stilbenes and Cardiovascular-Diseases

Resveratrol is a natural polyphenolic compound with a stilbene structure endowed with multiple health-promoting effects. Among phenolic compounds, resveratrol is assigned a leading role in the health-promoting effects of red wine.. The aim of the study was to assess the effect of resveratrol on the cardiovascular system in the experimental and clinical studies conducted so far. Moreover, the paper discusses the results of the most recent meta-analyses assessing resveratrol's therapeutic effect on the cardiovascular system in humans.. In animal and preclinical studies, resveratrol has demonstrated a wide physiological and biochemical spectrum of activity, including antioxidant, anti-inflammatory, antiplatelet, and anticoagulant activities, which translated into its health-promoting effects on the cardiovascular system. The performed meta-analyses allow to confirm such an impact, however, after the assessment with the use of the SYRCLE's tool, these studies are burdened with a high risk of bias, and the results are not clearly presented.. Despite numerous articles and clinical studies, the convincing beneficial mechanisms of resveratrol as well as its health-promoting effects in cardiovascular diseases have not been clearly confirmed in humans. Therefore, there is a need for further clinical studies, especially randomized, double-blind, placebo-controlled trials to objectively confirm the possible health-promoting effects of this substance and to determine both the efficacy and safety, and possible therapeutic potential.

Topics: Animals; Antioxidants; Cardiovascular Diseases; Cardiovascular System; Humans; Randomized Controlled Trials as Topic; Resveratrol; Stilbenes

Pterostilbene, 3',5'-dimethoxy-4-hydroxystilbene, is a resveratrol analogue and has been reported to have similar and often potent health-promoting properties. Pterostilbene has been shown to reduce weight gain, liver fat, plasma cholesterol, adiposity, inflammatory biomarkers, blood glucose, and other physiological characteristics of metabolic diseases in animal models. Studies on pterostilbene suggest that it may improve risk factors associated with diabetes, cardiovascular disease, fatty liver diseases, Alzheimer's disease, and other neurodegenerative diseases. Many of the extensive studies on the potential health benefits of pterostilbene were conducted by Dr. Agnes Rimando, a scientist with the United States Department of Agriculture, in collaboration with many U.S. and other international research groups. This review highlights the pterostilbene research of Dr. Rimando.

Topics: Alzheimer Disease; Animals; Antioxidants; Cardiovascular Diseases; Humans; Obesity; Stilbenes

Stilbenoids are a group of naturally occurring phenolic compounds found in various plant species. They share a common backbone structure known as stilbene. However, differences in the nature and position of substituents have made it possible to produce many derivatives. Piceatannol [PT], a hydroxylated derivative from resveratrol, exerts various biological activities ranging from cancer prevention, cardio- protection, neuro-protection, anti-diabetic, depigmentation and so on. Although positive results were obtained in most cell culture and animal studies, the relevant cellular and molecular mechanisms of cytokines and signaling pathway about their biological effects still unclear. Thus, in the current review, we focus on the latest findings of PT on cellular biology in order to better understand the underlying therapeutic mechanisms of PT among various diseases.

Topics: Animals; Cardiovascular Diseases; Cell Cycle; Fabaceae; Humans; Neoplasms; Neuroprotection; Phytotherapy; Protein Kinase Inhibitors; Resveratrol; Signal Transduction; Stilbenes

Over the past years, several studies have found that foods rich in polyphenols protect against age-related disease, such as atherosclerosis, cardiovascular disease, cancer, arthritis, cataracts, osteoporosis, type 2 diabetes (T2D), hypertension and Alzheimer's disease. Resveratrol and pterostilbene, the polyphenol found in grape and blueberries, have beneficial effects as anti-aging compounds through modulating the hallmarks of aging, including oxidative damage, inflammation, telomere attrition and cell senescence. In this review, we discuss the relationship between resveratrol and pterostilbene and possible aging biomarker, including oxidative stress, inflammation, and high-calorie diets. Moreover, we also discuss the positive effect of resveratrol and pterostilbene on lifespan, aged-related disease, and health maintenance. Furthermore, we summarize a variety of important mechanisms modulated by resveratrol and pterostilbene possibly involved in attenuating age-associated disorders. Overall, we describe resveratrol and pterostilbene potential for prevention or treatment of several age-related diseases by modulating age-related mechanisms. © 2017 BioFactors, 44(1):69-82, 2018.

Topics: AMP-Activated Protein Kinases; Animals; Antioxidants; Cardiovascular Diseases; Cataract; Cellular Senescence; Humans; Inflammation; Longevity; Neoplasms; Neurodegenerative Diseases; NF-E2-Related Factor 2; Osteoporosis; Oxidative Stress; Resveratrol; Sirtuin 1; Stilbenes; Telomere Homeostasis

Epigenetic mechanisms are essential in regulating normal cellular functions and play an important role during the disease developmental stages. However, aberrant epigenetic mechanisms may lead to pathological consequences such as cancer, neurological disorders, bone and skeletal diseases, cardiovascular dysfunction, and metabolic syndrome. The molecular mechanisms of epigenetic modification include DNA methylation, histone modification (acetylation, methylation and phosphorylation), and microRNAs (miRNAs). Unlike genetic modifications, epigenetic states of genes are reversible and can be altered by certain intrinsic and extrinsic factors. In the past few decades, accumulated evidence shows that dietary phytochemicals with chemopreventive effects are also potent epigenetic regulators. Resveratrol and pterostilbene are stilbenoids, which have been reported to have anti-cancer, anti-inflammatory, anti-lipid, and anti-diabetic properties. Stilbenoids are also reported to improve cardiovascular disease. By altering DNA methylation and histone modification or by modulating miRNA expression, resveratrol, and pterostilbene become potent epigenetic modifiers. In this review, we summarize these studies and underlying mechanisms of resveratrol and pterostilbene and their influence on epigenetic mechanisms. © 2017 BioFactors, 44(1):26-35, 2018.

Topics: Anti-Inflammatory Agents; Anticarcinogenic Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Bone Diseases; Cardiovascular Diseases; Chemoprevention; DNA Methylation; Epigenesis, Genetic; Histones; Humans; MicroRNAs; Neoplasms; Neurodegenerative Diseases; Protein Processing, Post-Translational; Resveratrol; Stilbenes

Functional foods describe the importance of foods in promoting health and preventing diseases aside their primary role of providing the body with the required amount of essential nutrients such as proteins, carbohydrates, vitamins, fats, and oils needed for its healthy survival. This review explains the interaction of functional food bioactive compounds including polyphenols (phenolic acids [hydroxybenzoic acids and hydroxycinnamic acids], flavonoids [flavonols, flavones, flavanols, flavanones, isoflavones, proanthocyanidins], stilbenes, and lignans), terpenoids, carotenoids, alkaloids, omega-3 and polyunsaturated fatty acids, among others with critical enzymes (α- amylase, α- glucosidase, angiotensin-I converting enzyme [ACE], acetylcholinesterase [AChE], and arginase) linked to some degenerative diseases (type-2 diabetes, cardiovascular diseases [hypertension], neurodegenerative diseases [Alzheimer's disease] and erectile dysfunction). Different functional food bioactive compounds may synergistically/additively confer an overwhelming protection against these degenerative diseases by modulating/altering the activities of these critical enzymes of physiological importance.

