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Special Issue "Effects of Resveratrol Supplementation on Human Health and Disease"

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

Deadline for manuscript submissions: closed (15 August 2017)

Special Issue Editor

Guest Editor
Dr. James M. Smoliga

Department of Physical Therapy, High Point University, High Point, North Carolina, USA
Website | E-Mail
Interests: resveratrol; sports medicine; exercise physiology; statistical analysis; clinical translation of basic science; accuracy in scientific reporting

Special Issue Information

Dear Colleagues,

It has been just over a decade since research regarding the health benefits of resveratrol captured the attention of the mainstream community. In 2006, David Sinclair’s laboratory published their findings that resveratrol supplementation improved health and survival of mice fed a high calorie diet. That same year, Baur and Sinclair published an instrumental review paper, which synthesized the available in vivo evidence to demonstrate that resveratrol had unprecedented potential to counter the development and progression of chronic disease, and could perhaps inspire the next class of “wonder drugs”. As news stories and online communities touted the promise of resveratrol, consumers found a health-related justification to drink red wine, while supplement companies found a new product to market. The pharmaceutical industry invested in resveratrol’s clinical promise through attempting to develop and test novel resveratrol formulations and analogues for treating disease in humans.

It is not surprising that clinical trials regarding resveratrol supplementation in humans began to emerge in 2007, with Boocock et al. demonstrating that dosages up to five grams per day were tolerable and safe in healthy humans. In the years since, resveratrol has endured a rollercoaster ride of controversy. Although early clinical trials generally seemed to support the beneficial cardiometabolic effects of a wide range of dosages of resveratrol supplementation, these initial studies were often limited in various ways. The enthusiasm for resveratrol was soon hampered by a few high-profile cases of research fraud, combined with an early termination to a multiple myeloma clinical trial examining a resveratrol formulation. Dozens of clinical trials have been performed since, exploring the effects of a wide range of resveratrol dosages on numerous clinical outcome measures across a diverse array of patient populations from around the world. While some of these results are indeed promising, there are plenty of disappointing results. Explanations for contradictory findings have ranged from criticisms of dosage selection and research methodology, to the notion that resveratrol does is not effective in healthy individuals, or that resveratrol simply does not produce the same physiologic effects in humans that it does in animal models. A number of fundamental questions tangential to clinical trial design have also continued to challenge researchers, such as resveratrol’s exact targets and mechanism(s) of action, the bioactivity of resveratrol’s metabolites, and whether its bioavailability is sufficient for it to have clinical applications.

There is now a wealth of information in the peer-review literature regarding resveratrol, yet the clinical utility of resveratrol remains uncertain. To gain a greater understanding of the effects of resveratrol on human health and disease, articles exploring a wide-range of topics are welcomed in this Special Issue of Nutrients. We welcome original research investing the clinical efficacy of resveratrol in various patient populations and its effects on healthy individuals, as well as synthesis papers that provide novel insights directly relevant to the clinical applications of resveratrol.

Dr. James M. Smoliga, DVM, PhD
Guest Editor

Manuscript Submission Information

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Keywords

  • resveratrol
  • red wine
  • nutraceutical
  • phytochemical
  • stilbene

Published Papers (14 papers)

