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Special Issue "Benefits of Resveratrol Supplementation"

A special issue of Nutrients (ISSN 2072-6643).

Deadline for manuscript submissions: closed (31 October 2018)

Special Issue Editors

Guest Editor
Prof. Dr. María P. Portillo

Nutrition and Obesity Group, Department of Nutrition and Food Science, Faculty of Pharmacy and Lucio Lascaray Research Center, University of the Basque Country (UPV/EHU), Vitoria, Spain
CIBER Fisiopatología Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
Website 1 | Website 2 | Website 3 | E-Mail
Interests: Phenolic compounds, obesity, insulin resistance, liver steatosis
Guest Editor
Dr. Alfredo Fernandez-Quintela

CIBER Fisiopatología Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain
Website 1 | Website 2 | Website 3 | E-Mail
Interests: obesity; steatosis; insulin resistance; adipose tissue; browning; liver; polyphenols

Special Issue Information

Dear Colleagues,

In recent years, great attention has been paid to polyphenols due to their positive effects on health. One of the most widely-studied phenolic compounds is resveratrol. This molecule, which is naturally present in some foods, shows beneficial effects on various physiological and biochemical processes, thus representing a potential tool for the prevention or the treatment of diseases highly prevalent in our society. Several of these beneficial effects have been observed in human beings, but others only in pre-clinical studies so far, and therefore, it is mandatory to continue with the scientific research in this field. Indeed, new knowledge concerning these issues could enable the development of novel functional foods or nutraceuticals, incorporating resveratrol, suitable for preventing or treating diseases such as cancer, cardiovascular diseases, obesity, dislipemia, insulin resistance and diabetes, liver diseases, etc.

It is our great pleasure to invite researchers to provide manuscripts either describing original research or providing and up-to-date review of the scientific literature for a Special Issue of Nutrients on "Benefits of Resveratrol Supplementation”. Manuscripts can present recent advances on the knowledge on resveratrol effects on health, including mechanisms of action, dose-response patterns, how to improve bioavailability, combinatorial strategies, population group targets, health claims and with other bioactive molecules.

Prof. María P. Portillo
Dr. Alfredo Fernandez-Quintela
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Nutrients 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 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Resveratrol supplementation
  • Mechanisms of action
  • Bioavailability
  • Resveratrol metabolites
  • Combinatorial strategies
  • Benefits on health
  • Western society diseases
  • Prevention
  • Treatment

Published Papers (16 papers)