Topics: Alkaloids; Cardiovascular Diseases; Carotenoids; Chronic Disease; Diabetes Mellitus, Type 2; Dietary Supplements; Erectile Dysfunction; Flavonoids; Functional Food; Health Promotion; Humans; Lignans; Male; Neurodegenerative Diseases; Nutritional Requirements; Phenols; Polyphenols; Stilbenes

Inflammation is the principal response invoked by the body to address injuries. Despite inflammation constituting a crucial component of tissue repair, it is well known that unchecked or chronic inflammation becomes deleterious, leading to progressive tissue damage. Studies over the past years focused on foods rich in polyphenols with anti-inflammatory and immunomodulatory properties, since inflammation was recognized to play a central role in several diseases. In this review, we discuss the beneficial effects of resveratrol, the most widely investigated polyphenol, on cancer and neurodegenerative, respiratory, metabolic, and cardiovascular diseases. We highlight how resveratrol, despite its unfavorable pharmacokinetics, can modulate the inflammatory pathways underlying those diseases, and we identify future opportunities for the evaluation of its clinical feasibility.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cardiovascular Diseases; Clinical Trials as Topic; Humans; Inflammation; Mice; Neoplasms; Obesity; Rats; Respiratory Tract Diseases; Resveratrol; Stilbenes

From ancient times, natural products have been continuously used as therapeutic agents in the treatment of various ailments. Many drugs from the natural origin are available in the market as potent medicines. Over expression of cyclooxygenase-2 (COX-2) enzyme is associated with various physical disorders like various types of inflammations associated with cardiovascular diseases or malignancies. The COX-2 inhibitory activity of many active constituents derived from plants is well established in the literature. These include coumarins, alkaloids, flavonoids, cinnamates, stilbenes and xanthines. In the present review, an attempt has been made to summarize applications of compounds since 2000 obtained from natural sources as COX-2 inhibitors. A brief synthetic methodology to access these natural product derivatives has been highlighted along with the Structure Activity Relationship (SAR).

Topics: Alkaloids; Biological Products; Cardiovascular Diseases; Cinnamates; Coumarins; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Drug Discovery; Flavonoids; Humans; Molecular Structure; Neoplasms; Stilbenes; Structure-Activity Relationship

Resveratrol is a naturally occurring phenol that is generated by plant species following injury or attack by bacterial and fungal pathogens. This compound was first described as the French Paradox in 1992. Later in 2003, resveratrol was reported to activate sirtuins in yeast cells. Recent experimental studies have found that resveratrol offers a variety of benefits that include both anticarcinogenic and anti-inflammatory effects in addition to the ability to reverse obesity, attenuate hyperglycemia and hyperinsulinemia, protect heart and endothelial function, and increase the life span. Multiple molecular targets are associated with the cardioprotective capabilities of resveratrol, and therefore, resveratrol has potential for a wide range of new therapeutic strategies for atherosclerosis, ischemia/reperfusion, metabolic syndrome, cardiac failure, and inflammatory alterations during aging. Expectations for application in human patients, however, suffer from a lack of sufficient clinical evidence in support of these beneficial effects. This article reviews recently reported basic research results that describe the beneficial effects of resveratrol in an attempt to condense the evidence observed in clinical trials and provide support for the future development of novel clinical therapeutics in patients with cardiovascular diseases.

Topics: Animals; Anti-Inflammatory Agents; Antihypertensive Agents; Cardiotonic Agents; Cardiovascular Diseases; Humans; Hypolipidemic Agents; Phenols; Plant Extracts; Randomized Controlled Trials as Topic; Resveratrol; Stilbenes

Natural products or nutraceuticals promote anti-aging, anti-cancer and other health-enhancing effects. A key target of the effects of natural products may be the regulation of the PI3K/PTEN/Akt/mTORC1/GSK-3 pathway. This review will focus on the effects of curcumin (CUR), berberine (BBR) and resveratrol (RES), on the PI3K/PTEN/Akt/mTORC1/GSK-3 pathway, with a special focus on GSK-3. These natural products may regulate the pathway by multiple mechanisms including: reactive oxygen species (ROS), cytokine receptors, mirco-RNAs (miRs) and many others. CUR is present the root of turmeric (Curcuma longa). CUR is used in the treatment of many disorders, especially in those involving inflammatory processes which may contribute to abnormal proliferation and promote cancer growth. BBR is also isolated from various plants (Berberis coptis and others) and is used in traditional medicine to treat multiple diseases/conditions including: diabetes, hyperlipidemia, cancer and bacterial infections. RES is present in red grapes, other fruits and berries such as blueberries and raspberries. RES may have some anti-diabetic and anti-cancer effects. Understanding the effects of these natural products on the PI3K/PTEN/Akt/mTORC1/GSK-3 pathway may enhance their usage as anti-proliferative agent which may be beneficial for many health problems.

Topics: Berberine; Cardiovascular Diseases; Curcumin; Gene Expression Regulation; Glycogen Synthase Kinase 3; Humans; Inflammation; Mechanistic Target of Rapamycin Complex 1; Neoplasms; Neurodegenerative Diseases; Osteoarthritis; Phosphatidylinositol 3-Kinases; Protective Agents; Proto-Oncogene Proteins c-akt; PTEN Phosphohydrolase; Resveratrol; Signal Transduction; Stilbenes

Resveratrol could be beneficial to health and provides protection against a wide array of pathologies and age-associated problems, as evident from preclinical studies. However, a comparison of animal and human studies reveals that this dietary polyphenol cannot protect against metabolic diseases and their associated complications. The clinical outcomes are affected by many factors such as sample size. This article not only presents a comprehensive review of the current advances concerning the dose, the extent of absorption, interaction and toxicity of resveratrol in human studies, but also describes its therapeutic effects against several chronic diseases such as diabetes mellitus, obesity, cardiovascular diseases, cancer and aging and the related diseases.

