The Benefits of the Citrus Flavonoid Diosmin on Human Retinal Pigment Epithelial Cells under High-Glucose Conditions.

Wayne Liu,Tang-Yao Hong,I-Min Liu,Shorong-Shii Liou

doi:10.3390/molecules22122251

Abstract

We investigate diosmin for its effect on the ARPE-19 human retinal pigment epithelial cells exposed to high glucose, a model of diabetic retinopathy (DR). After incubation for 4 days with a normal (5 mmol/L) concentration of D-glucose, ARPE-19 cells were exposed separately to normal or high concentrations of D-glucose (30 mmol/L) with or without diosmin at different concentrations (0.1, 1, 10 μg/mL) for another 48 h. Next, we assessed cell viability, reactive oxygen species (ROS) generation and antioxidant enzyme activities. In order to examine the underlying molecular mechanisms, we meanwhile analyzed the expressions of Bax, Bcl-2, total and phosphorylated JNK and p38 mitogen-activated protein kinase (MAPK). Diosmin dose dependently enhanced cell viability following high glucose treatment in ARPE-19 cells. The activities of superoxide dismutase and glutathione peroxidase, as well as the levels of reduced glutathione were decreased, while it was observed that levels of ROS in high glucose cultured ARPE-19 cells increased. High glucose also disturbed Bax and Bcl-2 expression, interrupted Bcl-2/Bax balance, and triggered subsequent cytochrome c release into the cytosol and activation of caspase-3. These detrimental effects were ameliorated dose dependently by diosmin. Furthermore, diosmin could abrogate high glucose-induced apoptosis as well as JNK and P38 MAPK phosphorylation in ARPE-19 cells. Our results suggest that treatment ARPE-19 cells with diosmin halts hyperglycemia-mediated oxidative damage and thus this compound may be a candidate for preventing the visual impairment caused by DR.

Highlights

Diabetic retinopathy (DR) is a prevalent retinal disease and a leading cause of blindness in diabetic patients worldwide
The protective effects of diosmin against high glucose-induced cell death in ARPE-19 cells were shown in Figure 1B, that diosmin recovered the cell death caused by high glucose in a dose-dependent manner and with almost 91.2% of the cells surviving at a dose of 10 μg/mL, whereas cell viability was about 30.2% without diosmin treatment
The results showed that the mean fluorescence of intracellular reactive oxygen species (ROS) production was increased by about 2.3 fold in high glucose cultured cells relative to normal-glucose vehicle-treated group (Figure 2)

Summary

Introduction

Diabetic retinopathy (DR) is a prevalent retinal disease and a leading cause of blindness in diabetic patients worldwide. The basis for the loss of vision associated with this disease has much to do with the oxidative damage inflicted on retinal pigment epithelial (RPE) cells by high glucose [1]. When reacting to injury or alterations in the hyperglycemic environment, RPE cells migrate and proliferate, leading to a breakdown in adhesion between the RPE and the choroidal capillaries. These pathological changes cause retinal vasopermeability increasing and the blood-retinal barrier breaking down, which in turn result in retinal hemorrhage, swelling, exudates, and retinal detachment [3].

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