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Research

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Open AccessArticle
Protective Effect of Resveratrol against Ischemia-Reperfusion Injury via Enhanced High Energy Compounds and eNOS-SIRT1 Expression in Type 2 Diabetic Female Rat Heart
Nutrients 2019, 11(1), 105; https://doi.org/10.3390/nu11010105
Received: 26 November 2018 / Revised: 19 December 2018 / Accepted: 28 December 2018 / Published: 6 January 2019
Cited by 3 | PDF Full-text (1444 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Type 2 diabetic women have a high risk of mortality via myocardial infarction even with anti-diabetic treatments. Resveratrol (RSV) is a natural polyphenol, well-known for its antioxidant property, which has also shown interesting positive effects on mitochondrial function. Therefore, we aim to investigate [...] Read more.
Type 2 diabetic women have a high risk of mortality via myocardial infarction even with anti-diabetic treatments. Resveratrol (RSV) is a natural polyphenol, well-known for its antioxidant property, which has also shown interesting positive effects on mitochondrial function. Therefore, we aim to investigate the potential protective effect of 1 mg/kg/day of RSV on high energy compounds, during myocardial ischemia-reperfusion in type 2 diabetic female Goto-Kakizaki (GK) rats. For this purpose, we used 31P magnetic resonance spectroscopy in isolated perfused heart experiments, with a simultaneous measurement of myocardial function and coronary flow. RSV enhanced adenosine triphosphate (ATP) and phosphocreatine (PCr) contents in type 2 diabetic hearts during reperfusion, in combination with better functional recovery. Complementary biochemical analyses showed that RSV increased creatine, total adenine nucleotide heart contents and citrate synthase activity, which could be involved in better mitochondrial functioning. Moreover, improved coronary flow during reperfusion by RSV was associated with increased eNOS, SIRT1, and P-Akt protein expression in GK rat hearts. In conclusion, RSV induced cardioprotection against ischemia-reperfusion injury in type 2 diabetic female rats via increased high energy compound contents and expression of protein involved in NO pathway. Thus, RSV presents high potential to protect the heart of type 2 diabetic women from myocardial infarction. Full article
(This article belongs to the Special Issue Benefits of Resveratrol Supplementation)
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Open AccessArticle
Solid Dispersion of Resveratrol Supported on Magnesium DiHydroxide ([email protected]) Microparticles Improves Oral Bioavailability
Nutrients 2018, 10(12), 1925; https://doi.org/10.3390/nu10121925
Received: 24 October 2018 / Revised: 21 November 2018 / Accepted: 26 November 2018 / Published: 5 December 2018
Cited by 1 | PDF Full-text (1997 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Resveratrol, because of its low solubility in water and its high membrane permeability, is collocated in the second class of the biopharmaceutical classification system, with limited bioavailability due to its dissolution rate. Solid dispersion of resveratrol supported on Magnesium DiHydroxide ([email protected]) was evaluated [...] Read more.
Resveratrol, because of its low solubility in water and its high membrane permeability, is collocated in the second class of the biopharmaceutical classification system, with limited bioavailability due to its dissolution rate. Solid dispersion of resveratrol supported on Magnesium DiHydroxide ([email protected]) was evaluated to improve solubility and increase bioavailability of resveratrol. Fluorimetric microscopy analysis displays three types of microparticles with similar size: Type 1 that emitted preferably fluorescence at 445 nm with bandwidth of 50 nm, type 2 that emitted preferably fluorescence at 605 nm with bandwidth of 70 nm and type 3 that is non-fluorescent. Micronized pure resveratrol displays only microparticles type 1 whereas type 3 are associated to pure magnesium dihydroxide. Dissolution test in simulated gastric environment resveratrol derived from [email protected] in comparison to resveratrol alone displayed better solubility. A 3-fold increase of resveratrol bioavailability was observed after oral administration of 50 mg/kg of resveratrol from [email protected] in rabbits. We hypothesize that type 2 microparticles represent magnesium dihydroxide microparticles with a resveratrol shell and that they are responsible for the improved resveratrol solubility and bioavailability of [email protected] Full article
(This article belongs to the Special Issue Benefits of Resveratrol Supplementation)
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Open AccessFeature PaperArticle