Topics: Aging; Cardiovascular Diseases; Chronic Disease; Diabetes Mellitus; Dose-Response Relationship, Drug; Humans; Neoplasms; Obesity; Polyphenols; Resveratrol; Stilbenes

The stilbene derivative resveratrol (3,5,4'-trihydroxy-stilbene; RESV) has become the subject of interest of many researchers and the pharmaceutical industries due to its well-acclaimed beneficial biological activities. Although earlier research tended to focus on the effects of RESV on cardiovascular disorders, many other studies have described the beneficial effects of RESV in the areas of cancer chemoprevention and inflammation and interest of researchers on this compound is still increasing. It is now well accepted that the effect of RESV is not just due to its so called "antioxidant" activity but mainly (if not only) because of the ability of this compound to trigger cell signaling pathways and gene expression involved in cellular defense systems. Many "in vitro" studies on RESV did not take into account that although its oral absorption is about 75% it undergoes rapid metabolism and the concentration in the blood stream is almost undetectable. For this reason interest in the topical usage of RESV by cosmeceutical skin care brands has exponentially increased in the last decade reporting in general very promising results on its beneficial effect in protecting the skin from outdoor insults, but there is still some controversy on its topical usage mainly surrounding the concentration used. Therefore, more basic research on the topical application of RESV should be performed to better understand the way it prevents cutaneous damage and whether it could be recommended as a preventive skin aging agent for all skin insults.

Topics: Animals; Cardiovascular Diseases; Cosmetics; Humans; Resveratrol; Skin; Stilbenes

Encouraging scientific research into the health effects of dietary bioactive resveratrol has been confounded by its rapid first-pass metabolism, which leads to low in vivo bioavailability. Preliminary studies have shown that resveratrol can modulate gut microbiota composition, undergo biotransformation to active metabolites via the intestinal microbiota, or affect gut barrier function. In rodents, resveratrol can modify the relative Bacteroidetes:Firmicutes ratio and reverse the gut microbial dysbiosis caused by a high-fat diet. By upregulating the expression of genes involved in maintaining tight junctions between intestinal cells, resveratrol contributes to gut barrier integrity. The composition of the gut microbiome and rapid metabolism of resveratrol determines the production of resveratrol metabolites, which are found at greater concentrations in humans after ingestion than their parent molecule and can have similar biological effects. Resveratrol may affect cardiovascular risk factors such as elevated blood cholesterol or trimethylamine

Topics: Animals; Anti-Obesity Agents; Cardiovascular Diseases; Diet, High-Fat; Energy Metabolism; Gastrointestinal Microbiome; Humans; Intestinal Mucosa; Obesity; Resveratrol; Stilbenes

Cardiovascular disease (CVD) retains a leadership as a major cause of human death worldwide. Although a substantial progress was attained in the development of cardioprotective and vasculoprotective drugs, a search for new efficient therapeutic strategies and promising targets is under way. Modulation of epigenetic CVD mechanisms through administration epigenetically active agents is one of such new approaches. Epigenetic mechanisms involve heritable changes in gene expression that are not linked to the alteration of DNA sequence. Pathogenesis of CVDs is associated with global genome-wide changes in DNA methylation and histone modifications. Epigenetically active compounds that influence activity of epigenetic modulators such as DNA methyltransferases (DNMTs), histone acetyltransferases, histone deacetylases (HDACs), etc. may correct these pathogenic changes in the epigenome and therefore be used for CVD therapy. To date, many epigenetically active natural substances (such as polyphenols and flavonoids) and synthetic compounds such as DNMT inhibitors or HDAC inhibitors are known. Both native and chemical DNMT and HDAC inhibitors possess a wide range of cytoprotective activities such as anti-inflammatory, antioxidant, anti-apoptotic, anti-anfibrotic, and anti-hypertrophic properties, which are beneficial of treatment of a variety of CVDs. However, so far, only synthetic DNMT inhibitors enter clinical trials while synthetic HDAC inhibitors are still under evaluation in preclinical studies. In this review, we consider epigenetic mechanisms such as DNA methylation and histone modifications in cardiovascular pathology and the epigenetics-based therapeutic approaches focused on the implementation of DNMT and HDAC inhibitors.

Topics: Animals; Antioxidants; Cardiovascular Diseases; DNA Methylation; Epigenesis, Genetic; Histone Deacetylase Inhibitors; Histones; Humans; Resveratrol; Stilbenes

The relation between alcohol consumption and mortality is a J-shaped curve in most of the many studies published on this topic. The Copenhagen Prospective Population Studies demonstrated in the year 2000 that wine intake may have a beneficial effect on all cause mortality that is additive to that of alcohol. Wine contains various poliphenolic substances which may be beneficial for health and in particular flavonols (such as myricetin and quercetin), catechin and epicatechin, proanthocyanidins, anthocyanins, various phenolic acids and the stilbene resveratrol. In particular, resveratrol seems to play a positive effect on longevity because it increases the expression level of Sirt1, besides its antioxidant, anti-inflammatory and anticarcinogenic properties. Moderate wine drinking is part of the Mediterranean diet, together with abundant and variable plant foods, high consumption of cereals, olive oil as the main (added) fat and a low intake of (red) meat. This healthy diet pattern involves a "Mediterranean way of drinking," that is a regular, moderate wine consumption mainly with food (up to two glasses a day for men and one glass for women). Moderate wine drinking increases longevity, reduces the risk of cardiovascular diseases and does not appreciably influence the overall risk of cancer.

Topics: Alcohol Drinking; Cardiovascular Diseases; Diet, Mediterranean; Female; Flavonols; Humans; Liver Cirrhosis; Longevity; Male; Mediterranean Region; Neoplasms; Phenols; Resveratrol; Risk Factors; Sex Factors; Sirtuins; Stilbenes; Wine

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

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cardiovascular Diseases; Dietary Fats; Humans; Resveratrol; Stilbenes; Wine

Potential effects of resveratrol consumption on cardiovascular disease risk factors and body weight in overweight/obese adults have not been fully elucidated. Our present analysis was to evaluate the effects of resveratrol consumption on risk markers related to cardiovascular health in overweight/obese Individuals.. Multiple literature databases were systematically searched, and 21 studies were included. Effect sizes were expressed as weighted mean difference (WMD) and 95% confidence interval (CI), and heterogeneity was assessed with the I2 test. Publication bias and subgroup analyses were also performed.. There were variations in reporting quality of included studies. Resveratrol intervention significantly lowered total cholesterol (WMD, -0.19 mmol/L; 95% CI, -0.32 to -0.06; P = 0.004), systolic blood pressure (WMD, -2.26 mmHg; 95% CI, -4.82 to -0.49; P = 0.02), and fasting glucose (WMD, -0.22 mmol/L; 95% CI, -0.42 to -0.03; P = 0.03). Heterogeneity was noted for these outcomes (35.6%, 38.7% and 71.4%, respectively). Our subgroup analysis showed significant reductions in total cholesterol, systolic blood pressure, diastolic blood pressure, glucose, and insulin in subjects ingesting higher dose of resveratrol (≥300 mg/day).. Our finding provides evidence that daily resveratrol consumption might be a candidate as an adjunct to pharmacological management to better prevent and control cardiovascular disease in overweight/obese individuals.

