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Special Issue "Resveratrol"

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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products".

Deadline for manuscript submissions: closed (31 August 2014)

Special Issue Editors

Guest Editor
Dr. Arthur S. Polans (Website)

Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, Wisconsin, USA
Interests: cancer; angiogenesis; biochemistry; drug development
Guest Editor
Dr. Paul van Ginkel

Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, Wisconsin, USA
Interests: cancer; angiogenesis; signal transduction pathways; drug development
Guest Editor
Dr. Veronika Somoza (Website)

Department of Nutritional and Physiological Chemistry and Christian Doppler Laboratory for Bioactive Aroma Compounds, University of Vienna, Vienna, Austria
Interests: food bioactives

Special Issue Information

Dear Colleagues,

Natural products are broadly defined as chemical substances made by living organisms, often associated with potentially beneficial applications. Although the use of natural products has ancient origins, their popularity should not be considered solely an historic default; in spite of ample time and effort by the worldwide pharmaceutical industry to employ high-throughput screening for the evaluation of combinatorial chemistry products, from 1981–2006 only 30% of New Chemical Entities covering all diseases were of synthetic origin, while the remaining compounds were largely natural products, their derivatives and mimics.

Of the more promising natural products under investigation, resveratrol has attracted the most attention because of its effects on cell signaling pathways relevant to disparate diseases. Resveratrol, a simple polyphenol (trans-3,5,4'-trihydroxystilbene), is found in many plants consumed in the normal diet such as grapes, berries and peanuts, as well as in other plant sources used as herbal medicines. In addition to cardioprotective and neuroprotective properties, resveratrol has been reported to provide protection against various cancers, diabetes, inflammatory diseases and senescence. Plant extracts containing resveratrol also have been reported to possess clinically relevant anti-oxidant activity.

However, it is not always clear how resveratrol causes different or even opposite effects in different cell types and in different diseases. For example, resveratrol can cause tumor cell death while it acts as an anti-apoptotic agent in nerve cells. Similarly, resveratrol is anti-angiogenic in many models of cancer yet pro-angiogenic in such maladies as myocardial infarction. Resveratrol can increase mitochondrial health in muscle cells while it induces
mitochondria-mediated apoptosis in tumor cells. It is apparent that the mechanisms of action of resveratrol need to be more fully elucidated and incorporated into larger cellular pathways to determine how it has such diverse activities in dissimilar cells and diseases. Ultimately, bona fide clinical trials also are needed to validate any claims of efficacy and to test improved formulations of resveratrol aimed at enhancing its bioavailability and expanding its modes of delivery.

To encompass the remarkable breadth of ongoing resveratrol research, articles covering a wide range of topics, including but not exclusive to metabolism, signaling pathways, pre-clinical studies, drug formulations and clinical trials are welcomed for inclusion in this Special Issue of Molecules.

Dr. Arthur S. Polans
Dr. Paul van Ginkel
Dr. Veronika Somoza
Guest Editors

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed Open Access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs).


Keywords

  • metabolism and bioavailability
  • cellular mechanisms of action
  • drug development
  • pre-clinical studies
  • analogs
  • clinical trials
  • nutrition and epidemiology

Published Papers (13 papers)