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Research

Jump to: Review

Open AccessArticle Involvement of UDP-Glucuronosyltransferases and Sulfotransferases in the Excretion and Tissue Distribution of Resveratrol in Mice
Nutrients 2017, 9(12), 1347; https://doi.org/10.3390/nu9121347
Received: 26 October 2017 / Revised: 27 November 2017 / Accepted: 7 December 2017 / Published: 12 December 2017
Cited by 2 | PDF Full-text (1939 KB) | HTML Full-text | XML Full-text
Abstract
Resveratrol is a naturally occurring polyphenolic compound with various pharmacological activities. It is unknown whether the expression of metabolizing enzymes correlates with resveratrol levels in organs and tissues. Therefore, we investigated the metabolism and tissue distribution of resveratrol in mice and assessed its
[...] Read more.
Resveratrol is a naturally occurring polyphenolic compound with various pharmacological activities. It is unknown whether the expression of metabolizing enzymes correlates with resveratrol levels in organs and tissues. Therefore, we investigated the metabolism and tissue distribution of resveratrol in mice and assessed its association with the expression of UDP-glucuronosyltransferase (Ugt) and sulfotransferase (Sult) genes. Plasma, urine, feces, and various organs were analyzed using high-performance liquid chromatography at up to 8 h after intragastric resveratrol administration. The metabolism of resveratrol was pronounced, leading to the formation of resveratrol glucuronides and sulfates. Concentrations of resveratrol and its metabolites were high in the gastrointestinal organs, urine, and feces, but low in the liver and kidneys. In lung, heart, thymus, and brain tissues, parent resveratrol levels exceeded the sulfate and glucuronide concentrations. The formation of resveratrol conjugates correlated with the expression of certain Ugt and Sult genes. Reverse transcription quantitative PCR (RT-qPCR) analysis revealed high mRNA expression of Ugt1a1 and Ugt1a6a in the liver, duodenum, jejunum, ileum, and colon, leading to high concentrations of resveratrol-3-O-glucuronide in these organs. Strong correlations of resveratrol-3-O-sulfate and resveratrol-3-O-4′-O-disulfate formation with Sult1a1 mRNA expression were also observed, particularly in the liver and colon. In summary, our data revealed organ-specific expression of Sults and Ugts in mice that strongly affects resveratrol concentrations; this may also be predictive in humans following oral uptake of dietary resveratrol. Full article
(This article belongs to the Special Issue Effects of Resveratrol Supplementation on Human Health and Disease)
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Open AccessArticle The Effect of Piceatannol from Passion Fruit (Passiflora edulis) Seeds on Metabolic Health in Humans
Nutrients 2017, 9(10), 1142; https://doi.org/10.3390/nu9101142
Received: 29 August 2017 / Revised: 22 September 2017 / Accepted: 12 October 2017 / Published: 18 October 2017
Cited by 2 | PDF Full-text (1375 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Animal studies have shown the beneficial effects of piceatannol on metabolic health; however, there is a lack of human studies designed to examine these effects. The objective of this study was to investigate the effects of piceatannol on metabolic health in humans. This
[...] Read more.
Animal studies have shown the beneficial effects of piceatannol on metabolic health; however, there is a lack of human studies designed to examine these effects. The objective of this study was to investigate the effects of piceatannol on metabolic health in humans. This randomized, placebo-controlled study was conducted on 39 subjects, including 10 overweight men and 9 overweight women (BMI ≥ 25), as well as 10 non-overweight men and 10 non-overweight women (BMI < 25). Subjects received piceatannol (20 mg/day) or placebo capsules for eight weeks in a random order. The primary outcome was the effect of piceatannol on glucose-metabolism, including insulin sensitivity. The secondary outcomes were the effects on other parameters, including blood pressure (BP), heart rate (HR), endothelial function, lipids, inflammation, oxidative stress, mood status, and Sirt1 and phospho-AMP-activated kinase (p-AMPK) expression in isolated peripheral blood mononuclear cells (PBMNCs). Supplementation with piceatannol in overweight men reduced serum insulin levels, HOMA-IR, BP and HR. Other groups, including non-overweight men, as well as overweight and non-overweight women, showed no beneficial effects on insulin sensitivity, BP and HR. Furthermore, piceatannol is not associated with other data, including body weight (BW), body composition, endothelial function, lipids, inflammation, oxidative stress, mood status, and Sirt1/p-AMPK expression in PBMNCs. In conclusion, supplementation with piceatannol can improve metabolic health, including insulin sensitivity, BP and HR, in overweight men. Full article