Topics: Biomarkers; Blood Pressure; Body Mass Index; Cardiovascular Diseases; Cholesterol; Humans; Insulin Resistance; Meta-Analysis as Topic; Obesity; Overweight; Randomized Controlled Trials as Topic; Reproducibility of Results; Resveratrol; Risk Factors; Stilbenes

Pterostilbene (PS) is a well-recognized antioxidant that primarily exists in blueberries, grapevines and heartwood of red sandalwood. Interest in this compound has been renewed in recent years, and studies have found that PS possesses an array of pharmacological properties, including chemopreventive, antiinflammatory, antidiabetic, antidyslipidemic, antiatherosclerotic and neuroprotective effects. However, the greater in vivo bioavailability of PS, as compared to resveratrol, is an added advantage for its efficacy. This review provides a summary regarding the sources, pharmacokinetic aspects and pharmacodynamics of PS, with a focus on the molecular mechanisms underlying its protective effects against cancer, brain injuries and heart disease. Studies regarding the safety profile of PS have also been included. Based on the presently available evidence, we conclude that PS represents an active phytonutrient and a potential drug with pleiotropic health applications.

Topics: Animals; Cardiovascular Diseases; Central Nervous System Diseases; Humans; Neoplasms; Safety; Stilbenes

Wine is a traditional beverage that has been associated with both healthy and harmful effects. Conceptions like the so-called "French paradox" or the beneficial impact of the Mediterranean diet suggest benefit. Wine has a complex composition, which is affected by whether it is red or white or by other variables, like the variety of grapes or others. Alcohol and phenolic compounds have been attributed a participation in the benefits ascribed to wine. The case of alcohol has been extensively studied, but the key question is whether wine offers additional benefits. Resveratrol, a non-flavonoid compound, and quercetin, a flavonol, have received particular attention. There is much experimental work confirming a beneficial balance for both substances, particularly resveratrol, in various organs and systems. The pharmacological dosages used in many of those experiments have shed doubt, however, on the clinical translation of those findings. Clinical studies are limited by their observational nature as well as for the difficulties to abstract the benefits of wine from other confounders. Notwithstanding the doubts, there is reasonable unanimity in beneficial effects of moderate wine consumption in cardiovascular disease, diabetes, osteoporosis, maybe neurological diseases, and longevity. Observations are less enthusiastic in what refers to cancer. While considering these limitations, clinicians may spread the message that the balance of moderate wine consumption seems beneficial.

Topics: Antioxidants; Cardiovascular Diseases; Humans; Resveratrol; Stilbenes; Vitis; Wine

Cardiovascular disease is the leading cause of death worldwide. Despite advancements in diagnosis and treatment of cardiovascular disease, the incidence of cardiovascular disease is still rising. Therefore, new lines of medications are needed to treat the growing population of patients with cardiovascular disease. Although the majority of the existing pharmacotherapies for cardiovascular disease are synthesized molecules, natural compounds, such as resveratrol, are also being tested. Resveratrol is a non-flavonoid polyphenolic compound, which has several biological effects. Preclinical studies have provided convincing evidence that resveratrol has beneficial effects in animal models of hypertension, atherosclerosis, stroke, ischemic heart disease, arrhythmia, chemotherapy-induced cardiotoxicity, diabetic cardiomyopathy, and heart failure. Although not fully delineated, some of the beneficial cardiovascular effects of resveratrol are mediated through activation of silent information regulator 1 (SIRT1), AMP-activated protein kinase (AMPK), and endogenous anti-oxidant enzymes. In addition to these pathways, the anti-inflammatory, anti-platelet, insulin-sensitizing, and lipid-lowering properties of resveratrol contribute to its beneficial cardiovascular effects. Despite the promise of resveratrol as a treatment for numerous cardiovascular diseases, the clinical studies for resveratrol are still limited. In addition, several conflicting results from trials have been reported, which demonstrates the challenges that face the translation of the exciting preclinical findings to humans. Herein, we will review much of the preclinical and clinical evidence for the role of resveratrol in the treatment of cardiovascular disease and provide information about the physiological and molecular signaling mechanisms involved. This article is part of a Special Issue entitled: Resveratrol: Challenges in translating pre-clinical findings to improved patient outcomes.

Topics: Animals; Blood Pressure; Cardiovascular Agents; Cardiovascular Diseases; Clinical Trials as Topic; Heart Rate; Humans; Resveratrol; Stilbenes; Vasodilation

Lots of epidemiological studies have put forward the beneficial effects of dietary polyphenols consumption in the prevention of diseases related to aging i.e vascular pathologies, neurodegeneration, cancers and associated inflammatory processes. Among polyphenols, resveratrol (trans-3,4',5- trihydroxystilbene, RSV), a naturally occurring stilbene widely distributed in foodstuffs such as grapes and wine, has been the most studied. Researches performed since the last decades in vitro, in animal models and in (pre)clinical studies have pointed out its pleiotropic health benefits by acting on multiple signaling pathways which go beyond its originally described direct antioxidant activity. However, its low bioavailability upon oral ingestion and lack of specificity may hamper the translation of the encouraging experimental data into human health benefits. Herein we provide an overview on the capacity of RSV to regulate oxidative stress-induced signaling and to modulate key components of signal transduction pathways which are commonly altered in cardiovascular, neurodegenerative and cancer pathologies. We also have attempted to provide a comprehensive outlook on RSV metabolism and biological activity of its main metabolites and discussed about the new strategies developed to circumvent its poor bioavailability and to improve its therapeutic efficacy, including synthesis of new derivatives and new formulations for its cell delivery.

Topics: Animals; Antioxidants; Cardiovascular Diseases; Humans; Neoplasms; Neurodegenerative Diseases; Polyphenols; Resveratrol; Signal Transduction; Stilbenes; Wine

The present review discusses the acquisitions obtained to date on the subject of wine consumption, health and cardiovascular protection. We distinguished the cardiovascular effects related to the consumption of wine and other alcoholic beverages focusing on non-alcoholic wine fraction: polyphenols and especially resveratrol. In the second part of the review we have addressed the issue of resveratrol bioavailability and the importance of wine matrix and phytocomplex highlighting the biological effects that can be obtained with nutraceuticals and resveratrol pills compared to the daily consumption of a glass of red wine.