Study of Potential Anti-Inflammatory Effects of Red Wine Extract and Resveratrol through a Modulation of Interleukin-1-Beta in Macrophages
Nutrients 2018, 10(12), 1856; https://doi.org/10.3390/nu10121856
Received: 30 October 2018 / Revised: 20 November 2018 / Accepted: 22 November 2018 / Published: 1 December 2018
Cited by 1 | PDF Full-text (2886 KB) | HTML Full-text | XML Full-text
Abstract
Inflammation has been described as an initiator event of major diseases with significant impacts in terms of public health including in cardiovascular disease, autoimmune disorders, eye diseases, age-related diseases, and the occurrence of cancers. A preventive action to reduce the key processes leading [...] Read more.
Inflammation has been described as an initiator event of major diseases with significant impacts in terms of public health including in cardiovascular disease, autoimmune disorders, eye diseases, age-related diseases, and the occurrence of cancers. A preventive action to reduce the key processes leading to inflammation could be an advantageous approach to reducing these associated pathologies. Many studies have reported the value of polyphenols such as resveratrol in counteracting pro-inflammatory cytokines. We have previously shown the potential of red wine extract (RWE) and the value of its qualitative and quantitative polyphenolic composition to prevent the carcinogenesis process. In this study, we addressed a new effect of RWE in inflammation through a modulation of IL-1β secretion and the NLRP3 inflammasome pathway. NLRP3 inflammasome requires two signals, priming to increase the synthesis of NLRP3 and pro-IL-1β proteins and activation, which activates NLRP3. Inflammasome formation is triggered by a range of substances such as lipopolysaccharide (LPS). Using two different macrophages, one of which does not express the adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD), which is essential to form active inflammasome complexes that produce IL-1β, we show that RWE decreases IL-1 β secretion and gene expression whatever line is used. Moreover, this strong reduction of pro-inflammatory IL-1β is associated with a decrease of NLRP3 and, in J774A, ASC protein expression, which depends on the choice of activator ATP or nigericin. Full article
(This article belongs to the Special Issue Benefits of Resveratrol Supplementation)
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Open AccessFeature PaperArticle
In Vitro Anticancer Properties of Table Grape Powder Extract (GPE) in Prostate Cancer
Nutrients 2018, 10(11), 1804; https://doi.org/10.3390/nu10111804
Received: 1 November 2018 / Revised: 12 November 2018 / Accepted: 15 November 2018 / Published: 20 November 2018
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Abstract
Although the link between diet and cancer is complex, epidemiological data confirm that diet is a risk factor for prostate cancer and indicate a reduced prostate cancer incidence associated with a diet rich in vegetables and fruits. Because of the known protective effect [...] Read more.
Although the link between diet and cancer is complex, epidemiological data confirm that diet is a risk factor for prostate cancer and indicate a reduced prostate cancer incidence associated with a diet rich in vegetables and fruits. Because of the known protective effect of grape seed extract (GSE) against prostate cancer, we evaluated the effects of grape powder extract (GPE) on cell viability, proliferation, and metastatic capability. Importantly, we explored the possible novel mechanism of GPE through metastasis-associated protein 1 (MTA1) downregulation in prostate cancer, since our previous studies indicated resveratrol (Res)- and pterostilbene (Pter)-induced MTA1-mediated anticancer activities in prostate cancer. We found that GPE inhibited the cell viability and growth of prostate cancer cells only at high 100 μg/mL concentrations. However, at low 1.5–15 μg/mL concentrations, GPE significantly reduced the colony formation and wound healing capabilities of both DU145 and PC3M cells. Moreover, we found that GPE inhibited MTA1 in a dose-dependent manner in these cells, albeit with considerably less potency than Res and Pter. These results indicate that stilbenes such as Res and Pter specifically and potently inhibit MTA1 and MTA1-associated proteins compared to GPE, which contains low concentrations of Res and mainly consists of other flavonoids and anthocyanidins. Our findings support continued interest in GPE as a chemopreventive and anti-cancer agent against prostate cancer but also emphasize the unique and specific properties of stilbenes on MTA1-mediated anticancer effects on prostate cancer. Full article
(This article belongs to the Special Issue Benefits of Resveratrol Supplementation)
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Open AccessArticle