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Research

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Open AccessArticle Resveratrol Inhibits Trophoblast Apoptosis through Oxidative Stress in Preeclampsia-Model Rats
Molecules 2014, 19(12), 20570-20579; doi:10.3390/molecules191220570
Received: 5 September 2014 / Revised: 16 November 2014 / Accepted: 17 November 2014 / Published: 9 December 2014
Cited by 6 | PDF Full-text (1861 KB) | HTML Full-text | XML Full-text
Abstract
Resveratrol has been shown to be a therapeutic agent for cardiovascular disorders by maintaining a lower redox level in vivo through its anti-oxidant properties. Resveratrol can prevent cells from p53- and reactive oxygen species-dependent apoptosis induced by interleukin-1b. We identified an inhibitory [...] Read more.
Resveratrol has been shown to be a therapeutic agent for cardiovascular disorders by maintaining a lower redox level in vivo through its anti-oxidant properties. Resveratrol can prevent cells from p53- and reactive oxygen species-dependent apoptosis induced by interleukin-1b. We identified an inhibitory effect of resveratrol against oxidative stress and apoptosis using the TUNEL assay in NG-Nitro-l-arginine methyl ester-induced preeclampsia in rats. To investigate a possible association between resveratrol and the apoptosis caused by oxidative stress in vitro, assays for superoxide dismutase and malondialdehyde as well as flow cytometric analyses were conducted in HTR-8/SVneo cells after hypoxic treatment with or without resveratrol for 24 h. These data suggest that resveratrol significantly opposes the effects of oxidative stress in vivo and in vitro. Full article
(This article belongs to the Special Issue Resveratrol)
Open AccessArticle Resveratrol Modulates the Topoisomerase Inhibitory Potential of Doxorubicin in Human Colon Carcinoma Cells
Molecules 2014, 19(12), 20054-20072; doi:10.3390/molecules191220054
Received: 3 September 2014 / Revised: 24 November 2014 / Accepted: 25 November 2014 / Published: 1 December 2014
Cited by 5 | PDF Full-text (634 KB) | HTML Full-text | XML Full-text
Abstract
Resveratrol (RSV) is currently being widely discussed as potentially useful for anticancer therapy in combination with classical chemotherapeutics, e.g., the topoisomerase II (TOP II) poison doxorubicin (DOX). However, there is still a lack of knowledge of possible interference at the target enzyme, [...] Read more.
Resveratrol (RSV) is currently being widely discussed as potentially useful for anticancer therapy in combination with classical chemotherapeutics, e.g., the topoisomerase II (TOP II) poison doxorubicin (DOX). However, there is still a lack of knowledge of possible interference at the target enzyme, especially since RSV itself has recently been described to act as a TOP poison. We therefore sought to address the question whether RSV affects DOX-induced genotoxic and cytotoxic effects with special emphasis on TOP II in HT-29 colon carcinoma cells. RSV was found to counteract DOX-induced formation of DNA-TOP-intermediates at ≥100 µM for TOP IIα and at 250 µM for TOP IIβ. As a consequence, RSV modulated the DNA-strand breaking potential of DOX by mediating protective effects with an apparent maximum at 100 µM. At higher concentration ranges (≥200 µM) RSV diminished the intracellular concentrations of DOX. Nevertheless, the presence of RSV slightly enhanced the cytotoxic effects of DOX after 1.5 h and 24 h of incubation. Taken together, at least in cell culture RSV was found to affect the TOP-poisoning potential of DOX and to modulate its cytotoxic effectiveness. Thus, further studies are needed to clarify the impact of RSV on the therapeutic effectiveness of DOX under in vivo conditions. Full article
(This article belongs to the Special Issue Resveratrol)
Figures

Open AccessArticle Resveratrol Trimers from Seed Cake of Paeonia rockii
Molecules 2014, 19(12), 19549-19556; doi:10.3390/molecules191219549
Received: 11 October 2014 / Revised: 7 November 2014 / Accepted: 18 November 2014 / Published: 26 November 2014
Cited by 3 | PDF Full-text (220 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In the course of screening natural products for antibacterial activities, a total acetone extract of the seed cake of Paeonia rockii showed significant effects against bacterial strains. Bioactivity-guided fractionation of the EtOAc-soluble fraction of the total acetone extract resulted in the [...] Read more.
In the course of screening natural products for antibacterial activities, a total acetone extract of the seed cake of Paeonia rockii showed significant effects against bacterial strains. Bioactivity-guided fractionation of the EtOAc-soluble fraction of the total acetone extract resulted in the isolation and identification of five resveratrol trimers, including rockiiol C (1), gnetin H (2), suffruticosol A (3), suffruticosol B (4) and suffruticosol C (5). The relative configuration of these compounds was elucidated mainly by comprehensive 1D and 2D-NMR experiments. Compound 1 was a new compound. All isolated compounds exhibited strong antibacterial activities against Gram-positive bacteria. Full article
(This article belongs to the Special Issue Resveratrol)
Figures

