Agents
  • ICAM1 protein, rat
  • NF-kappa B
  • Receptor for Advanced Glycation End Products
  • Sesquiterpenes
  • Vascular Endothelial Growth Factors
  • Intercellular Adhesion Molecule-1
  • zerumbone