Potential Involvement of Peripheral Leptin/STAT3 Signaling in the Effects of Resveratrol and Its Metabolites on Reducing Body Fat Accumulation
Nutrients 2018, 10(11), 1757; https://doi.org/10.3390/nu10111757
Received: 30 October 2018 / Revised: 11 November 2018 / Accepted: 12 November 2018 / Published: 14 November 2018
Cited by 2 | PDF Full-text (1485 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Bioactive compounds such as polyphenols have increased in importance in recent years, and among them, resveratrol (3,5,4′-trihydroxy-trans-stilbene) has generated great interest as an anti-obesity agent. Recent investigations have highlighted the importance of leptin signaling in lipid metabolism in peripheral organs. The aims of [...] Read more.
Bioactive compounds such as polyphenols have increased in importance in recent years, and among them, resveratrol (3,5,4′-trihydroxy-trans-stilbene) has generated great interest as an anti-obesity agent. Recent investigations have highlighted the importance of leptin signaling in lipid metabolism in peripheral organs. The aims of this study were (1) to investigate whether resveratrol can reduce fat accumulation in peripheral tissues by increasing their leptin sensitivity and (2) to identify which resveratrol-derived circulating metabolites are potentially involved in these metabolic effects. Serum leptin levels and the leptin signaling pathway were assessed in diet-induced obese rats. Moreover, serum metabolites of resveratrol were studied by ultra-high performance liquid chromatography–mass spectrometry (UHPLC-MSn). The daily consumption of 200 mg/kg of resveratrol, but not doses of 50 and 100 mg/kg, reduced body weight and fat accumulation in obese rats and restored leptin sensitivity in the periphery. These effects were due to increases in sirtuin 1 activity in the liver, leptin receptors in muscle and protection against endoplasmic reticulum (ER)-stress in adipose tissue. In general, the resveratrol metabolites associated with these beneficial effects were derived from both phase II and microbiota metabolism, although only those derived from microbiota increased proportionally with the administered dose of resveratrol. In conclusion, resveratrol reversed leptin resistance caused by diet-induced obesity in peripheral organs using tissue-specific mechanisms. Full article
(This article belongs to the Special Issue Benefits of Resveratrol Supplementation)
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Open AccessArticle
Effects of Resveratrol on the Renin-Angiotensin System in the Aging Kidney
Nutrients 2018, 10(11), 1741; https://doi.org/10.3390/nu10111741
Received: 8 October 2018 / Revised: 2 November 2018 / Accepted: 9 November 2018 / Published: 12 November 2018
Cited by 2 | PDF Full-text (12458 KB) | HTML Full-text | XML Full-text
Abstract
The renin-angiotensin system (RAS), especially the angiotensin II (Ang II)/angiotensin II type 1 receptor (AT1R) axis, plays an important role in the aging process of the kidney, through increased tissue reactive oxygen species production and progressively increased oxidative stress. In contrast, the angiotensin [...] Read more.
The renin-angiotensin system (RAS), especially the angiotensin II (Ang II)/angiotensin II type 1 receptor (AT1R) axis, plays an important role in the aging process of the kidney, through increased tissue reactive oxygen species production and progressively increased oxidative stress. In contrast, the angiotensin 1-7 (Ang 1-7)/Mas receptor (MasR) axis, which counteracts the effects of Ang II, is protective for end-organ damage. To evaluate the ability of resveratrol (RSV) to modulate the RAS in aging kidneys, eighteen-month-old male C57BL/6 mice were divided into two groups that received either normal mouse chow or chow containing resveratrol, for six months. Renal expressions of RAS components, as well as pro- and antioxidant enzymes, were measured and mouse kidneys were isolated for histopathology. Resveratrol-treated mice demonstrated better renal function and reduced albuminuria, with improved renal histologic findings. Resveratrol suppressed the Ang II/AT1R axis and enhanced the AT2R/Ang 1-7/MasR axis. Additionally, the expression of nicotinamide adenine dinucleotide phosphate oxidase 4, 8-hydroxy-2′-deoxyguanosine, 3-nitrotyrosine, collagen IV, and fibronectin was decreased, while the expression of endothelial nitric oxide synthase and superoxide dismutase 2 was increased by resveratrol treatment. These findings demonstrate that resveratrol exerts protective effects on aging kidneys by reducing oxidative stress, inflammation, and fibrosis, through Ang II suppression and MasR activation. Full article
(This article belongs to the Special Issue Benefits of Resveratrol Supplementation)
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Open AccessArticle