(This article belongs to the Special Issue Effects of Resveratrol Supplementation on Human Health and Disease)
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Open AccessArticle Resveratrol Regulates Colorectal Cancer Cell Invasion by Modulation of Focal Adhesion Molecules
Nutrients 2017, 9(10), 1073; https://doi.org/10.3390/nu9101073
Received: 7 August 2017 / Revised: 8 September 2017 / Accepted: 18 September 2017 / Published: 27 September 2017
Cited by 3 | PDF Full-text (5495 KB) | HTML Full-text | XML Full-text
Abstract
Resveratrol, a safe and multi-targeted agent, has been associated with suppression of survival, proliferation and metastasis of cancer, however, the underlying mechanisms for its anti-cancer activity, particularly on cellular signaling during cancer cell migration still remain poorly understood. We investigated the invasion response
[...] Read more.
Resveratrol, a safe and multi-targeted agent, has been associated with suppression of survival, proliferation and metastasis of cancer, however, the underlying mechanisms for its anti-cancer activity, particularly on cellular signaling during cancer cell migration still remain poorly understood. We investigated the invasion response of two human colorectal cancer (CRC) cells (HCT116 and SW480) to resveratrol and studied the effect of specific pharmacological inhibitors, cytochalasin D (CytD) and focal adhesion kinase-inhibitor (FAK-I) on FAK, cell viability and migration in CRC. We found that resveratrol altered cell phenotype of both CRC cells, reduced cell viability and the results were comparable to FAK-I and CytD. These effects of resveratrol were associated with marked Sirt1 up-regulation, FAK down-regulation, inhibition of focal adhesion and potentiation of effects by combinatorial treatment of resveratrol and inhibitors. Interestingly, inhibition of FAK with FAK-I or treatment with CytD suppressed resveratrol-induced Sirt1 up-regulation and markedly down-regulated FAK expression. Resveratrol or combination treatment with inhibitors significantly activated caspase-3 and potentiated apoptosis. Moreover, resveratrol suppressed invasion and colony forming capacity, cell proliferation, β1-Integrin expression and activation of FAK of cells in alginate tumor microenvironment, similar to FAK-I or CytD. Finally, we demonstrated that resveratrol, FAK-I or CytD inhibited activation of NF-κB, suppressed NF-κB-dependent gene end-products involved in invasion, metastasis, and apoptosis; and these effects of resveratrol were potentiated by combination treatment with FAK-I or CytD. Our data illustrated that the anti-invasion effect of resveratrol by inhibition of FAK activity has a potential beneficial role in disease prevention and therapeutic management of CRC. Full article
(This article belongs to the Special Issue Effects of Resveratrol Supplementation on Human Health and Disease)
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Open AccessArticle Resveratrol as a Natural Autophagy Regulator for Prevention and Treatment of Alzheimer’s Disease
Nutrients 2017, 9(9), 927; https://doi.org/10.3390/nu9090927
Received: 26 June 2017 / Revised: 3 August 2017 / Accepted: 11 August 2017 / Published: 24 August 2017
Cited by 3 | PDF Full-text (647 KB) | HTML Full-text | XML Full-text
Abstract
Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders over the age of 65 years old. Although several underlying mechanisms for explaining the pathogenesis of AD are elucidated, the effective supplements or drugs for the intervention of AD are still limited.
[...] Read more.
Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders over the age of 65 years old. Although several underlying mechanisms for explaining the pathogenesis of AD are elucidated, the effective supplements or drugs for the intervention of AD are still limited. Recently, impaired autophagy associated with miRNA dysfunction has been reported to involve in aging and aging-related neurodegenerative diseases. Thus, the activation of autophagy through effectively regulating miRNAs may become a potential target for the prevention or treatment of AD. Mounting evidence from in vitro and in vivo AD models has demonstrated that resveratrol, one of polyphenolic compounds, can exert neuroprotective role in neurodegenerative diseases especially AD. In this review, the regulation of miRNAs and autophagy using resveratrol during the prevention and treatment of AD are systematically discussed, which will be beneficial to establish a target for the direct link between pharmacological intervention and AD in the future. Full article
(This article belongs to the Special Issue Effects of Resveratrol Supplementation on Human Health and Disease)