Topics: Alcohol Drinking; Animals; Biological Availability; Cardiovascular Diseases; France; Humans; Polyphenols; Resveratrol; Stilbenes; Wine

Numerous studies have suggested that oral supplementation with resveratrol exerts cardioprotective effects, but evidence of the effects on C-reactive protein (CRP) plasma levels and other cardiovascular (CV) risk factors is inconclusive. Therefore, we performed a meta-analysis to evaluate the efficacy of resveratrol supplementation on plasma CRP concentrations and selected predictors of CV risk.. The search included PUBMED, Cochrane Library, Web of Science, Scopus, and EMBASE (up to August 31, 2014) to identify RCTs investigating the effects of resveratrol supplementation on selected CV risk factors. Quantitative data synthesis was performed using a random-effects model, with weighted mean difference (WMD) and 95% confidence intervals (CI) as summary statistics.. Meta-analysis of data from 10 RCTs (11 treatment arms) did not support a significant effect of resveratrol supplementation in altering plasma CRP concentrations (WMD: -0.144 mg/L, 95% CI: -0.968-0.680, p = 0.731). Resveratrol supplementation was not found to alter plasma levels of total cholesterol (WMD: 1.49 mg/dL, 95% CI: -14.96-17.93, p = 0.859), low density lipoprotein cholesterol (WMD: -0.31 mg/dL, 95% CI: -9.57-8.95, p = 0.948), triglycerides (WMD: 2.67 mg/dL, 95% CI: -28.34-33.67, p = 0.866), and glucose (WMD: 1.28 mg/dL, 95% CI: -5.28-7.84, p = 0.703). It also slightly reduced high density lipoprotein cholesterol concentrations (WMD: -4.18 mg/dL, 95% CI: -6.54 to -1.82, p = 0.001). Likewise, no significant effect was observed on systolic (WMD: 0.82 mmHg, 95% CI: -8.86-10.50, p = 0.868) and diastolic blood pressure (WMD: 1.72 mm Hg, 95% CI: -6.29-9.73, p=0.674).. This meta-analysis of available RCTs does not suggest any benefit of resveratrol supplementation on CV risk factors. Larger, well-designed trials are necessary to confirm these results.

Topics: Antioxidants; C-Reactive Protein; Cardiotonic Agents; Cardiovascular Diseases; Female; Humans; Male; Prognosis; Randomized Controlled Trials as Topic; Resveratrol; Risk Assessment; Severity of Illness Index; Stilbenes; Survival Rate; Treatment Outcome

Cardiovascular diseases remain one of the major health problems worldwide. The worldwide research against cardio-vascular diseases as well as genome wide association studies were successful in indentifying the loci associated with these prominent life threatening diseases but still a substantial amount of casualty remains unexplained. Over the last decade, the thorough understanding of molecular and biochemical mechanisms of cardiac disorders lead to the knowledge of various mechanisms of action of polyphenols to target inflammation during cardiac disorders. The present review article is focused on role of phytochemical resveratrol in regulation of redox signalling, autophagy and inflammation during cardiovascular pathology.

Topics: Animals; Antioxidants; Autophagy; Cardiovascular Diseases; Humans; Oxidation-Reduction; Resveratrol; Stilbenes

The grape antioxidant resveratrol has been a topic of intense research for the past three decades. Resveratrol and other grape ingredients, as well as whole-grape products, have shown considerable promise in health promotion and disease management. Phytochemically, whole grape represents a natural combination of resveratrol and other phytonutrients, as it contains several catechins, anthocyanins, polyphenols, and flavonols. Thus, whole grape products or specific combinations of grape constituents provide us with the possibility of synergistic interactions leading to improved efficacy. Recent research has suggested that whole-grape products may help in maintaining heart health and protect against aging, aging-associated diseases, neurodegeneration, and some cancers. On the basis of available recent literature, the grape fruit or whole-grape products seem to be safer choices for better health and disease prevention. However, for advanced disease conditions, individual grape ingredients (such as resveratrol) or combinations of multiple ingredients, together with existing therapies, appear to be better approaches. Further clinical studies are needed to understand the benefits of grapes and their products in the prevention and management of specific diseases.

Topics: Animals; Cardiovascular Diseases; Clinical Trials as Topic; Diet; Disease Management; Fruit; Humans; Metabolic Diseases; Resveratrol; Stilbenes; Vitis

Resveratrol is a phenolic phytochemical, with a stilbene backbone, derived from edible plants such as grape and peanut. It is a bioactive molecule with physiological effects on multiple organ systems. Its effects range from the neuroprotective to the nephroprotective, including cardiovascular, neuronal, and antineoplastic responses as a part of its broad spectrum of action. In this review, we examine the effects of resveratrol on the following organ systems: the central nervous system, including neurological pathology such as Parkinson's and Alzheimer's disease; the cardiovascular system, including disorders such as atherosclerosis, ischemia-reperfusion injury, and cardiomyocyte hypertrophy; the kidneys, including primary and secondary nephropathies and nephrolithiasis; multiple forms of cancer; and metabolic syndromes including diabetes. We emphasize commonalities in extracellular matrix protein alterations and intracellular signal transduction system induction following resveratrol treatment. We summarize the known anti-inflammatory, antioxidative, and cytoprotective effects of resveratrol across disparate organ systems. Additionally, we analyze the available literature regarding the pharmacokinetics of resveratrol formulations used in these studies. Finally, we critically examine select clinical trials documenting a lack of effect following resveratrol treatment.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Cardiovascular Diseases; Central Nervous System; Humans; Kidney Diseases; Metabolic Diseases; Neuroprotective Agents; Resveratrol; Sirtuin 1; Stilbenes

Resveratrol is a bioactive plant compound that has drawn scientific and media attention owing to its protective effects against a wide variety of illnesses, including cardiovascular diseases and cancer. In the last two decades, a plethora of preclinical studies have shown these beneficial effects, and some of them have been supported by clinical trials. However, there are few epidemiological studies assessing these relationships, showing mostly inconsistent results among them. This could be partially due to the difficulty of accurately estimating dietary resveratrol exposure. The development of Phenol-Explorer, a database containing resveratrol food-composition data, will facilitate the estimation of resveratrol intake. Moreover, the discovery and validation of a nutritional biomarker of this exposure, urinary resveratrol metabolite profile, will allow a more accurate assessment of dietary resveratrol exposure. Few epidemiological studies have assessed the potential health effects of resveratrol. Resveratrol was not associated with total mortality, cancer, or cardiovascular events, but it was associated with an improvement of serum glucose and triglyceride levels and a decrease in heart rate. Together, these findings suggest a potential cardioprotective effect of resveratrol in epidemiological studies, although the evidence is still scarce.