Tissular Distribution and Metabolism of trans-ε-Viniferin after Intraperitoneal Injection in Rat
Nutrients 2018, 10(11), 1660; https://doi.org/10.3390/nu10111660
Received: 11 October 2018 / Revised: 26 October 2018 / Accepted: 30 October 2018 / Published: 4 November 2018
Cited by 1 | PDF Full-text (580 KB) | HTML Full-text | XML Full-text
Abstract
Background: Recent studies showed that trans-ε-viniferin (ε-viniferin), a trans-resveratrol dehydrodimer, has anti-inflammatory and anti-obesity effects in rodents. The main purpose of this work was to assess the tissue distribution study of ε-viniferin and its metabolites after intraperitoneal (IP) administration in rat. [...] Read more.
Background: Recent studies showed that trans-ε-viniferin (ε-viniferin), a trans-resveratrol dehydrodimer, has anti-inflammatory and anti-obesity effects in rodents. The main purpose of this work was to assess the tissue distribution study of ε-viniferin and its metabolites after intraperitoneal (IP) administration in rat. Methods: After IP injection of 50 mg/kg, ε-viniferin and its metabolites were identified and quantified in plasma, liver, kidneys, adipose tissues, urine, and faeces by Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS). Results: ε-Viniferin underwent a rapid hepatic metabolism mostly to glucuronides but also to a lesser extent to sulphate derivatives. The highest glucuronide concentrations were found in liver followed by plasma and kidneys whereas only traces amounts were found in adipose tissues. In contrast the highest ε-viniferin areas under concentration (AUC) and mean residence times (MRT) values were found in white adipose tissues. Finally, much lower levels of ε-viniferin or its metabolites were found in urine than in faeces, suggesting that biliary excretion is the main elimination pathway. Conclusion: A rapid and large metabolism of ε-viniferin and a high bioaccumulation in white adipose tissues were observed. Thus, these tissues could be a reservoir of the native form of ε-viniferin that could allow its slow release and a sustained presence within the organism. Full article
(This article belongs to the Special Issue Benefits of Resveratrol Supplementation)
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Open AccessArticle
Do the Effects of Resveratrol on Thermogenic and Oxidative Capacities in IBAT and Skeletal Muscle Depend on Feeding Conditions?
Nutrients 2018, 10(10), 1446; https://doi.org/10.3390/nu10101446
Received: 14 September 2018 / Revised: 28 September 2018 / Accepted: 29 September 2018 / Published: 6 October 2018
Cited by 1 | PDF Full-text (3108 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The aim of this study was to compare the effects of mild energy restriction and resveratrol on thermogenic and oxidative capacity in interscapular brown adipose tissue (IBAT) and in skeletal muscle. Rats were fed a high-fat high-sucrose diet for six weeks, and divided [...] Read more.
The aim of this study was to compare the effects of mild energy restriction and resveratrol on thermogenic and oxidative capacity in interscapular brown adipose tissue (IBAT) and in skeletal muscle. Rats were fed a high-fat high-sucrose diet for six weeks, and divided into four experimental groups fed a standard diet: a control group, a resveratrol-treated group, an energy-restricted group and an energy-restricted group treated with resveratrol. Weights of IBAT, gastrocnemius muscle and fat depots were measured. Activities of carnitine palmitoyltransferase (CPT) and citrate synthase (CS), protein levels of sirtuin (SIRT1 and 3), uncoupling proteins (UCP1 and 3), glucose transporter (GLUT4), mitochondrial transcription factor (TFAM), nuclear respiratory factor (NRF1), peroxisome proliferator-activated receptor (PPARα) and AMP activated protein kinase (AMPK) and peroxisome proliferator-activated receptor gamma coactivator (PGC1α) activation were measured. No changes in IBAT and gastrocnemius weights were found. Energy-restriction, but not resveratrol, decreased the weights of adipose depots. In IBAT, resveratrol enhanced thermogenesis activating the SIRT1/PGC1α/PPARα axis. Resveratrol also induced fatty acid oxidation and glucose uptake. These effects were similar when resveratrol was combined with energy restriction. In the case of gastrocnemius muscle, the effects were not as clear as in the case of IBAT. In this tissue, resveratrol increased oxidative capacity. The combination of resveratrol and energy restriction seemingly did not improve the effects induced by the polyphenol alone. Full article
(This article belongs to the Special Issue Benefits of Resveratrol Supplementation)
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Open AccessArticle
Effect of Resveratrol, a Dietary-Derived Polyphenol, on the Oxidative Stress and Polyol Pathway in the Lens of Rats with Streptozotocin-Induced Diabetes
