The ethanol extract of Zingiber zerumbet rhizomes mitigates vascular lesions in the diabetic retina

Vascul Pharmacol. 2016 Jan:76:18-27. doi: 10.1016/j.vph.2015.08.015. Epub 2015 Aug 28.

Abstract

Diabetic retinopathy (DR) is a common diabetic eye disease which is well-known as the result of microvascular retinal changes. Although the ethanol extract from Zingiber zerumbet (L.) Smith rhizome (EEZZR) has been indicated to ameliorate hyperglycemia in diabetes, its protective effect on DR remains unclear. The aim of this study was to determine the effects of EEZZR on DR in streptozotocin (STZ) diabetic rats. Diabetic rats were treated orally with EEZZR (200, 300 mg/kg per day) or calcium dobesilate (CD; 500 mg/kg per day) for 12 weeks. EEZZR displayed similar characteristics to CD in reducing blood-retinal barrier permeability in diabetic rats. Retinal histopathological observation showed that retinal vessels were decreased in EEZZR-treated diabetic rats. EEZZR decreased the increased retinal expression of vascular endothelial growth factor (VEGF) and upregulate the expressions of renal pigment epithelium-derived factor (PEDF) in diabetic rats. Retinal mRNA expression of tumor necrosis factor-α, interleukin (IL)-1, IL-6, monocyte chemotactic proteins-1, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were all decreased in EEZZR-treated diabetic rats. Moreover, EEZZR could attenuate phosphorylation of nuclear factor Kappa B (NF-κB) p65 and extracellular signal-regulated kinase (ERK)1/2 as well as inhibit the nuclear translocation of pNF-κB p65 induced by diabetes. In conclusion, restoring the balance between stimulators and inhibitors of angiogenesis may be associated with the protective effect of EEZZR on DR. In addition, EEZZR can ameliorate retinal inflammation via transrepression of NF-κB and inhibition of ERK1/2 signaling pathway.

Keywords: Diabetic retinopathy; NF-κB; PEDF; VEGF; Zingiber zerumbet rhizomes.

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / diet therapy
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetic Retinopathy / drug therapy
  • Diabetic Retinopathy / metabolism
  • Ethanol / chemistry*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Eye Proteins / metabolism
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interleukin-1 / metabolism
  • Interleukin-6 / metabolism
  • MAP Kinase Signaling System / drug effects
  • Male
  • NF-kappa B / metabolism
  • Nerve Growth Factors / metabolism
  • Plant Extracts / pharmacology*
  • Rats
  • Rats, Wistar
  • Retina / drug effects*
  • Retina / metabolism
  • Retinal Vessels / drug effects*
  • Retinal Vessels / metabolism
  • Rhizome / chemistry*
  • Serpins / metabolism
  • Streptozocin / pharmacology
  • Tumor Necrosis Factor-alpha / metabolism
  • Vascular Cell Adhesion Molecule-1 / metabolism
  • Vascular Endothelial Growth Factor A / metabolism
  • Zingiberaceae / chemistry*

Substances

  • Eye Proteins
  • Interleukin-1
  • Interleukin-6
  • NF-kappa B
  • Nerve Growth Factors
  • Plant Extracts
  • Serpins
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Vascular Endothelial Growth Factor A
  • pigment epithelium-derived factor
  • Intercellular Adhesion Molecule-1
  • Ethanol
  • Streptozocin
  • Extracellular Signal-Regulated MAP Kinases