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Open AccessArticle Resveratrol in Hepatitis C Patients Treated with Pegylated-Interferon-α-2b and Ribavirin Reduces Sleep Disturbance
Nutrients 2017, 9(8), 897; https://doi.org/10.3390/nu9080897
Received: 24 July 2017 / Revised: 7 August 2017 / Accepted: 15 August 2017 / Published: 18 August 2017
Cited by 4 | PDF Full-text (910 KB) | HTML Full-text | XML Full-text
Abstract
Background: Hepatitis C virus infection and interferon treatment have shown to be risk factors for sleep disorder health-related quality of life. Aim: To determine whether the effects of resveratrol on sleep disorders were associated with different tests in subjects with chronic hepatitis C
[...] Read more.
Background: Hepatitis C virus infection and interferon treatment have shown to be risk factors for sleep disorder health-related quality of life. Aim: To determine whether the effects of resveratrol on sleep disorders were associated with different tests in subjects with chronic hepatitis C treated with Peg-IFN-α and RBV. Patients and Methods: In this prospective, randomized, placebo controlled, double blind clinical trial, 30 subjects (Group A) with chronic hepatitis received Pegylated-Interferon-α2b (1.5 mg/kg per week), Ribavirin and placebo (N-acetylcysteine 600 mg and lactoferrin 23.6 g), while 30 subjects (Group B) received the same dosage of Pegylated-Interferon-α2b, Ribavirin and association of N-acetylcysteine 600 mg, lactoferrin 23.6 g and Resveratrol 19.8 mg for 12 months. All subjects underwent laboratory exams and questionnaires to evaluate mood and sleep disorders (General Health Questionnaire (GHQ), Profile of Mood States (POMS), Pittsburgh Sleep Quality Inventory (PSQI), Epworth Sleepiness Scale (ESS)). Results: The comparison between Group A and Group B showed significant differences after six months in C-reactive protein (p < 0.0001); after 12 months in aspartate aminotransferase (AST) (p < 0.0001) Viremia (p < 0.0001), HAI (p < 0.0012) and C-reactive protein (p < 0.0001); and at follow up in AST (p < 0.0001), Viremia (p < 0.0026) and C-reactive protein (p < 0.0001). Significant differences were observed after 12 month and follow-up in General Health Questionnaire, after 1, 6, 12 and follow-up in Profile of Mood States, after 6, 12, follow-up in Pittsburgh Sleep Quality Inventory and Epworth Sleepiness Scale. Conclusions: Supplementation with Resveratrol decreased General Health Questionnaire score and reduced sleep disorders in patients treated with Peg–IFN-α and RBV. Full article
(This article belongs to the Special Issue Effects of Resveratrol Supplementation on Human Health and Disease)
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Open AccessArticle Trans-Resveratrol Supplementation and Endothelial Function during the Fasting and Postprandial Phase: A Randomized Placebo-Controlled Trial in Overweight and Slightly Obese Participants
Nutrients 2017, 9(6), 596; https://doi.org/10.3390/nu9060596
Received: 22 March 2017 / Revised: 1 June 2017 / Accepted: 8 June 2017 / Published: 12 June 2017
Cited by 1 | PDF Full-text (767 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Studies on the effects of the long-term intake of trans-resveratrol on vascular function are conflicting. In addition, postprandial effects of long-term trans-resveratrol intake on endothelial function are not known. We therefore supplemented 45 overweight and slightly obese volunteers (25 men and
[...] Read more.
Studies on the effects of the long-term intake of trans-resveratrol on vascular function are conflicting. In addition, postprandial effects of long-term trans-resveratrol intake on endothelial function are not known. We therefore supplemented 45 overweight and slightly obese volunteers (25 men and 20 women) with a mean (±SD) age of 61 ± 7 years and body mass index of 28.3 ± 3.2 kg/m2 in random order trans-resveratrol (2 × 75 mg/day) or placebo capsules for 4 weeks, separated by a washout period of at least 4 weeks. At the end of each intervention period, brachial artery flow-mediated vasodilation (FMD) was measured before and after meal consumption. Plasma biomarkers for endothelial function, inflammation, and glucose and lipid metabolism were also determined. Compared with the placebo, trans-resveratrol did not affect fasting FMD (2.9 ± 1.4% vs. 3.0 ± 1.9%; p = 0.69). After the postprandial test, changes in FMD (−0.7 ± 2.3% vs. 0.2 ± 2.6%; p = 0.13) were also not significantly different. Postprandial changes in biomarkers were also comparable. In conclusion, for overweight and slightly obese volunteers, a daily intake of 150 mg of trans-resveratrol for 4 weeks does not change plasma biomarkers of endothelial function or inflammation in the fasting state or postprandial phase. Full article
(This article belongs to the Special Issue Effects of Resveratrol Supplementation on Human Health and Disease)
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Review

