Nutrients

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Open AccessArticle

Acute Resveratrol Consumption Improves Neurovascular Coupling Capacity in Adults with Type 2 Diabetes Mellitus

by Rachel H.X. Wong, Daniel Raederstorff and Peter R.C. Howe

Nutrients 2016, 8(7), 425; https://doi.org/10.3390/nu8070425 - 12 Jul 2016

Cited by 77 | Viewed by 8178

Abstract

Background: Poor cerebral perfusion may contribute to cognitive impairment in type 2 diabetes mellitus (T2DM). We conducted a randomized controlled trial to test the hypothesis that resveratrol can enhance cerebral vasodilator function and thereby alleviate the cognitive deficits in T2DM. We have already [...] Read more.

Background: Poor cerebral perfusion may contribute to cognitive impairment in type 2 diabetes mellitus (T2DM). We conducted a randomized controlled trial to test the hypothesis that resveratrol can enhance cerebral vasodilator function and thereby alleviate the cognitive deficits in T2DM. We have already reported that acute resveratrol consumption improved cerebrovascular responsiveness (CVR) to hypercapnia. We now report the effects of resveratrol on neurovascular coupling capacity (CVR to cognitive stimuli), cognitive performance and correlations with plasma resveratrol concentrations. Methods: Thirty-six T2DM adults aged 40–80 years were randomized to consume single doses of resveratrol (0, 75, 150 and 300 mg) at weekly intervals. Transcranial Doppler ultrasound was used to monitor changes in blood flow velocity (BFV) during a cognitive test battery. The battery consisted of dual-tasking (finger tapping with both Trail Making task and Serial Subtraction 3 task) and a computerized multi-tasking test that required attending to four tasks simultaneously. CVR to cognitive tasks was calculated as the per cent increase in BFV from pre-test basal to peak mean blood flow velocity and also as the area under the curve for BFV. Results: Compared to placebo, 75 mg resveratrol significantly improved neurovascular coupling capacity, which correlated with plasma total resveratrol levels. Enhanced performance on the multi-tasking test battery was also evident following 75 mg and 300 mg of resveratrol. Conclusion: a single 75 mg dose of resveratrol was able to improve neurovascular coupling and cognitive performance in T2DM. Evaluation of benefits of chronic resveratrol supplementation is now warranted. Full article

(This article belongs to the Special Issue Selected Papers from Resveratrol Regional Meeting 2015)

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2639 KiB

Open AccessArticle

Piceatannol and Other Wine Stilbenes: A Pool of Inhibitors against α-Synuclein Aggregation and Cytotoxicity

by Hamza Temsamani, Stéphanie Krisa, Marion Decossas-Mendoza, Olivier Lambert, Jean-Michel Mérillon and Tristan Richard

Nutrients 2016, 8(6), 367; https://doi.org/10.3390/nu8060367 - 15 Jun 2016

Cited by 28 | Viewed by 7097

Abstract

The aggregation of α-synuclein is one on the key pathogenic events in Parkinson’s disease. In the present study, we investigated the inhibitory capacities of stilbenes against α-synuclein aggregation and toxicity. Thioflavin T fluorescence, transmission electronic microscopy, and SDS-PAGE analysis were performed to investigate [...] Read more.

The aggregation of α-synuclein is one on the key pathogenic events in Parkinson’s disease. In the present study, we investigated the inhibitory capacities of stilbenes against α-synuclein aggregation and toxicity. Thioflavin T fluorescence, transmission electronic microscopy, and SDS-PAGE analysis were performed to investigate the inhibitory effects of three stilbenes against α-synuclein aggregation: piceatannol, ampelopsin A, and isohopeaphenol. Lipid vesicle permeabilization assays were performed to screen stilbenes for protection against membrane damage induced by aggregated α-synuclein. The viability of PC12 cells was examined using an MTT assay to assess the preventive effects of stilbenes against α-synuclein-induced toxicity. Piceatannol inhibited the formation of α synuclein fibrils and was able to destabilize preformed filaments. It seems to induce the formation of small soluble complexes protecting membranes against α-synuclein-induced damage. Finally, piceatannol protected cells against α-synuclein-induced toxicity. The oligomers tested (ampelopsin A and hopeaphenol) were less active. Full article

