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Age-related macular degeneration (AMD) is one of the most commonly occurring ocular diseases worldwide. This degenerative condition affects the retina and leads to the loss of central vision. The current treatments are focused on the late stage of the disease, but recent studies have highlighted the importance and benefits of preventive treatments and how good dietary habits can reduce the risk of progression to an advanced form of the disease. In this context, we studied whether resveratrol (RSV) or a polyphenolic cocktail, red wine extract (RWE), are able to prevent the initiating events of AMD (i.e., oxidative stress and inflammation) in human ARPE-19 retinal pigment epithelial (RPE) cells and macrophages. This study highlights that RWE and RSV can prevent hydrogen peroxide (H2O2) or 2,2′-Azobis(2-methylpropionamidine) dihydrochloride (AAPH)-induced oxidative stress and can subsequently prevent DNA damage via the inhibition of the ATM (ataxia telangiectasia-mutated)/Chk2 (checkpoint kinase 2) or Chk1 signaling pathways, respectively. Moreover, ELISA assays show that RWE and RSV can prevent the secretion of proinflammatory cytokines in RPE cells and in human macrophages. Interestingly, RWE exhibits a greater protective impact compared to RSV alone, even though RSV was more concentrated when used alone than in the red wine extract. Our results suggest that RWE and RSV may have potential interest as preventive nutritional supplementations against AMD. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is one of the most commonly occurring ocular diseases worldwide. This degenerative condition affects the retina and leads to the loss of central vision. The current treatments are focused on the late stage of the disease, but recent studies have highlighted the importance and benefits of preventive treatments and how good dietary habits can reduce the risk of progression to an advanced form of the disease. In this context, we studied whether resveratrol (RSV) or a polyphenolic cocktail, red wine extract (RWE), are able to prevent the initiating events of AMD (i.e., oxidative stress and inflammation) in human ARPE-19 retinal pigment epithelial (RPE) cells and macrophages. This study highlights that RWE and RSV can prevent hydrogen peroxide (H2O2) or 2,2′-Azobis(2-methylpropionamidine) dihydrochloride (AAPH)-induced oxidative stress and can subsequently prevent DNA damage via the inhibition of the ATM (ataxia telangiectasia-mutated)/Chk2 (checkpoint kinase 2) or Chk1 signaling pathways, respectively. Moreover, ELISA assays show that RWE and RSV can prevent the secretion of proinflammatory cytokines in RPE cells and in human macrophages. Interestingly, RWE exhibits a greater protective impact compared to RSV alone, even though RSV was more concentrated when used alone than in the red wine extract. Our results suggest that RWE and RSV may have potential interest as preventive nutritional supplementations against AMD.

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.

Red wine polyphenolic compounds have been demonstrated to possess antioxidant properties, and several studies have suggested that they might constitute a relevant dietary factor in the protection from coronary heart disease. The aim of the present study is to examine whether red wine extracts (RWE) can ameliorate oxysterol-induced endothelial response, and whether inhibition of adhesion molecule expression is involved in monocyte adhesion to endothelial cells. Surface expression and mRNA levels of adhesion molecules (intercellular adhesion molecule 1 and vascular cell adhesion molecule 1) were determined by ELISA and RT-PCR performed on human aortic endothelial cells (HAEC) monolayers stimulated with 7b-hydroxycholesterol or 25-hydroxycholesterol. Incubation of HAEC with oxysterols (10 muM) increased expression of adhesion molecules in a time-dependent manner. Pretreatment of HAEC with RWE at final concentrations of 1, 10, and 100 ng/ml significantly inhibited the increase of surface protein expression and mRNA levels. Adherence of monocytes to oxysterol-stimulated HAEC was increased compared to that of unstimulated cells. Treatment of HAEC with RWE significantly inhibited adherence of monocytes. These results suggest that RWE works as an anti-atherogenic agent through the inhibition of endothelial-dependent adhesive interactions with monocytes induced by oxysterols

