Abstract
Age-related macular degeneration (AMD) is a degenerative disease of the retina where the molecular mechanism involves the production of vascular endothelial growth factor (VEGF), a factor of poor prognosis of the progression of the disease. Previous studies have shown that resveratrol, a polyphenol of grapevines, can prevent VEGF secretion induced by stress from retinal cells. Considering the fundamental role played by VEGF in development and progression of AMD, we investigate the potential effect of red wine extract (RWE) on VEGF secretion and its signaling pathway in human retinal cells ARPE-19. To examine the effect of RWE in ARPE-19, a quantitative and qualitative analysis of the RWE was performed by HPLC MS/MS. We show for the first time that RWE decreased VEGF-A secretion from ARPE-19 cells and its protein expression in concentration-dependent manner. RWE-induced alteration in VEGF-A production is associated with a down of VEGF-receptor 2 (VEGF-R2) protein expression and its phosphorylated intracytoplasmic domain. Subsequently, the activation of kinase pathway is disturbing and RWE prevents the phosphorylation of MEK and ERK 1/2 in human retinal cells ARPE-19. Finally, this study sheds light on the interest that the use of polyphenolic cocktails could represent in a prevention strategy.
Highlights
Since the last decade, several epidemiological studies have shown an inverse relation between the incidence of coronary diseases and wine consumption, compared to wine abstinence [1,2]
What about a more polyphenolic complex mixture such as red wine, which contains a wide variety of polyphenols? Considering the fundamental role played by vascular endothelial growth factor (VEGF) in development and progression of age-related macular degeneration (AMD), we investigated the potential effect of a red wine extract (RWE)
Red wine present a higher quantity of polyphenols estimated to be around 900–2500 mg/L in contrary to white wine composition estimated to be around 190–290 mg/L
Summary
Several epidemiological studies have shown an inverse relation between the incidence of coronary diseases and wine consumption, compared to wine abstinence [1,2]. In this context, we have previously shown in a controlled environment in hospital that a moderate consumption of red wine (250 mL/day), even for a short period (2 weeks), associated with a “Western prudent” diet, improves various blood parameters in the lipid and antioxidative status in patients with previous coronary ischemic accidents in comparison to patients receiving water [6]. We were able to demonstrate that a red wine extract (RWE) made it possible to act on inflammation by reducing the level of certain proinflammatory cytokines produced by immune cells [7] and by reducing the formation of an inflammatory complex in macrophages such as NLRP3 (NOD-like receptor family, pyrin domain containing 3) [8], or to reduce intestine polyp preneoplasia development in mice [9] These effects have been confirmed in other studies, where RWE can reduce tumoral C26 growth in BALB/c mice and vascular endothelial growth factor (VEGF) [10]. The latter factor is important for the neoangiogenesis, which is necessary for tumor growth and the spread of metastatic cells, but it is involved in other disease processes such as age-related macular degeneration (AMD)
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