(This article belongs to the Special Issue Selected Papers from Resveratrol Regional Meeting 2015)

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5300 KiB

Open AccessArticle

Nutraceutical with Resveratrol and Omega-3 Fatty Acids Induces Autophagy in ARPE-19 Cells

by Ali Koskela, Mika Reinisalo, Goran Petrovski, Debasish Sinha, Céline Olmiere, Reijo Karjalainen and Kai Kaarniranta

Nutrients 2016, 8(5), 284; https://doi.org/10.3390/nu8050284 - 11 May 2016

Cited by 37 | Viewed by 9458

Abstract

Impaired autophagic and proteasomal cleansing have been documented in aged retinal pigment epithelial (RPE) cells and age-related macular degeneration (AMD). Omega-3 fatty acids and resveratrol have many positive homeostatic effects in RPE cells. In this work, ARPE-19 cells were treated with 288 ng [...] Read more.

Impaired autophagic and proteasomal cleansing have been documented in aged retinal pigment epithelial (RPE) cells and age-related macular degeneration (AMD). Omega-3 fatty acids and resveratrol have many positive homeostatic effects in RPE cells. In this work, ARPE-19 cells were treated with 288 ng of Resvega, containing 30 mg of trans resveratrol and 665 mg of omega-3 fatty acids, among other nutrients, with proteasome inhibitor MG-132 or autophagy inhibitor bafilomycin A1 up to 48 h. Autophagy markers p62/SQSTM1 (p62) and LC3 (microtubule-associated protein 1A/1B-light chain 3) were analyzed by Western blotting. Fluorescence microscopy with mCherry-GFP-LC3 plasmid was applied to study the autophagy flux, and cytoprotective effects were investigated with colorimetric MTT and LDH assays. Resvega induced autophagy by showing increased autolysosome formation and autophagy flux, and the change in the p62 and LC3 protein levels further confirmed the fluorescent microscopy results. Moreover, Resvega provided a clear cytoprotection under proteasome inhibition. These findings highlight the potential of the nutraceuticals containing resveratrol, omega-3 fatty acids and other nutrients in the prevention of ARPE-19 cell damage. Full article

(This article belongs to the Special Issue Selected Papers from Resveratrol Regional Meeting 2015)

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2224 KiB

Open AccessArticle

Resveratrol Interferes with IL1-β-Induced Pro-Inflammatory Paracrine Interaction between Primary Chondrocytes and Macrophages

by Emeric Limagne, Allan Lançon, Dominique Delmas, Mustapha Cherkaoui-Malki and Norbert Latruffe

Nutrients 2016, 8(5), 280; https://doi.org/10.3390/nu8050280 - 11 May 2016

Cited by 57 | Viewed by 6704

Abstract

State of the art. Osteoarthritis (OA) is a chronic articular disease characterized by cartilage degradation and osteophyte formation. OA physiopathology is multifactorial and involves mechanical and hereditary factors. So far, there is neither preventive medicine to delay cartilage breakdown nor curative treatment. [...] Read more.

State of the art. Osteoarthritis (OA) is a chronic articular disease characterized by cartilage degradation and osteophyte formation. OA physiopathology is multifactorial and involves mechanical and hereditary factors. So far, there is neither preventive medicine to delay cartilage breakdown nor curative treatment. Objectives. To investigate pro-inflammatory paracrine interactions between human primary chondrocytes and macrophages following interleukin-1-β (IL-1β) treatment; to evaluate the molecular mechanism responsible for the inhibitory effect of resveratrol. Results. The activation of NF-κB in chondrocytes by IL-1β induced IL-6 secretion. The latter will then activate STAT3 protein in macrophages. Moreover, STAT3 was able to positively regulate IL-6 secretion, as confirmed by the doubling level of IL-6 in the coculture compared to macrophage monoculture. These experiments confirm the usefulness of the coculture model in the inflammatory arthritis-linked process as a closer biological situation to the synovial joint than separated chondrocytes and macrophages. Il also demonstrated the presence of an inflammatory amplification loop induced by IL-1β. Resveratrol showed a strong inhibitory effect on the pro-inflammatory marker secretion. The decrease of IL-6 secretion is dependent on the NFκB inhibition in the chondrocytes. Such reduction of the IL-6 level can limit STAT3 activation in the macrophages, leading to the interruption of the inflammatory amplification loop. Conclusion. These results increase our understanding of the anti-inflammatory actions of resveratrol and open new potential approaches to prevent and treat osteoarthritis. Full article