Open AccessArticle The Sustained Delivery of Resveratrol or a Defined Grape Powder Inhibits New Blood Vessel Formation in a Mouse Model of Choroidal Neovascularization
Molecules 2014, 19(11), 17578-17603; doi:10.3390/molecules191117578
Received: 26 August 2014 / Revised: 20 October 2014 / Accepted: 22 October 2014 / Published: 30 October 2014
Cited by 5 | PDF Full-text (3975 KB) | HTML Full-text | XML Full-text
Abstract
The objective of this study was to determine whether resveratrol or a defined, reconstituted grape powder can attenuate the formation of new blood vessels in a mouse model of choroidal neovascularization (CNV). To accomplish this objective, C57BL/6J mice were randomized into control [...] Read more.
The objective of this study was to determine whether resveratrol or a defined, reconstituted grape powder can attenuate the formation of new blood vessels in a mouse model of choroidal neovascularization (CNV). To accomplish this objective, C57BL/6J mice were randomized into control or treatment groups which received either resveratrol or grape powder by daily oral gavage, resveratrol or grape powder delivered ad libitum through the drinking water, or resveratrol by slow release via implanted osmotic pumps. A laser was used to rupture Bruch’s membrane to induce CNV which was then detected in sclerochoroidal eyecups stained with antibodies against intercellular adhesion molecule-2. CNV area was measured using fluorescence microscopy and Image J software. Ad libitum delivery of both resveratrol and grape powder was shown to significantly reduce the extent of CNV by 68% and 57%, respectively. Parallel experiments conducted in vitro demonstrated that resveratrol activates p53 and inactivates Akt/protein kinase B in choroidal endothelial cells, contributing to its anti-proliferative and anti-migratory properties. In addition resveratrol was shown to inhibit the formation of endothelial cell networks, augmenting its overall anti-angiogenic effects. The non-toxic nature of resveratrol makes it an especially attractive candidate for the prevention and/or treatment of CNV. Full article
(This article belongs to the Special Issue Resveratrol)
Figures

Open AccessArticle Impact of Trans-Resveratrol-Sulfates and -Glucuronides on Endothelial Nitric Oxide Synthase Activity, Nitric Oxide Release and Intracellular Reactive Oxygen Species
Molecules 2014, 19(10), 16724-16736; doi:10.3390/molecules191016724
Received: 29 August 2014 / Revised: 30 September 2014 / Accepted: 13 October 2014 / Published: 17 October 2014
Cited by 8 | PDF Full-text (920 KB) | HTML Full-text | XML Full-text
Abstract
Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a polyphenolic natural product mainly present in grape skin, berries and peanuts. In the vasculature resveratrol is thought to boost endothelial function by increasing endothelial nitric oxide synthase (eNOS) expression, by enhancing eNOS activity, and by reduction of reactive [...] Read more.
Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a polyphenolic natural product mainly present in grape skin, berries and peanuts. In the vasculature resveratrol is thought to boost endothelial function by increasing endothelial nitric oxide synthase (eNOS) expression, by enhancing eNOS activity, and by reduction of reactive oxygen species (ROS) levels. Recent studies show that dietary resveratrol is metabolized in the liver and intestine into resveratrol-sulfate and -glucuronide derivatives questioning the relevance of multiple reported mechanistic in vitro data on resveratrol. In this study, we compare side by side different physiologically relevant resveratrol metabolites (resveratrol sulfates- and -glucuronides) and their parent compound in their influence on eNOS enzyme activity, endothelial NO release, and intracellular ROS levels. In contrast to resveratrol, none of the tested resveratrol metabolites elevated eNOS enzyme activity and endothelial NO release or affected intracellular ROS levels, leaving the possibility that not tested metabolites are active and able to explain in vivo findings. Full article
(This article belongs to the Special Issue Resveratrol)
Figures

Open AccessArticle New Water-Soluble Carbamate Ester Derivatives of Resveratrol
Molecules 2014, 19(10), 15900-15917; doi:10.3390/molecules191015900
Received: 27 August 2014 / Revised: 22 September 2014 / Accepted: 24 September 2014 / Published: 1 October 2014
Cited by 7 | PDF Full-text (416 KB) | HTML Full-text | XML Full-text
Abstract
Low bioavailability severely hinders exploitation of the biomedical potential of resveratrol. Extensive phase-II metabolism and poor water solubility contribute to lowering the concentrations of resveratrol in the bloodstream after oral administration. Prodrugs may provide a solution—protection of the phenolic functions hinders conjugative [...] Read more.
Low bioavailability severely hinders exploitation of the biomedical potential of resveratrol. Extensive phase-II metabolism and poor water solubility contribute to lowering the concentrations of resveratrol in the bloodstream after oral administration. Prodrugs may provide a solution—protection of the phenolic functions hinders conjugative metabolism and can be exploited to modulate the physicochemical properties of the compound. We report here the synthesis and characterization of carbamate ester derivatives of resveratrol bearing on each nitrogen atom a methyl group and either a methoxy-poly(ethylene glycol)-350 (mPEG-350) or a butyl-glucosyl promoiety conferring high water solubility. Ex vivo absorption studies revealed that the butyl-glucosyl conjugate, unlike the mPEG-350 one, is able to permeate the intestinal wall. In vivo pharmacokinetics confirmed absorption after oral administration and showed that no hydrolysis of the carbamate groups takes place. Thus, sugar groups can be attached to resveratrol to obtain soluble derivatives maintaining to some degree the ability to permeate biomembranes, perhaps by facilitated or active transport. Full article
(This article belongs to the Special Issue Resveratrol)
Figures

