Consumption of Polyphenol-Rich Zingiber Zerumbet Rhizome Extracts Protects against the Breakdown of the Blood-Retinal Barrier and Retinal Inflammation Induced by Diabetes.

Thing-Fong Tzeng,I-Min Liu,Shorong-Shii Liou,Tang-Yao Hong,Yu-Cheng Tzeng

doi:10.3390/nu7095369

Abstract

The present study investigates the amelioration of diabetic retinopathy (DR) by Zingiber zerumbet rhizome ethanol extracts (ZZRext) in streptozotocin-induced diabetic rats (STZ-diabetic rats). ZZRext contains high phenolic and flavonoid contents. STZ-diabetic rats were treated orally with ZZRext (200, 300 mg/kg per day) for three months. Blood-retinal barrier (BRB) breakdown and increased vascular permeability were found in diabetic rats, with downregulation of occludin, and claudin-5. ZZRext treatment effectively preserved the expression of occludin, and claudin-5, leading to less BRB breakdown and less vascular permeability. Retinal histopathological observation showed that the disarrangement and reduction in thickness of retinal layers were reversed in ZZRext-treated diabetic rats. Retinal gene expression of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, vascular endothelial growth factor, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were all decreased in ZZRext-treated diabetic rats. Moreover, ZZRext treatment not only inhibited the nuclear factor κB (NF-κB) activation, but also downregulated the protein expression of p38 mitogen-activated protein kinase (MAPK) in diabetic retina. In conclusion, the results suggest that the retinal protective effects of ZZRext occur through improved retinal structural change and inhibiting retinal inflammation. The antiretinopathy property of ZZRext might be related to the downregulation of p38 MAPK and NF-κB signal transduction induced by diabetes.

Highlights

The blood-retinal barrier (BRB) breakdown is the hallmark of many vascular diseases in the retina.The major component of this functional barrier has long been recognized to be at the level of the tight junctions between adjacent endothelial cells [1]
After three months of diabetes, the weight gain in STZ-diabetic rats was significantly less when compared with normal rats, and the blood glucose levels were significantly higher (Table 2)
Different to the effects of calcium dobesilate (CaD), our results suggest that the retinal protective effect of Zingiber zerumbet rhizome ethanol extracts (ZZRext) might be related to plasma glucose lowering pathway(s), and indicate that ZZRext has beneficial effects in attenuating the microvascular complications of diabetes, including diabetic retinopathy (DR)

Summary

Introduction

The major component of this functional barrier has long been recognized to be at the level of the tight junctions between adjacent endothelial cells [1]. Appropriate functioning of these junctional proteins in endothelial cells is essential for the maintenance of the normal function of the retina, and decreased expression of these proteins is known to cause various vascular pathologies, including diabetic retinopathy (DR), the most common and serious complication of diabetes mellitus (DM). The increased circulating levels of glucose accumulate in the retinal endothelial cells and result in the activation of various biochemical pathways. A number of signaling mechanisms, like nuclear factor kappa-B (NF-κB), mitogen-activated protein kinase (MAPK), intracellular adhesion molecules (ICAM)-1, and interleukin (IL)-1β, have been found to be implicated in the pathogenesis of DR [4]

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Results

Conclusion