(This article belongs to the Special Issue Selected Papers from Resveratrol Regional Meeting 2015)

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412 KiB

Open AccessArticle

Clinical Evaluation of Effects of Chronic Resveratrol Supplementation on Cerebrovascular Function, Cognition, Mood, Physical Function and General Well-Being in Postmenopausal Women—Rationale and Study Design

by Hamish Michael Evans, Peter Ranald Charles Howe and Rachel Heloise Xiwen Wong

Nutrients 2016, 8(3), 150; https://doi.org/10.3390/nu8030150 - 9 Mar 2016

Cited by 34 | Viewed by 8867

Abstract

Background: This methodological paper presents both a scientific rationale and a methodological approach for investigating the effects of resveratrol supplementation on mood and cognitive performance in postmenopausal women. Postmenopausal women have an increased risk of cognitive decline and dementia, which may be at [...] Read more.

Background: This methodological paper presents both a scientific rationale and a methodological approach for investigating the effects of resveratrol supplementation on mood and cognitive performance in postmenopausal women. Postmenopausal women have an increased risk of cognitive decline and dementia, which may be at least partly due to loss of beneficial effects of estrogen on the cerebrovasculature. We hypothesise that resveratrol, a phytoestrogen, may counteract this risk by enhancing cerebrovascular function and improving regional blood flow in response to cognitive demands. A clinical trial was designed to test this hypothesis. Method: Healthy postmenopausal women were recruited to participate in a randomised, double-blind, placebo-controlled (parallel comparison) dietary intervention trial to evaluate the effects of resveratrol supplementation (75 mg twice daily) on cognition, cerebrovascular responsiveness to cognitive tasks and overall well-being. They performed the following tests at baseline and after 14 weeks of supplementation: Rey Auditory Verbal Learning Test, Cambridge Semantic Memory Battery, the Double Span and the Trail Making Task. Cerebrovascular function was assessed simultaneously by monitoring blood flow velocity in the middle cerebral arteries using transcranial Doppler ultrasound. Conclusion: This trial provides a model approach to demonstrate that, by optimising circulatory function in the brain, resveratrol and other vasoactive nutrients may enhance mood and cognition and ameliorate the risk of developing dementia in postmenopausal women and other at-risk populations. Full article

(This article belongs to the Special Issue Selected Papers from Resveratrol Regional Meeting 2015)

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2656 KiB

Open AccessArticle

Sirt1 Is Required for Resveratrol-Mediated Chemopreventive Effects in Colorectal Cancer Cells

by Constanze Buhrmann, Parviz Shayan, Bastian Popper, Ajay Goel and Mehdi Shakibaei

Nutrients 2016, 8(3), 145; https://doi.org/10.3390/nu8030145 - 5 Mar 2016

Cited by 103 | Viewed by 10938

Abstract

Sirt1 is a NAD⁺-dependent protein-modifying enzyme involved in regulating gene expression, DNA damage repair, metabolism and survival, as well as acts as an important subcellular target of resveratrol. The complex mechanisms underlying Sirt1 signaling during carcinogenesis remain controversial, as it can [...] Read more.