Open AccessArticle Anti-Stress Action of an Orally-Given Combination of Resveratrol, β-Glucan, and Vitamin C
Molecules 2014, 19(9), 13724-13734; doi:10.3390/molecules190913724
Received: 17 July 2014 / Revised: 30 August 2014 / Accepted: 1 September 2014 / Published: 3 September 2014
PDF Full-text (858 KB) | HTML Full-text | XML Full-text
Abstract
Stress has repeatedly been found to reduce the abilities of the immune system to fight against individual attacks. The current dissatisfaction with classical medications has led to more attention being focused on natural molecules. As recent studies have suggested that some bioactive [...] Read more.
Stress has repeatedly been found to reduce the abilities of the immune system to fight against individual attacks. The current dissatisfaction with classical medications has led to more attention being focused on natural molecules. As recent studies have suggested that some bioactive molecules can have synergistic effects in stimulation of immune system and reduction of stress, we have evaluated the stress-reducing effects of the resveratrol-β-glucan-vitamin C combination. We found that compared to its individual components, this combination was the strongest reducer of stress-related symptoms, including corticosterone levels and IL-6, IL-12 and IFN-γ production. Full article
(This article belongs to the Special Issue Resveratrol)
Open AccessArticle Quantification of the Resveratrol Analogs trans-2,3-Dimethoxy-stilbene and trans-3,4-Dimethoxystilbene in Rat Plasma: Application to Pre-Clinical Pharmacokinetic Studies
Molecules 2014, 19(7), 9577-9590; doi:10.3390/molecules19079577
Received: 4 May 2014 / Revised: 26 June 2014 / Accepted: 28 June 2014 / Published: 7 July 2014
Cited by 1 | PDF Full-text (821 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
trans-2,3-Dimethoxystilbene (2,3-DMS) and trans-3,4-dimethoxystilbene (3,4-DMS) are two synthetic resveratrol (trans-3,5,4'-trihydroxystilbene) analogs. In this study, a simple HPLC method was developed and validated to determine 2,3-DMS and 3,4-DMS in rat plasma. Chromatographic separation was obtained with a reversed-phase HPLC [...] Read more.
trans-2,3-Dimethoxystilbene (2,3-DMS) and trans-3,4-dimethoxystilbene (3,4-DMS) are two synthetic resveratrol (trans-3,5,4'-trihydroxystilbene) analogs. In this study, a simple HPLC method was developed and validated to determine 2,3-DMS and 3,4-DMS in rat plasma. Chromatographic separation was obtained with a reversed-phase HPLC column through a 12.5-min gradient delivery of a mixture of acetonitrile and water at the flow rate of 1.5 mL/min at 50 °C. The lower limit of quantification was 10 ng/mL. After successful validation, the pharmacokinetic profiles of 2,3-DMS and 3,4-DMS were subsequently studied in Sprague-Dawley rats. Upon single intravenous administration (4 mg/kg), 2,3-DMS had a medium volume of distribution of the central compartment (Vc = 2.71 ± 0.51 L/kg), quite rapid clearance (Cl = 52.0 ± 7.0 mL/min/kg), moderate mean transit time (MTT0→last = 131.0 ± 4.5 min) but a fairly long terminal elimination half-life (t1/2 λZ = 288.9 ± 92.9 min). Interestingly, 3,4-DMS displayed a pharmacokinetic profile apparently distinct from 2,3-DMS and it had more extensive distribution (Vc = 5.58 ± 1.73 L/kg), faster clearance (Cl = 143.4 ± 40.5 mL/min/kg) and shorter residence (MTT0→last = 61.4 ± 27.1 min). Following single oral administration (10 mg/kg), 2,3-DMS had low and erratic plasma exposure (Cmax = 37.5 ± 23.7 ng/mL) and poor oral bioavailability (2.22% ± 2.13%) while the oral bioavailability of 3,4-DMS was even poorer than 2,3-DMS. Clearly, the location of the methoxy groups had a significant impact on the pharmacokinetics of resveratrol analogs. This study provided useful information for the design of resveratrol derivatives in future study. Full article
(This article belongs to the Special Issue Resveratrol)