Topics: Animals; Biomarkers; Cardiotonic Agents; Cardiovascular Diseases; Diet; Humans; Nutrition Assessment; Resveratrol; Stilbenes

Cardiovascular diseases represent a worldwide relevant socioeconomical problem. Cardiovascular disease prevention relies also on lifestyle changes, including dietary habits. The cardioprotective effects of several foods and dietary supplements in both animal models and in humans have been explored. It was found that beneficial effects are mainly dependent on antioxidant and anti-inflammatory properties, also involving modulation of mitochondrial function. Resveratrol is one of the most studied phytochemical compounds and it is provided with several benefits in cardiovascular diseases as well as in other pathological conditions (such as cancer). Other relevant compounds are Brassica oleracea, curcumin, and berberine, and they all exert beneficial effects in several diseases. In the attempt to provide a comprehensive reference tool for both researchers and clinicians, we summarized in the present paper the existing literature on both preclinical and clinical cardioprotective effects of each mentioned phytochemical. We structured the discussion of each compound by analyzing, first, its cellular molecular targets of action, subsequently focusing on results from applications in both ex vivo and in vivo models, finally discussing the relevance of the compound in the context of human diseases.

Topics: Animals; Cardiovascular Diseases; Humans; Mice; Phytochemicals; Plant Extracts; Protective Agents; Resveratrol; Stilbenes

The multi-factorial aetiology is the characteristic element of cardiac disorders. Further scientific research had recognized for a long time that platelet function is related to the risk of developing atherosclerosis. Activated blood platelets play a central role in this chronic inflammatory condition as they contribute to plaque formation within blood vessels in the early stages of atherogenesis. The present review article summarizes the cardioprotective role played by Phytochemicals via antiplatelet effects. Also, various metabolic modifications have been included that have protective effect during cardiac pathology.

Topics: Animals; Blood Platelets; Cardiotonic Agents; Cardiovascular Diseases; Flavonoids; Humans; Lignans; Phytochemicals; Platelet Aggregation Inhibitors; Polyphenols; Stilbenes; Tannins

Peanuts are important dietary food source of resveratrol with potent antioxidant properties implicated in reducing risk of cancer, cardiovascular and Alzheimer's disease, and delaying aging. Resveratrol is a naturally occurring stilbene phytoalexin phenolic compound produced in response to a variety of biotic and abiotic stresses. This paper is a review of trans-resveratrol and related stilbenes from peanuts--their chemical structures, mechanisms for their biosynthesis, and concentrations in comparison with other major food sources. It will also discuss trans-resveratrol's absorption, bioavailability, and major health benefits; processes to enhance their biosynthesis in peanuts by biotic and abiotic stresses; process optimization for enhanced levels in peanuts and their potential food applications; and methods used for its extraction and analysis.

Topics: Alzheimer Disease; Antioxidants; Arachis; Biological Availability; Cardiovascular Diseases; Diet; Humans; Neoplasms; Resveratrol; Stilbenes

Adiponectin is produced predominantly by adipocytes and plays an important role in metabolic and cardiovascular homeostasis through its insulin-sensitizing actions and anti-inflammatory and anti-atherogenic properties. Recently, it has been observed that lower levels of adiponectin can substantially increase the risk of developing type 2 diabetes, metabolic syndrome, atherosclerosis, and cardiovascular disease in patients who are obese. Circulating adiponectin levels are inversely related to the inflammatory process, oxidative stress, and metabolic dysregulation. Intensive lifestyle modifications and pharmacologic agents, including peroxisome proliferator-activated receptor-γ or α agonists, some statins, renin-angiotensin-aldosterone system blockers, some calcium channel blockers, mineralocorticoid receptor blockers, new β-blockers, and several natural compounds can increase adiponectin levels and suppress or prevent disease initiation or progression, respectively, in cardiovascular and metabolic disorders. Therefore, it is important for investigators to have a thorough understanding of the interventions that can modulate adiponectin. Such knowledge may lead to new therapeutic approaches for diseases such as type 2 diabetes, metabolic syndrome, cardiovascular disease, and obesity. This review focuses on recent updates regarding therapeutic interventions that might modulate adiponectin.

Topics: Adiponectin; Antihypertensive Agents; Atherosclerosis; Bariatric Surgery; Cardiovascular Diseases; Clinical Trials as Topic; Combined Modality Therapy; Diabetes Mellitus, Type 2; Diet, Reducing; Exercise; Humans; Hypoglycemic Agents; Insulin Resistance; Life Style; Metabolic Syndrome; Metabolism, Inborn Errors; Obesity; Peroxisome Proliferator-Activated Receptors; Receptors, Adiponectin; Resveratrol; Stilbenes

The incidence of cardiovascular diseases (CVDs) is high in both developed and developing countries. It has a high global rate of mortality and causes heavy social burden. Drugs are available for managing or treating CVDs and its complications. Consumption of dietary supplements or functional foods for reducing the risk of CVDs has also gained wide recognition by the general public. Piceatannol, an analog and metabolite of resveratrol, is a natural stilbene commonly found in the skin of grapes and wine. Piceatannol is believed to be a potent compound with certain cardiovascular therapeutic effects, such as the prevention of hypercholesterolemia, arrhythmia, atherosclerosis, and angiogenesis. It also has vasorelaxation and antioxidant activities. A comprehensive review of piceatannol concludes that piceatannol has the potential to be developed into health products for the cardiovascular system to help modern society reduce the high CVD incidence. However, further investigations are warranted in order to increase the bioavailability and understand the biological mechanisms and safety of using piceatannol.

Topics: Animals; Cardiovascular Diseases; Humans; Stilbenes

Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a natural polyphenolic compound that exists in Polygonum cuspidatum, grapes, peanuts and berries, as well as their manufactured products, especially red wine. Resveratrol is a pharmacologically active compound that interacts with multiple targets in a variety of cardiovascular disease models to exert protective effects or induce a reduction in cardiovascular risks parameters. This review attempts to primarily serve to summarize the current research findings regarding the putative cardioprotective effects of resveratrol and the molecular pathways underlying these effects. One intent is to hopefully provide a relatively comprehensive resource for clues that may prompt ideas for additional mechanistic studies which might further elucidate and strengthen the role of the stilbene family of compounds in cardiovascular disease and cardioprotection. Model systems that incorporate a significant functional association with tissues outside of the cardiovascular system proper, such as adipose (cell culture, obesity models) and pancreatic (diabetes) tissues, were reviewed, and the molecular pathways and/or targets related to these models and influenced by resveratrol are discussed. Because the body of work encompassing the stilbenes and other phytochemicals in the context of longevity and the ability to presumably mitigate a plethora of afflictions is replete with conflicting information and controversy, especially so with respect to the human response, we tried to remain as neutral as possible in compiling and presenting the more current data with minimal commentary, permitting the reader free reign to extract the knowledge most helpful to their own investigations.