Nutrients 2018, 10(10), 1423; https://doi.org/10.3390/nu10101423
Received: 30 August 2018 / Revised: 16 September 2018 / Accepted: 27 September 2018 / Published: 4 October 2018
Cited by 2 | PDF Full-text (1841 KB) | HTML Full-text | XML Full-text
Abstract
Resveratrol is found in grapes, apples, blueberries, mulberries, peanuts, pistachios, plums and red wine. Resveratrol has been shown to possess antioxidative activity and a variety of preventive effects in models of many diseases. The aim of the study was to investigate if this [...] Read more.
Resveratrol is found in grapes, apples, blueberries, mulberries, peanuts, pistachios, plums and red wine. Resveratrol has been shown to possess antioxidative activity and a variety of preventive effects in models of many diseases. The aim of the study was to investigate if this substance may counteract the oxidative stress and polyol pathway in the lens of diabetic rats. The study was conducted on the rats with streptozotocin-induced type 1 diabetes. After the administration of resveratrol (10 and 20 mg/kg po for 4 weeks), the oxidative stress markers in the lens were evaluated: activity of superoxide dismutase, catalase and glutathione peroxidase, as well as levels of total and soluble protein, level of glutathione, vitamin C, calcium, sulfhydryl group, advanced oxidation protein products, malonyldialdehyde, Total Oxidant Status and Total Antioxidant Reactivity. The obtained results indicate that the administration of resveratrol to the diabetic rats shows antioxidative properties. It is not a result of antiglycaemic activity but resveratrol probably directly affects the antioxidative system. Resveratrol did not affect the polyol pathway in the lens of diabetic rats. Our results may indirectly indicate benefits of consumption of foods as well as dietary supplements containing resveratrol in diminishing oxidative stress in lenses of individuals suffering from diabetes mellitus. Full article
(This article belongs to the Special Issue Benefits of Resveratrol Supplementation)
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Open AccessArticle
The Synergistic Effects of Resveratrol combined with Resistant Training on Exercise Performance and Physiological Adaption
Nutrients 2018, 10(10), 1360; https://doi.org/10.3390/nu10101360
Received: 29 July 2018 / Revised: 6 September 2018 / Accepted: 20 September 2018 / Published: 22 September 2018
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Abstract
The comprehensive studies done on resveratrol (RES) support that this polyphenol has multiple bioactivities and is widely accepted for dietary supplementation. Furthermore, regular exercise is known to have benefits on health and is considered as a form of preventive medicine. Although the vast [...] Read more.
The comprehensive studies done on resveratrol (RES) support that this polyphenol has multiple bioactivities and is widely accepted for dietary supplementation. Furthermore, regular exercise is known to have benefits on health and is considered as a form of preventive medicine. Although the vast majority of prior studies emphasize the efficacy of aerobic exercise in promoting physiological adaptions, other types of exercise, such as resistance exercise and high-intensity interval training (HIIT), may achieve similar or different physiological outcomes. Few studies have looked into the effectiveness of a combinational, synergistic approach to exercise using a weight-loading ladder climbing animal platform. In this study, ICR mice were allocated randomly to the RES and training groups using a two-way ANOVA (RES × Training) design. Exercise capacities, including grip strength, aerobic performance, and anaerobic performance, were assessed and the physiological adaptions were evaluated using fatigue-associated indexes that were implemented immediately after the exercise intervention. In addition, glycogen levels, muscular characteristics, and safety issues, including body composition, histopathology, and biochemistry, were further elucidated. Synergistic effects were observed on grip strength, anaerobic capacities, and exercise lactate, with significant interaction effects. Moreover, the training or RES may have contributed significantly to elevating aerobic capacity, tissue glycogen, and muscle hypertrophy. Toxic and other deleterious effects were also considered to evaluate the safety of the intervention. Resistance exercise in combination with resveratrol supplementation may be applied in the general population to achieve better physiological benefits, promote overall health, and promote participation in regular physical activities. Full article
(This article belongs to the Special Issue Benefits of Resveratrol Supplementation)
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Open AccessArticle
