Abstract
Blueberries possess abundant anthocyanins, which benefit eye health. The purpose of this study was to explore the protective functional role of blueberry anthocyanin extract (BAE) and its predominant constituents, malvidin (Mv), malvidin-3-glucoside (Mv-3-glc), and malvidin-3-galactoside (Mv-3-gal), on high glucose- (HG-) induced injury in human retinal capillary endothelial cells (HRCECs). The results showed that BAE, Mv, Mv-3-glc, and Mv-3-gal enhanced cell viability (P < 0.05 versus the HG group at 24 h); decreased the reactive oxygen species (ROS, P < 0.01 versus the HG group both at 24 and 48 h); and increased the enzyme activity of catalase (CAT) and superoxide dismutase (SOD) (P < 0.05 versus the HG group both at 24 and 48 h). Mv could greatly inhibit HG-induced Nox4 expression both at 24 and 48 h (P < 0.05), while BAE and Mv-3-gal downregulated Nox4 only at 48 h (P < 0.05). Mv, Mv-3-glc, and Mv-3-gal also changed nitric oxide (NO) levels (P < 0.05). BAE and Mv-3-glc also influenced angiogenesis by decreasing the vascular endothelial cell growth factor (VEGF) level and inhibiting Akt pathway (P < 0.05). Moreover, Mv and Mv-3-glc inhibited HG-induced intercellular adhesion molecule-1 (ICAM-1, P < 0.001) and nuclear factor-kappa B (NF-κB) (P < 0.05). It indicated that blueberry anthocyanins protected HRCECs via antioxidant and anti-inflammatory mechanisms, which could be promising molecules for the development of nutraceuticals to prevent diabetic retinopathy.
Highlights
Diabetic retinopathy (DR) is a common complication of diabetes mellitus and a leading cause of vision loss and blindness in diabetic patients [1]
We observed that stimulation with high glucose concentration (30 mmol/L, High glucose (HG): 64.03 ± 2.97%) for 24 h significantly decreased cell viability in comparison with normal glucose- (5.5 mmol/L, Normal glucose (NG): 100 ± 7.04%) incubated cells (P < 0 01)
Malvidin-3glucoside (Mv-3-glc: 91.16 ± 7.77%) was better than malvidin-3-galactoside (Mv-3-gal: 86.49 ± 3.32%). These indicated that high glucose inhibited cell growth, while blueberry anthocyanin extract (BAE), malvidin, and its glycosides protected the cell by inhibiting a decrease in cell viability caused by HG
Summary
Diabetic retinopathy (DR) is a common complication of diabetes mellitus and a leading cause of vision loss and blindness in diabetic patients [1]. Hyperglycemia is known to be the main contributing factor in the progression of the disease, which triggers pathological metabolic and biochemical changes that damage the retinal cells [2]. In the development of DR, retinal microvascular dysfunction includes the loss of endothelial cells and pericytes, capillary occlusion and bloodretinal barrier breakdown, and endothelial cell hypertrophy and degeneration that lead to capillary nonperfusion and hypoxia [3, 4]. Anthocyanins are known to have antioxidant, antimicrobial, antiviral, antiallergic, anticarcinogenic, anti-inflammatory, antimutagenic, and antiproliferative effects and may play an essential role in preventing various degenerative diseases including DR [6]. Anthocyanins from different vegetables and fruits, such as blueberry, bilberry, mulberry, maqui berry, blackcurrant, and black
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