Topics: Animals; Cardiotonic Agents; Cardiovascular Diseases; Humans; Resveratrol; Stilbenes

The prevention of cardiovascular and osteoporotic risk is a topic of great importance in the peri- and postmenopausal periods. This paper reviews the role of resveratrol, inositol, vitamin D and K in the prevention of cardiovascular and osteoporotic risk in peri- and post-. The phytoestrogen-like activity of resveratrol has potential clinical implications in the gynecological practice. In particular transresveratrol inhibits low-density lipoprotein oxidation, which is a recognized risk factor for cardiovascular diseases. Resveratrol has also a documented antiplatelet effect and may prevent cardiovascular diseases inhibiting the cardiac fibroblasts proliferation. With regard to bone health, in in vitro studies resveratrol has shown activities in osteoblastic MC3T3-E1 cells. Resveratrol also interacts with vitamin D in promoting bone health. Resveratrol is considered a caloric restriction mimetic and potentially effects factors involved in the metabolic syndrome. Myo-inositol has documented in clinical studies its effectiveness in improving the metabolic syndrome in post menopausal women. Thus the supplementation with inositol and resveratrol may be useful in the prevention of insulin resistance and consequently metabolic syndrome and cardiovascular diseases risk. Finally vitamin K2 effects calcium metabolisms and subjects with higher levels of calcium in the bones tend to have a lower frequency of vascular calcifications and a lower cardiovascular risk. Vitamin K2 also has a key role in the bone homeostasis. A supplement including resveratrol, inositol, vitamin K and vitamin D offers a novel opportunity to the woman in peri- and postmenopause.

Topics: Animals; Cardiovascular Diseases; Cell Line; Female; Humans; Inositol; Mice; Osteoporosis, Postmenopausal; Perimenopause; Postmenopause; Resveratrol; Risk Factors; Stilbenes; Vitamin D; Vitamin K

Intake of dietary phytochemicals has frequently been associated with health benefits. Noninfectious diseases including cardiovascular disease (CVD), cancer and diabetes are major causes of death, whereas dementia cases are also increasing to 'epidemic' proportion. This review will focus on recent progress on mechanisms underlying the potential role of dietary phytochemicals in CVD, diabetes, cancer and dementia, with consideration of the latest clinical data.. The association of tea (Camellia sinensis), particularly catechins, with reported mechanistic effects for CVD, diabetes, cancer and cognition contributes to our understanding of the suggested benefits of tea consumption on health from limited and inconclusive clinical trial and epidemiological data. Resveratrol, which occurs in grapes (Vitis vinifera) and wine, and curcumin, a component of turmeric (Curcuma longa), are also emerging as potentially relevant to health, particularly for CVD and dementia, with some promising data also concluded for curcumin in cancer. Other phytochemicals mechanistically relevant for health include anthocyanins, isoflavones and glucosinolates, which are also discussed.. Evidence for the role of phytochemicals in health and disease is growing, but associations between phytochemicals and disease need to be more firmly understood and established from more robust clinical data using preparations that have been phytochemically characterized.

Topics: Cardiovascular Diseases; Catechin; Clinical Trials as Topic; Curcuma; Curcumin; Dementia; Diabetes Mellitus; Humans; Micronutrients; Neoplasms; Phytochemicals; Plant Extracts; Resveratrol; Stilbenes; Tea; Vitis; Wine

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.

Topics: Animals; Cardiovascular Diseases; Endothelial Cells; Endothelium, Vascular; Humans; Nitric Oxide; Nitric Oxide Synthase Type III; Protein Binding; Resveratrol; Stilbenes

Resveratrol, a natural compound endowed with multiple health-promoting effects, has received much attention given its potential for the treatment of cardiovascular, inflammatory, neurodegenerative, metabolic and age-related diseases. However, the translational potential of resveratrol has been limited by its specificity, poor bioavailability and uncertain toxicity. In recent years, there has been an accumulation of evidence demonstrating that resveratrol modulates sphingolipid metabolism. Moreover, resveratrol forms higher order oligomers that exhibit better selectivity and potency in modulating sphingolipid metabolism. This review evaluates the evidence supporting the modulation of sphingolipid metabolism and signaling as a mechanism of action underlying the therapeutic efficacy of resveratrol and oligomers in diseases, such as cancer.

Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Binding Sites; Cardiovascular Diseases; Drug Discovery; Humans; Molecular Docking Simulation; Molecular Structure; Neoplasms; Neurodegenerative Diseases; Resveratrol; Signal Transduction; Sphingolipids; Stilbenes

Polyphenols are compounds found in foods such as tea, coffee, cocoa, olive oil, and red wine and have been studied to determine if their intake may modify cardiovascular disease (CVD) risk. Historically, biologic actions of polyphenols have been attributed to antioxidant activities, but recent evidence suggests that immunomodulatory and vasodilatory properties of polyphenols may also contribute to CVD risk reduction. These properties will be discussed, and recent epidemiological evidence and intervention trials will be reviewed. Further identification of polyphenols in foods and accurate assessment of exposures through measurement of biomarkers (i.e., polyphenol metabolites) could provide the needed impetus to examine the impact of polyphenol-rich foods on CVD intermediate outcomes (especially those signifying chronic inflammation) and hard endpoints among high risk patients. Although we have mechanistic insight into how polyphenols may function in CVD risk reduction, further research is needed before definitive recommendations for consumption can be made.

Topics: Antioxidants; Cardiovascular Diseases; Flavonoids; Food; Humans; Immunomodulation; Lignans; Phenols; Polyphenols; Risk Factors; Stilbenes; Vasodilation

Besides synthesizing nutritive substances (proteins, fats and carbohydrates) for energy and growth, plants produce numerous non-energetic so-called secondary metabolites (mainly polyphenols) that allow them to protect themselves against infections and other types of hostile environments. Interestingly, these polyphenols often provide cells with valuable bioactive properties for the maintenance of their functions and homeostasis (signaling, gene regulation, protection against acquired or infectious diseases, etc.) both in humans and animals. Namely, from a nutritional point of view, and based on epidemiological data, it is now well accepted that the regular consumption of green vegetables, fruits and fibers has protective effects against the onset of cancer as well as of inflammatory, neurodegenerative, metabolic and cardiovascular diseases, and consequently increases the overall longevity. In particular, grapevine plants produce large amounts of a wide variety of polyphenols. The most prominent of those-resveratrol-has been shown to impair or delay cardiovascular alterations, cancer, inflammation, aging, etc. Until recently, the molecular bases of the pleiotropic effects of resveratrol remained largely unclear despite numerous studies on a variety of signaling pathways and the transcriptional networks that they control. However, it has been recently proposed that the protective properties of resveratrol may arise from its modulation of small non-coding regulatory RNAs, namely microRNAs. The aim of this review is to present up-to-date data on the control of microRNA expression by dietary phytophenols in different types of human cells, and their impact on cell differentiation, cancer development and the regulation of the inflammatory response.