Induction of p53 Phosphorylation at Serine 20 by Resveratrol Is Required to Activate p53 Target Genes, Restoring Apoptosis in MCF-7 Cells Resistant to Cisplatin
Nutrients 2018, 10(9), 1148; https://doi.org/10.3390/nu10091148
Received: 28 July 2018 / Revised: 14 August 2018 / Accepted: 20 August 2018 / Published: 23 August 2018
Cited by 2 | PDF Full-text (2834 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Resistance to cisplatin (CDDP) is a major cause of cancer treatment failure, including human breast cancer. The tumor suppressor protein p53 is a key factor in the induction of cell cycle arrest, DNA repair, and apoptosis in response to cellular stimuli. This protein [...] Read more.
Resistance to cisplatin (CDDP) is a major cause of cancer treatment failure, including human breast cancer. The tumor suppressor protein p53 is a key factor in the induction of cell cycle arrest, DNA repair, and apoptosis in response to cellular stimuli. This protein is phosphorylated in serine 15 and serine 20 during DNA damage repair or in serine 46 to induce apoptosis. Resveratrol (Resv) is a natural compound representing a promising chemosensitizer for cancer treatment that has been shown to sensitize tumor cells through upregulation and phosphorylation of p53 and inhibition of RAD51. We developed a CDDP-resistant MCF-7 cell line variant (MCF-7R) to investigate the effect of Resv in vitro in combination with CDDP over the role of p53 in overcoming CDDP resistance in MCF-7R cells. We have shown that Resv induces sensitivity to CDDP in MCF-7 and MCF-7R cells and that the downregulation of p53 protein expression and inhibition of p53 protein activity enhances resistance to CDDP in both cell lines. On the other hand, we found that Resv induces serine 20 (S20) phosphorylation in chemoresistant cells to activate p53 target genes such as PUMA and BAX, restoring apoptosis. It also changed the ratio between BCL-2 and BAX, where BCL-2 protein expression was decreased and at the same time BAX protein was increased. Interestingly, Resv attenuates CDDP-induced p53 phosphorylation in serine 15 (S15) and serine 46 (S46) probably through dephosphorylation and deactivation of ATM. It also activates different kinases, such as CK1, CHK2, and AMPK to induce phosphorylation of p53 in S20, suggesting a novel mechanism of p53 activation and chemosensitization to CDDP. Full article
(This article belongs to the Special Issue Benefits of Resveratrol Supplementation)
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Open AccessArticle
Gene Expression of Sirtuin-1 and Endogenous Secretory Receptor for Advanced Glycation End Products in Healthy and Slightly Overweight Subjects after Caloric Restriction and Resveratrol Administration
Nutrients 2018, 10(7), 937; https://doi.org/10.3390/nu10070937
Received: 30 June 2018 / Revised: 15 July 2018 / Accepted: 19 July 2018 / Published: 21 July 2018
Cited by 1 | PDF Full-text (597 KB) | HTML Full-text | XML Full-text
Abstract
Sirtuin-1 (Sirt-1) and an endogenous secretory receptor for an advanced glycation end product (esRAGE) are associated with vascular protection. The purpose of this study was to examine the effects of resveratrol (RSV) and caloric restriction (CR) on gene expression of Sirt-1 and esRAGE [...] Read more.
Sirtuin-1 (Sirt-1) and an endogenous secretory receptor for an advanced glycation end product (esRAGE) are associated with vascular protection. The purpose of this study was to examine the effects of resveratrol (RSV) and caloric restriction (CR) on gene expression of Sirt-1 and esRAGE on serum levels of Sirt1 and esRAGE in healthy and slightly overweight subjects. The study included 48 healthy subjects randomized to 30 days of RSV (500 mg/day) or CR (1000 cal/day). Waist circumference (p = 0.011), TC (p = 0.007), HDL (p = 0.031), non-HDL (p = 0.025), ApoA1 (p = 0.011), and ApoB (p = 0.037) decreased in the CR group. However, TC (p = 0.030), non-HDL (p = 0.010), ApoB (p = 0.034), and HOMA-IR (p = 0.038) increased in the RSV group. RSV and CR increased serum levels of Sirt-1, respectively, from 1.06 ± 0.71 ng/mL to 5.75 ± 2.98 ng/mL (p < 0.0001) and from 1.65 ± 1.81 ng/mL to 5.80 ± 2.23 ng/mL (p < 0.0001). esRAGE serum levels were similar in RSV (p = NS) and CR (p = NS) groups. Significant positive correlation was observed between gene expression changes of Sirt-1 and esRAGE in RSV (r = 0.86; p < 0.0001) and in CR (r = 0.71; p < 0.0001) groups, but not for the changes in serum concentrations. CR promoted increases in the gene expression of esRAGE (post/pre). Future long-term studies are needed to evaluate the impact of these outcomes on vascular health. Full article
(This article belongs to the Special Issue Benefits of Resveratrol Supplementation)
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Review