Sirt1 is a NAD⁺-dependent protein-modifying enzyme involved in regulating gene expression, DNA damage repair, metabolism and survival, as well as acts as an important subcellular target of resveratrol. The complex mechanisms underlying Sirt1 signaling during carcinogenesis remain controversial, as it can serve both as a tumor promoter and suppressor. Whether resveratrol-mediated chemopreventive effects are mediated via Sirt1 in CRC growth and metastasis remains unclear; which was the subject of this study. We found that resveratrol suppressed proliferation and invasion of two different human CRC cells in a dose-dependent manner, and interestingly, this was accompanied with a significant decrease in Ki-67 expression. By transient transfection of CRC cells with Sirt1-ASO, we demonstrated that the anti-tumor effects of resveratrol on cells was abolished, suggesting the essential role of this enzyme in the resveratrol signaling pathway. Moreover, resveratrol downregulated nuclear localization of NF-κB, NF-κB phosphorylation and its acetylation, causing attenuation of NF-κB-regulated gene products (MMP-9, CXCR4) involved in tumor-invasion and metastasis. Finally, Sirt1 was found to interact directly with NF-κB, and resveratrol did not suppress Sirt1-ASO-induced NF-κB phosphorylation, acetylation and NF-κB-regulated gene products. Overall, our results demonstrate that resveratrol can suppress tumorigenesis, at least in part by targeting Sirt1 and suppression of NF-κB activation. Full article

(This article belongs to the Special Issue Selected Papers from Resveratrol Regional Meeting 2015)

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1496 KiB

Open AccessArticle

Nanoscale Delivery of Resveratrol towards Enhancement of Supplements and Nutraceuticals

by Ana Rute Neves, Susana Martins, Marcela A. Segundo and Salette Reis

Nutrients 2016, 8(3), 131; https://doi.org/10.3390/nu8030131 - 2 Mar 2016

Cited by 76 | Viewed by 8831

Abstract

Resveratrol was investigated in terms of its stability, biocompatibility and intestinal permeability across Caco-2 cell monolayers in its free form or encapsulated in solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs). SLNs and NLCs presented a mean diameter between 160 and 190 [...] Read more.

Resveratrol was investigated in terms of its stability, biocompatibility and intestinal permeability across Caco-2 cell monolayers in its free form or encapsulated in solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs). SLNs and NLCs presented a mean diameter between 160 and 190 nm, high negative zeta potential of −30 mV and resveratrol entrapment efficiency of 80%, suggesting they are suitable for resveratrol oral delivery. Nanoencapsulation effectively protected resveratrol from photodegradation, and MTT assays demonstrated that neither resveratrol nor lipid nanoparticles adversely affected cell viability and integrity of Caco-2 cell monolayers. The in vitro intestinal permeability of resveratrol was significantly increased by NLCs, and SLNs did not impair the absorption of resveratrol. Resveratrol oral absorption can be enhanced during meals, since the intestinal permeability was increased in the presence of fed-state intestinal juices. SLNs and NLCs constitute carrier systems for resveratrol oral administration, for further use as supplements or nutraceuticals. Full article

(This article belongs to the Special Issue Selected Papers from Resveratrol Regional Meeting 2015)

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406 KiB

Open AccessArticle

Resveratrol Supplementation in Schizophrenia Patients: A Randomized Clinical Trial Evaluating Serum Glucose and Cardiovascular Risk Factors

by Karine Zortea, Viviane C. Franco, Lenise P. Francesconi, Keila M. M. Cereser, Maria Inês R. Lobato and Paulo S. Belmonte-de-Abreu

Nutrients 2016, 8(2), 73; https://doi.org/10.3390/nu8020073 - 29 Jan 2016

Cited by 46 | Viewed by 6900

Abstract

Background: Patients with schizophrenia (SZ) are generally overweight or obese and have several metabolic disorders. Additionally, such patients have a lower life expectancy and the main cause of their increased mortality is cardiovascular disease (CVD). The objective of this study was to determine [...] Read more.

