Abstract

The present study examined effects of alpha-mangostin (α-MG) supplementation on the retinal microvasculature, including ocular blood flow (OBF) and blood-retinal barrier (BRB) permeability in a type 2 diabetic animal model. Male Sprague-Dawley rats were divided into four groups: normal control and diabetes with or without α-MG supplementation. Alpha-mangostin (200 mg/Kg/day) was administered by gavage feeding for 8 weeks. The effects of α-MG on biochemical and physiological parameters including mean arterial pressure (MAP), OBF, and BRB leakage were investigated. Additionally, levels of retinal malondialdehyde (MDA), advance glycation end products (AGEs), receptor of advance glycation end products (RAGE), tumour necrosis factor alpha (TNF-α), and vascular endothelial growth factor (VEGF) were evaluated. The elevated blood glucose, HbA1c, cholesterol, triglyceride, serum insulin, and HOMA-IR were observed in DM2 rats. Moreover, DM2 rats had significantly decreased OBF but statistically increased MAP and leakage of the BRB. The α-MG-treated DM2 rats showed significantly lower levels of retinal MDA, AGEs, RAGE, TNF-α, and VEGF than the untreated group. Interestingly, α-MG supplementation significantly increased OBF while it decreased MAP and leakage of BRB. In conclusion, α-MG supplementation could restore OBF and improve the BRB integrity, indicating its properties closely associated with antihyperglycemic, antioxidant, anti-inflammatory, and antiglycation activities.

Highlights

  • When the pancreas does not produce sufficient insulin or the body is unable to utilize the insulin, diabetes mellitus is developed

  • We investigated effects of αMG on diabetic retinopathy with reference to restoration of ocular blood flow (OBF) detected by a laser Doppler flowmetry [23] and an improvement of blood retinal barrier (BRB) integrity evaluated by the Evans blue dye techniques [24] in type 2 diabetic rats

  • Values are presented as mean ± standard error of mean (SEM). ns: not significantly different from the control group (CON) rats. +,++,+++indicate significant differences compared to the CON rats at P < 0.05, P < 0.01, and P < 0.001, respectively. #,##,###indicate significant differences compared to the DM2 rats at P < 0.05, P < 0.01, and P < 0.001, respectively

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Summary

Introduction

When the pancreas does not produce sufficient insulin or the body is unable to utilize the insulin, diabetes mellitus is developed. Long-lasting hyperglycemia leads to serious damage to organs and tissues of the body, including the vasculatures. The vascular complications of diabetes are associated with microvascular and macrovascular diseases which are retinopathy, nephropathy, cardiovascular disease, and cerebrovascular disease. Diabetic retinopathy (DR) is one of the most common microvascular complications of type 1 and type 2 diabetes leading to visual impairment and blindness [1, 2]. Several studies have reported that the origins of oxidative stress in diabetes are free radicals generated by several biochemical pathways. These pathways refer to polyol pathway [6], nonenzymatic glycation and advanced glycation end products (AGEs) [7], diacylglycerolprotein kinase C (DAG-PKC) [8], and hexosamine pathways [9]

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