Jump to: Research

Open AccessReview Resveratrol Role in Autoimmune Disease—A Mini-Review
Nutrients 2017, 9(12), 1306; https://doi.org/10.3390/nu9121306
Received: 16 August 2017 / Revised: 20 September 2017 / Accepted: 20 October 2017 / Published: 1 December 2017
Cited by 5 | PDF Full-text (3634 KB) | HTML Full-text | XML Full-text
Abstract
Autoimmune diseases are still considered to be pressing concerns due the fact that they are leaders in death and disability causes worldwide. Resveratrol is a polyphenol derived from a variety of foods and beverages, including red grapes and red wine. Anti-inflammatory, antioxidant, and
[...] Read more.
Autoimmune diseases are still considered to be pressing concerns due the fact that they are leaders in death and disability causes worldwide. Resveratrol is a polyphenol derived from a variety of foods and beverages, including red grapes and red wine. Anti-inflammatory, antioxidant, and antiaging properties of resveratrol have been reported, and in some animal and human studies this compound reduced and ameliorated the progression of autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, psoriasis, inflammatory bowel disease, and type 1 diabetes mellitus. Thus, this review aims to summarize and critically analyze the role of resveratrol in the modulation of several organ-specific or systemic autoimmune diseases. Full article
(This article belongs to the Special Issue Effects of Resveratrol Supplementation on Human Health and Disease)
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Open AccessReview Effects of Resveratrol against Lung Cancer: In Vitro and In Vivo Studies
Nutrients 2017, 9(11), 1231; https://doi.org/10.3390/nu9111231
Received: 17 October 2017 / Revised: 4 November 2017 / Accepted: 7 November 2017 / Published: 10 November 2017
Cited by 1 | PDF Full-text (250 KB) | HTML Full-text | XML Full-text
Abstract
Uncontrolled cell growth and resistance to apoptosis characterize cancer cells. These two main features are initiated in cancer cells through mutations in key signaling molecules, which regulate pathways that are directly involved in controlling cell proliferation and apoptosis. Resveratrol (RSV), a naturally occurring
[...] Read more.
Uncontrolled cell growth and resistance to apoptosis characterize cancer cells. These two main features are initiated in cancer cells through mutations in key signaling molecules, which regulate pathways that are directly involved in controlling cell proliferation and apoptosis. Resveratrol (RSV), a naturally occurring plant polyphenol, has been shown to have biological effects counteracting different diseases. It has been found to provide cardio-protective, neuro-protective, immuno-modulatory, and anti-cancer health benefits. RSV has been found to inhibit cancer cell proliferation, induce cell cycle arrest and apoptosis, and these anticancer effects may be due to its ability to modulate signaling molecules involved in these processes. The present review summarizes the existing in vitro and in vivo studies on resveratrol and its anti-lung cancer properties. Full article
(This article belongs to the Special Issue Effects of Resveratrol Supplementation on Human Health and Disease)
Open AccessReview Epigenetic Regulatory Mechanisms Induced by Resveratrol
Nutrients 2017, 9(11), 1201; https://doi.org/10.3390/nu9111201
Received: 11 August 2017 / Revised: 5 September 2017 / Accepted: 18 September 2017 / Published: 1 November 2017
Cited by 4 | PDF Full-text (347 KB) | HTML Full-text | XML Full-text
Abstract
Resveratrol (RVT) is one of the main natural compounds studied worldwide due to its potential therapeutic use in the treatment of many diseases, including cancer, diabetes, cardiovascular diseases, neurodegenerative diseases and metabolic disorders. Nevertheless, the mechanism of action of RVT in all of
[...] Read more.
Resveratrol (RVT) is one of the main natural compounds studied worldwide due to its potential therapeutic use in the treatment of many diseases, including cancer, diabetes, cardiovascular diseases, neurodegenerative diseases and metabolic disorders. Nevertheless, the mechanism of action of RVT in all of these conditions is not completely understood, as it can modify not only biochemical pathways but also epigenetic mechanisms. In this paper, we analyze the biological activities exhibited by RVT with a focus on the epigenetic mechanisms, especially those related to DNA methyltransferase (DNMT), histone deacetylase (HDAC) and lysine-specific demethylase-1 (LSD1). Full article
(This article belongs to the Special Issue Effects of Resveratrol Supplementation on Human Health and Disease)
Open AccessReview Red Wine, Resveratrol and Atrial Fibrillation
Nutrients 2017, 9(11), 1190; https://doi.org/10.3390/nu9111190