Background: Patients with schizophrenia (SZ) are generally overweight or obese and have several metabolic disorders. Additionally, such patients have a lower life expectancy and the main cause of their increased mortality is cardiovascular disease (CVD). The objective of this study was to determine the efficacy of resveratrol supplementation on serum glucose and CVD risk factors in individuals with SZ. Methods and Results: This is a four-week randomized, double-blind controlled trial (registration No.: NCT 02062190) in which 19 men with a diagnosis of SZ, aged 18 to 65, were assigned to either a resveratrol supplement group (200 mg/day) or a placebo group (200 mg/day). In short, we did not observe significant changes after resveratrol supplementation. In the placebo group, we found a significant increase in total cholesterol levels (p = 0.024) and in LDL-cholesterol (p = 0.002), as well as a decrease in body fat percentage (p = 0.038). The placebo group also showed an increase in triglycerides (9.19%) and a reduction in HDL-cholesterol (4.88%). In the resveratrol group, triglycerides decreased (7.64%). Conclusion: In summary, oral resveratrol in reasonably low dosages (200 mg daily) brought no differences to body weight, waist circumference, glucose, and total cholesterol. It was possible to note that the lipid profile in the placebo group worsened and, although no significant differences were found, we can assume that resveratrol might prevent lipid profile damage and that the intervention affected the lipoprotein metabolism at various levels. Full article

(This article belongs to the Special Issue Selected Papers from Resveratrol Regional Meeting 2015)

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Review

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Open AccessFeature PaperReview

Challenges in Analyzing the Biological Effects of Resveratrol

by Cihan Suleyman Erdogan and Ole Vang

Nutrients 2016, 8(6), 353; https://doi.org/10.3390/nu8060353 - 9 Jun 2016

Cited by 39 | Viewed by 8919

Abstract

The suggested health effects (e.g., disease prevention) of dietary bioactive compounds such as resveratrol are challenging to prove in comparison to man-made drugs developed for therapeutic purposes. Dietary bioactive compounds have multiple cellular targets and therefore have a variety of biological effects. Extrapolating [...] Read more.

The suggested health effects (e.g., disease prevention) of dietary bioactive compounds such as resveratrol are challenging to prove in comparison to man-made drugs developed for therapeutic purposes. Dietary bioactive compounds have multiple cellular targets and therefore have a variety of biological effects. Extrapolating the biological effects of dietary compounds from in vitro and in vivo animal experiments to humans may lead to over- or under-estimation of the effect and role of these compounds. The present paper will discuss a few of these challenges and suggest directions for future research. Questions we address include: (1) Is the combinatorial effect of resveratrol and other compounds real? (2) What are the real and relevant doses of resveratrol after administration? and (3) Is it possible to estimate the preventive effect of resveratrol by clinical trials using standard experimental designs? The examples concerning resveratrol taken from the scientific literature are mainly from 2010 and later. The challenges pointed out in this review are similar to most naturally occurring bioactive compounds. Full article

(This article belongs to the Special Issue Selected Papers from Resveratrol Regional Meeting 2015)

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Open AccessReview

Resveratrol and Cardiovascular Diseases

by Dominique Bonnefont-Rousselot

Nutrients 2016, 8(5), 250; https://doi.org/10.3390/nu8050250 - 2 May 2016

Cited by 338 | Viewed by 31988

Abstract

The increased incidence of cardiovascular diseases (CVDs) has stimulated research for substances that could improve cardiovascular health. Among them, resveratrol (RES), a polyphenolic compound notably present in grapes and red wine, has been involved in the “French paradox”. RES is known for its [...] Read more.

The increased incidence of cardiovascular diseases (CVDs) has stimulated research for substances that could improve cardiovascular health. Among them, resveratrol (RES), a polyphenolic compound notably present in grapes and red wine, has been involved in the “French paradox”. RES is known for its antioxidant and anti-inflammatory properties and for its ability to upregulate endothelial NO synthase (eNOS). RES was able to scavenge ^•OH/O₂^•− and peroxyl radicals, which can limit the lipid peroxidation processes. Moreover, in bovine aortic endothelial cells (BAEC) under glucose-induced oxidative stress, RES restored the activity of dimethylargininedimethylaminohydrolase (DDAH), an enzyme that degrades an endogenous inhibitor of eNOS named asymmetric dimethylarginine (ADMA). Thus, RES could improve ^•NO availability and decrease the endothelial dysfunction observed in diabetes. Preclinical studies have made it possible to identify molecular targets (SIRT-1, AMPK, Nrf2, NFκB…); however, there are limited human clinical trials, and difficulties in the interpretation of results arise from the use of high-dose RES supplements in research studies, whereas low RES concentrations are present in red wine. The discussions on potential beneficial effects of RES in CVDs (atherosclerosis, hypertension, stroke, myocardial infarction, heart failure) should compare the results of preclinical studies with those of clinical trials. Full article