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Open AccessReview
Resveratrol and Its Human Metabolites—Effects on Metabolic Health and Obesity
Nutrients 2019, 11(1), 143; https://doi.org/10.3390/nu11010143
Received: 22 November 2018 / Revised: 6 January 2019 / Accepted: 8 January 2019 / Published: 11 January 2019
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Abstract
Resveratrol is one of the most widely studied polyphenols and it has been assigned a plethora of metabolic effects with potential health benefits. Given its low bioavailability and extensive metabolism, clinical studies using resveratrol have not always replicated in vitro observations. In this [...] Read more.
Resveratrol is one of the most widely studied polyphenols and it has been assigned a plethora of metabolic effects with potential health benefits. Given its low bioavailability and extensive metabolism, clinical studies using resveratrol have not always replicated in vitro observations. In this review, we discuss human metabolism and biotransformation of resveratrol, and reported molecular mechanisms of action, within the context of metabolic health and obesity. Resveratrol has been described as mimicking caloric restriction, leading to improved exercise performance and insulin sensitivity (increasing energy expenditure), as well as having a body fat-lowering effect by inhibiting adipogenesis, and increasing lipid mobilization in adipose tissue. These multi-organ effects place resveratrol as an anti-obesity bioactive of potential therapeutic use. Full article
(This article belongs to the Special Issue Benefits of Resveratrol Supplementation)
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Open AccessReview
Health Effects of Resveratrol: Results from Human Intervention Trials
Nutrients 2018, 10(12), 1892; https://doi.org/10.3390/nu10121892
Received: 30 October 2018 / Revised: 23 November 2018 / Accepted: 27 November 2018 / Published: 3 December 2018
Cited by 4 | PDF Full-text (1149 KB) | HTML Full-text | XML Full-text
Abstract
The effect of resveratrol (RV) intake has been reviewed in several studies performed in humans with different health status. The purpose of this review is to summarize the results of clinical trials of the last decade, in which RV was determined in biological [...] Read more.
The effect of resveratrol (RV) intake has been reviewed in several studies performed in humans with different health status. The purpose of this review is to summarize the results of clinical trials of the last decade, in which RV was determined in biological samples such as human plasma, urine, and feces. The topics covered include RV bioavailability, pharmacokinetics, effects on cardiovascular diseases, cognitive diseases, cancer, type 2 diabetes (T2D), oxidative stress, and inflammation states. The overview of the recent research reveals a clear tendency to identify RV in plasma, showing that its supplementation is safe. Furthermore, RV bioavailability depends on several factors such as dose, associated food matrix, or time of ingestion. Notably, enterohepatic recirculation of RV has been observed, and RV is largely excreted in the urine within the first four hours after consumption. Much of the research on RV in the last 10 years has focused on its effects on pathologies related to oxidative stress, inflammatory biomarkers, T2D, cardiovascular diseases, and neurological diseases. Full article
(This article belongs to the Special Issue Benefits of Resveratrol Supplementation)
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Open AccessReview
Beneficial Effects of Resveratrol Administration—Focus on Potential Biochemical Mechanisms in Cardiovascular Conditions
Nutrients 2018, 10(11), 1813; https://doi.org/10.3390/nu10111813
Received: 15 October 2018 / Revised: 8 November 2018 / Accepted: 14 November 2018 / Published: 21 November 2018
Cited by 4 | PDF Full-text (579 KB) | HTML Full-text | XML Full-text
Abstract
Resveratrol (RV) is a natural non-flavonoid polyphenol and phytoalexin produced by a number of plants such as peanuts, grapes, red wine and berries. Numerous in vitro studies have shown promising results of resveratrol usage as antioxidant, antiplatelet or anti-inflammatory agent. Beneficial effects of [...] Read more.
Resveratrol (RV) is a natural non-flavonoid polyphenol and phytoalexin produced by a number of plants such as peanuts, grapes, red wine and berries. Numerous in vitro studies have shown promising results of resveratrol usage as antioxidant, antiplatelet or anti-inflammatory agent. Beneficial effects of resveratrol activity probably result from its ability to purify the body from ROS (reactive oxygen species), inhibition of COX (cyclooxygenase) and activation of many anti-inflammatory pathways. Administration of the polyphenol has a potential to slow down the development of CVD (cardiovascular disease) by influencing on certain risk factors such as development of diabetes or atherosclerosis. Resveratrol induced an increase in Sirtuin-1 level, which by disrupting the TLR4/NF-κB/STAT signal cascade (toll-like receptor 4/nuclear factor κ-light-chain enhancer of activated B cells/signal transducer and activator of transcription) reduces production of cytokines in activated microglia. Resveratrol caused an attenuation of macrophage/mast cell-derived pro-inflammatory factors such as PAF (platelet-activating factor), TNF-α (tumour necrosis factor-α and histamine. Endothelial and anti-oxidative effect of resveratrol may contribute to better outcomes in stroke management. By increasing BDNF (brain-derived neurotrophic factor) serum concentration and inducing NOS-3 (nitric oxide synthase-3) activity resveratrol may have possible therapeutical effects on cognitive impairments and dementias especially in those characterized by defective cerebrovascular blood flow. Full article
(This article belongs to the Special Issue Benefits of Resveratrol Supplementation)
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Open AccessReview
Resveratrol, Metabolic Syndrome, and Gut Microbiota
Nutrients 2018, 10(11), 1651; https://doi.org/10.3390/nu10111651
Received: 15 October 2018 / Revised: 27 October 2018 / Accepted: 29 October 2018 / Published: 3 November 2018
Cited by 5 | PDF Full-text (702 KB) | HTML Full-text | XML Full-text
Abstract
Resveratrol is a polyphenol which has been shown to have beneficial effects on metabolic syndrome-related alterations in experimental animals, including glucose and lipid homeostasis improvement and a reduction in fat mass, blood pressure, low-grade inflammation, and oxidative stress. Clinical trials have been carried [...] Read more.
Resveratrol is a polyphenol which has been shown to have beneficial effects on metabolic syndrome-related alterations in experimental animals, including glucose and lipid homeostasis improvement and a reduction in fat mass, blood pressure, low-grade inflammation, and oxidative stress. Clinical trials have been carried out to address its potential; however, results are still inconclusive. Even though resveratrol is partly metabolized by gut microbiota, the relevance of this “forgotten organ” had not been widely considered. However, in the past few years, data has emerged suggesting that the therapeutic potential of this compound may be due to its interaction with gut microbiota, reporting changes in bacterial composition associated with beneficial metabolic outcomes. Even though data is still scarce and for the most part observational, it is promising nevertheless, suggesting that resveratrol supplementation could be a useful tool for the treatment of metabolic syndrome and its associated conditions. Full article
(This article belongs to the Special Issue Benefits of Resveratrol Supplementation)
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