Received: 15 August 2017 / Revised: 16 October 2017 / Accepted: 21 October 2017 / Published: 30 October 2017
Cited by 1 | PDF Full-text (229 KB) | HTML Full-text | XML Full-text
Abstract
Atrial fibrillation (AF) is a common cardiac arrhythmia that is associated with increased risk for cardiovascular disease and overall mortality. Excessive alcohol intake is a well-known risk factor for AF, but this correlation is less clear with light and moderate drinking. Besides, low
[...] Read more.
Atrial fibrillation (AF) is a common cardiac arrhythmia that is associated with increased risk for cardiovascular disease and overall mortality. Excessive alcohol intake is a well-known risk factor for AF, but this correlation is less clear with light and moderate drinking. Besides, low doses of red wine may acutely prolong repolarization and slow cardiac conduction. Resveratrol, a bioactive polyphenol found in grapes and red wine, has been linked to antiarrhythmic properties and may act as an inhibitor of both intracellular calcium release and pathological signaling cascades in AF, eliminating calcium overload and preserving the cardiomyocyte contractile function. However, there are still no clinical trials at all that prove that resveratrol supplementation leads to improved outcomes. Besides, no observational study supports a beneficial effect of light or moderate alcohol intake and a lower risk of AF. The purpose of this review is to briefly describe possible beneficial effects of red wine and resveratrol in AF, and also present studies conducted in humans regarding chronic red wine consumption, resveratrol, and AF. Full article
(This article belongs to the Special Issue Effects of Resveratrol Supplementation on Human Health and Disease)
Open AccessReview Therapeutic Versatility of Resveratrol Derivatives
Nutrients 2017, 9(11), 1188; https://doi.org/10.3390/nu9111188
Received: 15 August 2017 / Revised: 26 September 2017 / Accepted: 25 October 2017 / Published: 29 October 2017
Cited by 5 | PDF Full-text (998 KB) | HTML Full-text | XML Full-text
Abstract
Resveratrol, a natural phytoalexin, exhibits a remarkable range of biological activities, such as anticancer, cardioprotective, neuroprotective and antioxidant properties. However, the therapeutic application of resveratrol was encumbered for its low bioavailability. Therefore, many researchers focused on designing and synthesizing the derivatives of resveratrol
[...] Read more.
Resveratrol, a natural phytoalexin, exhibits a remarkable range of biological activities, such as anticancer, cardioprotective, neuroprotective and antioxidant properties. However, the therapeutic application of resveratrol was encumbered for its low bioavailability. Therefore, many researchers focused on designing and synthesizing the derivatives of resveratrol to enhance the bioavailability and the pharmacological activity of resveratrol. During the past decades, a large number of natural and synthetic resveratrol derivatives were extensively studied, and the methoxylated, hydroxylated and halogenated derivatives of resveratrol received particular more attention for their beneficial bioactivity. So, in this review, we will summarize the chemical structure and the therapeutic versatility of resveratrol derivatives, and thus provide the related structure activity relationship reference for their practical applications. Full article
(This article belongs to the Special Issue Effects of Resveratrol Supplementation on Human Health and Disease)
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Open AccessReview Resveratrol and Amyloid-Beta: Mechanistic Insights
Nutrients 2017, 9(10), 1122; https://doi.org/10.3390/nu9101122
Received: 19 August 2017 / Revised: 25 September 2017 / Accepted: 2 October 2017 / Published: 14 October 2017
Cited by 9 | PDF Full-text (891 KB) | HTML Full-text | XML Full-text
Abstract
The amyloid-beta (Aβ) hypothesis that dyshomeostasis between Aβ production and clearance is a very early, key molecular factor in the etiology of Alzheimer’s disease (AD) has been proposed and examined in the AD research field. Scientists have focused on seeking natural products or
[...] Read more.
The amyloid-beta (Aβ) hypothesis that dyshomeostasis between Aβ production and clearance is a very early, key molecular factor in the etiology of Alzheimer’s disease (AD) has been proposed and examined in the AD research field. Scientists have focused on seeking natural products or drugs to influence the dynamic equilibrium of Aβ, targeting production and clearance of Aβ. There is emerging evidence that resveratrol (Res), a naturally occurring polyphenol mainly found in grapes and red wine, acts on AD in numerous in vivo and in vitro models. Res decreases the amyloidogenic cleavage of the amyloid precursor protein (APP), enhances clearance of amyloid beta-peptides, and reduces Aβ aggregation. Moreover, Res also protects neuronal functions through its antioxidant properties. This review discusses the action of Res on Aβ production, clearance and aggregation and multiple potential mechanisms, providing evidence of the useful of Res for AD treatment. Full article