(This article belongs to the Special Issue Selected Papers from Resveratrol Regional Meeting 2015)

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779 KiB

Open AccessReview

Resveratrol and Myopathy

by Jean Bastin and Fatima Djouadi

Nutrients 2016, 8(5), 254; https://doi.org/10.3390/nu8050254 - 28 Apr 2016

Cited by 25 | Viewed by 8670

Abstract

Resveratrol is a natural polyphenolic compound produced by plants under various stress conditions. Resveratrol has been reported to exhibit antioxidant, anti-inflammatory, and anti-proliferative properties in mammalian cells and animal models, and might therefore exert pleiotropic beneficial effects in different pathophysiological states. More recently, [...] Read more.

Resveratrol is a natural polyphenolic compound produced by plants under various stress conditions. Resveratrol has been reported to exhibit antioxidant, anti-inflammatory, and anti-proliferative properties in mammalian cells and animal models, and might therefore exert pleiotropic beneficial effects in different pathophysiological states. More recently, resveratrol has also been shown to potentially target many mitochondrial metabolic pathways, including fatty acid β-oxidation or oxidative phosphorylation, leading to the up-regulation of the energy metabolism via signaling pathways involving PGC-1α, SIRT1, and/or AMP-kinase, which are not yet fully delineated. Some of resveratrol beneficial effects likely arise from its cellular effects in the skeletal muscle, which, surprisingly, has been given relatively little attention, compared to other target tissues. Here, we review the potential for resveratrol to ameliorate or correct mitochondrial metabolic deficiencies responsible for myopathies, due to inherited fatty acid β-oxidation or to respiratory chain defects, for which no treatment exists to date. We also review recent data supporting therapeutic effects of resveratrol in the Duchenne Muscular Dystrophy, a fatal genetic disease affecting the production of muscle dystrophin, associated to a variety of mitochondrial dysfunctions, which likely contribute to disease pathogenesis. Full article

(This article belongs to the Special Issue Selected Papers from Resveratrol Regional Meeting 2015)

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1567 KiB

Open AccessReview

Wine Resveratrol: From the Ground Up

by Luigi Bavaresco, Luigi Lucini, Matteo Busconi, Riccardo Flamini and Mirko De Rosso

Nutrients 2016, 8(4), 222; https://doi.org/10.3390/nu8040222 - 14 Apr 2016

Cited by 54 | Viewed by 7735

Abstract

The ability of the grapevine to activate defense mechanisms against some pathogens has been shown to be linked to the synthesis of resveratrol and other stilbenes by the plant (inducible viniferins). Metabolized viniferins may also be produced or modified by extracellular enzymes released [...] Read more.

The ability of the grapevine to activate defense mechanisms against some pathogens has been shown to be linked to the synthesis of resveratrol and other stilbenes by the plant (inducible viniferins). Metabolized viniferins may also be produced or modified by extracellular enzymes released by the pathogen in an attempt to eliminate undesirable toxic compounds. Because of the important properties of resveratrol, there is increasing interest in producing wines with higher contents of this compound and a higher nutritional value. Many biotic and abiotic elicitors can trigger the resveratrol synthesis in the berries, and some examples are reported. Under the same elicitation pressure, viticultural and enological factors can substantially affect the resveratrol concentration in the wine. The production of high resveratrol-containing grapes and wines relies on quality-oriented viticulture (suitable terroirs and sustainable cultural practices) and winemaking technologies that avoid degradation of the compound. In general, the oenological practices commonly used to stabilize wine after fermentation do not affect resveratrol concentration, which shows considerable stability. Finally the paper reports on two sirtuin genes (SIRT) expressed in grapevine leaves and berries and the role of resveratrol on the deacetylation activity of the encoded enzymes. Full article

(This article belongs to the Special Issue Selected Papers from Resveratrol Regional Meeting 2015)

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