Review

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Open AccessReview Resveratrol: Anti-Obesity Mechanisms of Action
Molecules 2014, 19(11), 18632-18655; doi:10.3390/molecules191118632
Received: 9 September 2014 / Revised: 28 October 2014 / Accepted: 10 November 2014 / Published: 14 November 2014
Cited by 24 | PDF Full-text (1380 KB) | HTML Full-text | XML Full-text
Abstract
Resveratrol is a non-flavonoid polyphenol which belongs to the stilbenes group and is produced naturally in several plants in response to injury or fungal attack. Resveratrol has been recently reported as preventing obesity. The present review aims to compile the evidence concerning [...] Read more.
Resveratrol is a non-flavonoid polyphenol which belongs to the stilbenes group and is produced naturally in several plants in response to injury or fungal attack. Resveratrol has been recently reported as preventing obesity. The present review aims to compile the evidence concerning the potential mechanisms of action which underlie the anti-obesity effects of resveratrol, obtained either in cultured cells lines and animal models. Published studies demonstrate that resveratrol has an anti-adipogenic effect. A good consensus concerning the involvement of a down-regulation of C/EBPα and PPARγ in this effect has been reached. Also, in vitro studies have demonstrated that resveratrol can increase apoptosis in mature adipocytes. Furthermore, different metabolic pathways involved in triacylglycerol metabolism in white adipose tissue have been shown to be targets for resveratrol. Both the inhibition of de novo lipogenesis and adipose tissue fatty acid uptake mediated by lipoprotein lipase play a role in explaining the reduction in body fat which resveratrol induces. As far as lipolysis is concerned, although this compound per se seems to be unable to induce lipolysis, it increases lipid mobilization stimulated by β-adrenergic agents. The increase in brown adipose tissue thermogenesis, and consequently the associated energy dissipation, can contribute to explaining the body-fat lowering effect of resveratrol. In addition to its effects on adipose tissue, resveratrol can also acts on other organs and tissues. Thus, it increases mitochondriogenesis and consequently fatty acid oxidation in skeletal muscle and liver. This effect can also contribute to the body-fat lowering effect of this molecule. Full article
(This article belongs to the Special Issue Resveratrol)
Open AccessReview Compared Binding Properties between Resveratrol and Other Polyphenols to Plasmatic Albumin: Consequences for the Health Protecting Effect of Dietary Plant Microcomponents
Molecules 2014, 19(11), 17066-17077; doi:10.3390/molecules191117066
Received: 30 August 2014 / Revised: 7 October 2014 / Accepted: 9 October 2014 / Published: 24 October 2014
Cited by 6 | PDF Full-text (441 KB) | HTML Full-text | XML Full-text
Abstract
Phytophenols are considered to have beneficial effects towards human physiology. They are food microcomponents with potent chemopreventive properties towards the most three frequent contemporary human diseases, e.g., cardiovascular alterations, cancer and neurodegenerative pathologies. Related to this, the plasmatic form and plasmatic level [...] Read more.
Phytophenols are considered to have beneficial effects towards human physiology. They are food microcomponents with potent chemopreventive properties towards the most three frequent contemporary human diseases, e.g., cardiovascular alterations, cancer and neurodegenerative pathologies. Related to this, the plasmatic form and plasmatic level of plant polyphenols in the body circulation are crucial for their efficiency. Thus, determinations of the binding process of resveratrol and of common flavonoids produced by major edible plants, berries and fruits to plasma proteins are essential. The interactions between resveratrol and albumin, a major plasma protein, were compared with those already published, involving curcumin, genistein, quercetin and other well-known food-containing polyphenols. The approaches used are usually intrinsic fluorescence intensity changes, quenching of protein intrinsic fluorescence and infrared spectroscopy. It appears that: (1) all of the studied polyphenols interact with albumin; (2) while most of the studied polyphenols interact at one albumin binding site, there are two different types of resveratrol binding sites for bovine serum albumin, one with the highest affinity (apparent KD of 4 µM) with a stoichiometry of one per monomer and a second with a lower affinity (apparent KD of 20 µM) with also a stoichiometry of one per monomer; (3) at least one binding site is in the vicinity of one tryptophanyl residue of bovine serum albumin; and (4) resveratrol binding to bovine serum albumin produces a very small structural conformation change of the polypeptide chain. These results support a role played by polyphenols-albumin interactions in the plasma for the bio-activities of these food microcomponents in the body. Full article