The zebrafish embryo is a highly interesting biological model with applications in different scientific fields, such as biomedicine, pharmacology and toxicology. In this study, we used liquid chromatography/electrospray ionisation-linear ion trap quadrupole-Orbitrap-mass spectrometry (HPLC/ESI-LTQ-Orbitrap-MS) to identify the polyphenol compounds in a red wine extract and zebrafish embryos. Phenolic compounds and anthocyanin metabolites were determined in zebrafish embryos previously exposed to the red wine extract. Compounds were identified by injection in a high-resolution system (LTQ-Orbitrap) using accurate mass measurements in MS, MS 2 and MS 3 modes. To our knowledge, this research constitutes the first comprehensive identification of phenolic compounds in zebrafish by HPLC coupled to high-resolution mass spectrometry. [ABSTRACT FROM AUTHOR]

A reduction in the risk of coronary heart disease has been associated to moderate red wine consumption. We tested whether a nonalcoholic red wine extract would open mitochondrial KATP channels in guinea pig myocytes. The opening of mitochondrial KATP channels was assessed by endogenous flavoprotein fluorescence. Red wine extract (100 μg·mL-1) increased flavoprotein oxidation (10.9% ± 1.2%, n = 20). This effect was prevented by the mitochondrial KATP channel blocker, 5-hydroxydecanoate (500 µmol·L-1; 0.3% ± 1.1%, n = 13), confirming the hypothesis that red wine extract opens mitochondrial KATP channels. [ABSTRACT FROM AUTHOR]

The effects of a red wine extract supplement (Super S.O.D) on hypoxia/reoxygenation-induced apoptosis were examined in H9c2 cardiomyocytes. Super S.O.D pretreatment dose-dependently protected against hypoxia/reoxygenation-induced apoptosis in H9c2 cardiomyocytes. The cytoprotection was associated with increases in cellular reduced glutathione level and mitochondrial membrane potential, as well as the decrease in the extent of Ca2+-induced mitochondrial permeability transition (MPT) pore opening in both unchallenged and challenged cells, as compared with the unpretreated control. The results indicated that Super S.O.D pretreatment protected against hypoxia/reoxygenation-induced apoptosis in H9c2 cardiomyocytes, possibly mediated by the inhibition of MPT triggered by hypoxia/reoxygenation challenge. [ABSTRACT FROM AUTHOR]

Reperfusion of the previously ischemic myocardium causes a burst of reactive oxygen species production that eventually leads to tissue damage. In the present study, the effect of long-term treatment with a red wine extract-containing antioxidant supplement (Super S.O.D) on myocardial ischemia/reperfusion (I/R) injury was examined in rats. To investigate the biochemical mechanism( s) involved in the cardioprotection, the effects of Super S.O.D treatment on myocardial mitochondrial antioxidant and structural parameters were also investigated. Long-term treatment with Super S.O.D (0.55 and 1.10 g/kg/day x 15) caused a dose-dependent protection against myocardial I/R injury in rats, as evidenced by the significant decrease in the extent of lactate dehydrogenase leakage. The cardioprotection was associated with increases in reduced glutathione level and antioxidant enzyme activities, including glutathione reductase, glutathione S-transferases and Mn-superoxide dismutase, and decreases in the extents of malodialdehyde production, Ca2+ loading and cytochrome c release, in non-ischemic and ischemic-reperfused rat hearts. The results indicated that long-term Super S.O.D treatment enhanced myocardial mitochondrial antioxidant status and structural integrity, thereby protecting against I/R injury. [ABSTRACT FROM AUTHOR]