(This article belongs to the Special Issue Effects of Resveratrol Supplementation on Human Health and Disease)
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Open AccessReview Dosis Facit Sanitatem—Concentration-Dependent Effects of Resveratrol on Mitochondria
Nutrients 2017, 9(10), 1117; https://doi.org/10.3390/nu9101117
Received: 10 August 2017 / Revised: 20 September 2017 / Accepted: 7 October 2017 / Published: 13 October 2017
Cited by 3 | PDF Full-text (562 KB) | HTML Full-text | XML Full-text
Abstract
The naturally occurring polyphenol, resveratrol (RSV), is known for a broad range of actions. These include a positive impact on lifespan and health, but also pro-apoptotic anti-cancer properties. Interestingly, cell culture experiments have revealed a strong impact of RSV on mitochondrial function. The
[...] Read more.
The naturally occurring polyphenol, resveratrol (RSV), is known for a broad range of actions. These include a positive impact on lifespan and health, but also pro-apoptotic anti-cancer properties. Interestingly, cell culture experiments have revealed a strong impact of RSV on mitochondrial function. The compound was demonstrated to affect mitochondrial respiration, structure and mass of mitochondria as well as mitochondrial membrane potential and, ultimately, mitochondria-associated cell death pathways. Notably, the mitochondrial effects of RSV show a very strict and remarkable concentration dependency: At low concentrations, RSV (<50 μM) fosters cellular antioxidant defense mechanisms, activates AMP-activated protein kinase (AMPK)- and sirtuin 1 (SIRT1)-linked pathways and enhances mitochondrial network formation. These mechanisms crucially contribute to the cytoprotective effects of RSV against toxins and disease-related damage, in vitro and in vivo. However, at higher concentrations, RSV (>50 μM) triggers changes in (sub-)cellular Ca2+ homeostasis, disruption of mitochondrial membrane potential and activation of caspases selectively yielding apoptotic cancer cell death, in vitro and in vivo. In this review, we discuss the promising therapeutic potential of RSV, which is most probably related to the compound’s concentration-dependent manipulation of mitochondrial function and structure. Full article
(This article belongs to the Special Issue Effects of Resveratrol Supplementation on Human Health and Disease)
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Open AccessReview A Critical Assessment of the Therapeutic Potential of Resveratrol Supplements for Treating Mitochondrial Disorders
Nutrients 2017, 9(9), 1017; https://doi.org/10.3390/nu9091017
Received: 8 August 2017 / Revised: 1 September 2017 / Accepted: 11 September 2017 / Published: 14 September 2017
PDF Full-text (932 KB) | HTML Full-text | XML Full-text
Abstract
In human cells, mitochondria provide the largest part of cellular energy in the form of adenosine triphosphate generated by the process of oxidative phosphorylation (OXPHOS). Impaired OXPHOS activity leads to a heterogeneous group of inherited diseases for which therapeutic options today remain very
[...] Read more.
In human cells, mitochondria provide the largest part of cellular energy in the form of adenosine triphosphate generated by the process of oxidative phosphorylation (OXPHOS). Impaired OXPHOS activity leads to a heterogeneous group of inherited diseases for which therapeutic options today remain very limited. Potential innovative strategies aim to ameliorate mitochondrial function by increasing the total mitochondrial load of tissues and/or to scavenge the excess of reactive oxygen species generated by OXPHOS malfunctioning. In this respect, resveratrol, a compound that conveniently combines mitogenetic with antioxidant activities and, as a bonus, possesses anti-apoptotic properties, has come forward as a promising nutraceutical. We review the scientific evidence gathered so far through experiments in both in vitro and in vivo systems, evaluating the therapeutic effect that resveratrol is expected to generate in mitochondrial patients. The obtained results are encouraging, but clearly show that achieving normalization of OXPHOS function with this strategy alone could prove to be an unattainable goal. Full article
(This article belongs to the Special Issue Effects of Resveratrol Supplementation on Human Health and Disease)
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