(This article belongs to the Special Issue Resveratrol)
Open AccessReview Enhancing the Delivery of Resveratrol in Humans: If Low Bioavailability is the Problem, What is the Solution?
Molecules 2014, 19(11), 17154-17172; doi:10.3390/molecules191117154
Received: 17 September 2014 / Revised: 21 October 2014 / Accepted: 21 October 2014 / Published: 24 October 2014
Cited by 18 | PDF Full-text (265 KB) | HTML Full-text | XML Full-text
Abstract
Resveratrol has emerged as a leading candidate for improving healthspan through potentially slowing the aging process and preventing chronic diseases. The poor bioavailability of resveratrol in humans has been a major concern for translating basic science findings into clinical utility. Although a [...] Read more.
Resveratrol has emerged as a leading candidate for improving healthspan through potentially slowing the aging process and preventing chronic diseases. The poor bioavailability of resveratrol in humans has been a major concern for translating basic science findings into clinical utility. Although a number of positive findings have emerged from human clinical trials, there remain many conflicting results, which may partially be attributed to the dosing protocols used. A number of theoretical solutions have been developed to improve the bioavailability of resveratrol, including consumption with various foods, micronized powders, combining it with additional phytochemicals, controlled release devices, and nanotechnological formulations. While laboratory models indicate these approaches all have potential to improve bioavailability of resveratrol and optimize its clinical utility, there is surprisingly very little data regarding the bioavailability of resveratrol in humans. If bioavailability is indeed a limitation in the clinical utility of resveratrol, there is a need to further explore methods to optimize bioavailability in humans. This review summarizes the current bioavailability data, focusing on data from humans, and provides suggested directions for future research in this realm. Full article
(This article belongs to the Special Issue Resveratrol)
Open AccessReview Resveratrol and Endothelial Nitric Oxide
Molecules 2014, 19(10), 16102-16121; doi:10.3390/molecules191016102
Received: 18 August 2014 / Revised: 21 September 2014 / Accepted: 25 September 2014 / Published: 9 October 2014
Cited by 9 | PDF Full-text (959 KB) | HTML Full-text | XML Full-text
Abstract
Nitric oxide (NO) derived from the endothelial NO synthase (eNOS) has antihypertensive, antithrombotic, anti-atherosclerotic and antiobesogenic properties. Resveratrol is a polyphenol phytoalexin with multiple cardiovascular and metabolic effects. Part of the beneficial effects of resveratrol are mediated by eNOS. Resveratrol stimulates NO [...] Read more.
Nitric oxide (NO) derived from the endothelial NO synthase (eNOS) has antihypertensive, antithrombotic, anti-atherosclerotic and antiobesogenic properties. Resveratrol is a polyphenol phytoalexin with multiple cardiovascular and metabolic effects. Part of the beneficial effects of resveratrol are mediated by eNOS. Resveratrol stimulates NO production from eNOS by a number of mechanisms, including upregulation of eNOS expression, stimulation of eNOS enzymatic activity and reversal of eNOS uncoupling. In addition, by reducing oxidative stress, resveratrol prevents oxidative NO inactivation by superoxide thereby enhancing NO bioavailability. Molecular pathways underlying these effects of resveratrol involve SIRT1, AMPK, Nrf2 and estrogen receptors. Full article
(This article belongs to the Special Issue Resveratrol)
Open AccessReview Experimental Studies of the Molecular Pathways Regulated by Exercise and Resveratrol in Heart, Skeletal Muscle and the Vasculature
Molecules 2014, 19(9), 14919-14947; doi:10.3390/molecules190914919
Received: 20 August 2014 / Revised: 10 September 2014 / Accepted: 10 September 2014 / Published: 18 September 2014
Cited by 8 | PDF Full-text (1014 KB) | HTML Full-text | XML Full-text
Abstract
Regular exercise contributes to healthy aging and the prevention of chronic disease. Recent research has focused on the development of molecules, such as resveratrol, that activate similar metabolic and stress response pathways as exercise training. In this review, we describe the effects [...] Read more.
Regular exercise contributes to healthy aging and the prevention of chronic disease. Recent research has focused on the development of molecules, such as resveratrol, that activate similar metabolic and stress response pathways as exercise training. In this review, we describe the effects of exercise training and resveratrol on some of the organs and tissues that act in concert to transport oxygen throughout the body. In particular, we focus on animal studies that investigate the molecular signaling pathways induced by these interventions. We also compare and contrast the effects of exercise and resveratrol in diseased states. Full article
(This article belongs to the Special Issue Resveratrol)

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