Abstract: The relationship between cholesterol and atherosclerosis has gained wide credence and red wine polyphenols have been shown to have an anti-atherogenic activity. In the present in vitro studies, we have evaluated and compared the effects of resveratrol, an active compound of red wine, and of a whole red wine polyphenolic extract (RWE) on the pancreatic bile salt-dependent lipase (BSDL). BSDL is involved in the duodenal hydrolysis of lipid esters and in part of cholesteryl esters thus favoring the bioavailability of free cholesterol. Resveratrol and RWE decrease the human and rat enzyme activities. Resveratrol and RWE also impaired the secretion of BSDL by the rat pancreatic AR4-2J cells used as secreting model. This effect is reversed by the removal of resveratrol or RWE from the cell culture medium. Further, resveratrol (but not RWE) affects the transcription of the gene encoding BSDL and dramatically diminishes the quantity of the enzyme that is expressed and secreted by AR4-2J cells. Results suggest that the hypolipemic effects of red wine polyphenols could partly originate from the inhibition of BSDL activity and secretion in the duodenum. In vivo, these effects could decrease the hydrolysis of dietary lipid esters and likely the absorption of free cholesterol. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effects of dietary supplementation with a nonalcoholic red wine extract (RWE), including resveratrol and polyphenols, on insulin sensitivity and Sirt1 expression in nondiabetic humans. The present study was a single-arm, open-label and prospective study. Twelve subjects received supplementation with RWE, including 19.2 mg resveratrol and 136 mg polyphenols, daily for 8 weeks. After 8 weeks, metabolic parameters, including glucose/lipid metabolism and inflammatory markers, were evaluated. mRNA expression of Sirt1 was evaluated in isolated peripheral blood mononuclear cells (PBMNCs). Additionally, Sirt1 and phosphorylated AMP-activated kinase (p-AMPK) expression were evaluated in cultured human monocytes (THP-1 cells). Supplementation with RWE for 8 weeks decreased the homeostasis model assessment for insulin resistance (HOMA-IR), which indicates an increase in insulin sensitivity. Serum low-density lipoprotein-cholesterol (LDL-C), triglyceride (TG) and interleukin-6 (IL-6) were significantly decreased by RWE supplementation for 8 weeks. Additionally, Sirt1 mRNA expression in isolated PBMNCs was significantly increased after 8 weeks of RWE supplementation. Moreover, the rate of increase in Sirt1 expression was positively correlated with the rate of change in HOMA-IR. The administration of RWE increased Sirt1 and p-AMPK expression in cultured THP-1 cells. Supplementation with RWE improved metabolism, such as insulin sensitivity, lipid profile and inflammation, in humans. Additionally, RWE supplementation induced an increase in Sirt1 expression in PBMNCs, which may be associated with an improvement in insulin sensitivity. [ABSTRACT FROM AUTHOR]

Scope: Scope: It is well established that immune response and inflammation promote tumoral progression. Immune cells communicate through direct contact or through cytokine secretion, and it is the pro-inflammatory status that will tip the balance toward tumor progression or anti-tumor immunity. It is demonstrated here that a red wine extract (RWE) can decrease inflammation through its action on the inflammasome complex. This study determines whether an RWE could impact other key actors of inflammation, including T helper 17 (Th17) immune cells in particular., Methods and Results: Methods and results: Using an RWE containing 4.16 g of polyphenols/liter of wine, it is shown that RWE decreases colorectal cancer cells in vitro and induces a reduction in colorectal tumor growth associated with a decrease in tumor-infiltrating lymphocytes in vivo. The process of T-lymphocyte differentiation in Th17 cells is altered by RWE, as revealed by the decrease in the expression of key actors controlling this process, such as signal transducer and activator of transcription 3 and retinoid acid-related orphan receptor γt. This disruption is associated with an inhibition of inflammatory interleukin 17 secretion., Conclusion: The data highlights the major involvement of Th17 immune cells in the biological effects of an RWE., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Gastrointestinal infections are considered a serious public health problem in view of their high incidence and the increasing antibiotic resistance of the microorganisms involved in their pathogenesis, namely Escherichia coli. Consequently, finding new ways to prevent and/or threat these infections is urgent. In this study we investigated whether a well-characterised polyphenolic red wine extract is able to inhibit the cytotoxic effects induced by a clinical pathogenic Escherichia coli strain (E. coli 270) against HT-29 colon epithelial cells. Firstly, we provide evidences showing that the E. coli strain triggered the death of the intestinal epithelial cells through the production and release of a toxin. Then we support that, in a concentration dependent way, RWE through both, a direct interaction with bacterial exotoxin and the epithelial cells, prevented the action of the toxin on the cells, significantly reducing cell death. This intends to constitute a position paper as detailed mechanisms for the inhibition of E. coli -induced toxicity by polyphenols are yet to be completely unraveled. However, considering that the amount of red wine polyphenols used can be easily achieved in a normal diet, this study suggests that RWE may provide a readily available dietary product with potential benefit for the prevention and/or treatment of intestinal infections induced by intestinal pathogenic bacteria and may open new therapeutic avenues for the development of potential natural antimicrobial agents. Image 1 • E. coli 270 causes the death of HT-29 colon epithelial cells. • The HT-29 cell death is caused by an exotoxin secreted by E. coli 270. • Red wine extract prevents the action of the E. coli -secreted exotoxin on the cells. • Red wine extract significantly inhibits the HT-29 cell death. [ABSTRACT FROM AUTHOR]