Topics: Animals; Antioxidants; Cardiovascular Diseases; Cell Differentiation; Cell Physiological Phenomena; Diet; Dietary Fiber; Fruit; Gene Expression; Homeostasis; Humans; Inflammation; MicroRNAs; Neoplasms; Phenols; Plants; Polyphenols; Resveratrol; Signal Transduction; Stilbenes; Vegetables

Numerous scientific papers have suggested health-promoting effects of resveratrol, including claims in the prevention of diseases such as coronary heart disease, diabetes, and cancer. Therefore, it was proposed that the scientific community needed to express recommendations on the human use of resveratrol. Such recommendations were formulated after the first international resveratrol conference in Denmark, Resveratrol2010. The working group stated that the evidence was "not sufficiently strong to justify recommendation for the chronic administration of resveratrol to human beings, beyond the dose which can be obtained from dietary sources." It was a disappointing conclusion relative to the positive claims about the therapeutic potential of resveratrol made by the media. However, since 2010, results from the first clinical trials on resveratrol have been made available. Because of these emerging results, it is necessary to formulate updated versions of the recommendations.

Topics: Animals; Cardiovascular Diseases; Clinical Trials as Topic; Humans; Neoplasms; Practice Guidelines as Topic; Resveratrol; Stilbenes

Primary prevention of cardiovascular disease (CVD) aims to avoid a first event in subjects that are at risk but have not yet been diagnosed with heart disease. Secondary prevention of CVD aims to avoid new events in patients with established heart disease. Both approaches involve clinical intervention and implementation of healthy lifestyles. The grape and wine polyphenol resveratrol (3,5,4'-trihydroxy-trans-stilbene) has shown cardioprotective benefits in humans. Most of these approaches deal with rather high doses and short follow-ups, and do not address the issue of long-term resveratrol consumption safety, especially in medicated individuals. Here, we review the trials conducted with resveratrol in patients at risk for or with established CVD, focusing on the two longest human clinical trials reported so far (1-year follow-up). We also discuss the expectations for resveratrol from a dietary and clinical perspective in relation to CVD. However, statistically significant changes in CVD-risk markers do not necessarily equal clinical significance in the daily care of patients.

Topics: Animals; Cardiotonic Agents; Cardiovascular Diseases; Clinical Trials as Topic; Humans; Primary Prevention; Resveratrol; Secondary Prevention; Stilbenes; Vitis; Wine

Impairments of endothelial function, which can be assessed noninvasively by flow-mediated dilation (FMD) of the brachial artery, contribute to the development of cardiovascular disease. Associations between FMD and cognition suggest a vascular component in the loss of cognitive function. Certain vasoactive nutrients that have been shown to improve FMD may also have the potential to enhance cerebral perfusion and cognition. Preclinical studies show that trans-resveratrol can enhance nitric oxide bioavailability, thereby increasing endothelium-dependent vasodilation. We have now shown that acute administration of resveratrol elicits dose-dependent increases of FMD with greater potency than other vasoactive nutrients and that this benefit is sustained following regular consumption. We describe the potential implications of this vasodilator benefit of resveratrol and its role in enhancing cerebrovascular and cognitive functions.

Topics: Animals; Cardiovascular Diseases; Humans; Resveratrol; Stilbenes; Vasodilator Agents

Through its antioxidant, anticarcinogenic, and anti-inflammatory properties, resveratrol has become a candidate for drug development in the context of aging studies. Scientific evidence has highlighted its potential as a therapeutic agent for cardiovascular diseases and some cancers but also as an antiaging molecule. Resveratrol is thought to mimic the beneficial effects of chronic and moderate calorie restriction. Nevertheless, no study has demonstrated the prolongation of life span in healthy nonobese mammal models. This review summarizes recent findings on the effects of resveratrol on aging and life span in mammals. In our opinion, more studies should be performed to assess the effects of a chronic dietary intake of resveratrol in long-lived species close to humans, such as nonhuman primates. This will certainly generate more evidence about the ability of resveratrol to achieve the physiological benefits that have been observed in small mammal laboratory models and feature the eventual unwanted secondary effects that may occur under high levels of resveratrol.

Topics: Aging; Animals; Antioxidants; Biomarkers; Cardiovascular Diseases; Humans; Longevity; Mammals; Resveratrol; Stilbenes

Resveratrol is a naturally occurring polyphenol found in the skin of red grapes, peanuts, and red wine that has been shown to modify many cardiovascular risk factors. Small animal models have been extensively used to investigate cardiovascular disease, but the results often fail to translate in clinical trials. Disease-specific pig models are emerging as clinically useful tools that may offer insight into cardiovascular disease and the effect of drugs such as resveratrol on cardiovascular health. In this paper, we discuss the advantage of using clinically relevant pig models of diabetes, hypercholesterolemia, and myocardial ischemia to investigate the role of resveratrol in cardiovascular disease prevention.

Topics: Animals; Cardiotonic Agents; Cardiovascular Diseases; Disease Models, Animal; Humans; Resveratrol; Species Specificity; Stilbenes; Swine; Treatment Outcome

The polyphenol resveratrol is found notably in grapes and in a variety of medicinal plants. Recently, resveratrol has been suggested to have cardioprotective effects and to improve metabolic health by mimicking the effects of calorie restriction. Numerous animal and in vitro studies suggest that resveratrol could improve cardiovascular and metabolic health in humans. In view of this compelling preclinical evidence, several human studies investigating the effects of resveratrol on vascular and metabolic health have been initiated. Collectively, the animal, human epidemiological, and first human intervention studies support a role of resveratrol in vascular and metabolic health. This has led to the introduction of the first supplement and food products containing resveratrol and its emergence as a promising new health ingredient. Thus, supplementation with resveratrol may be included in nutritional and lifestyle programs aiming to reduce the risk of vascular and obesity-related problems.

Topics: Animals; Biomedical Research; Caloric Restriction; Cardiovascular Diseases; Dietary Supplements; Food; Humans; Nutritional Status; Resveratrol; Statistics as Topic; Stilbenes

Resveratrol-a natural polyphenolic compound-was first discovered in the 1940s. Although initially used for cancer therapy, it has shown beneficial effects against most cardiovascular and cerebrovascular diseases. A large part of these effects are related to its antioxidant properties. Here we review: (a) the sources, the metabolism, and the bioavailability of resveratrol; (b) the ability of resveratrol to modulate redox signalling and to interact with multiple molecular targets of diverse intracellular pathways; (c) its protective effects against oxidative damage in cardio-cerebro-vascular districts and metabolic disorders such as diabetes; and (d) the evidence for its efficacy and toxicity in humans. The overall aim of this review is to discuss the frontiers in the field of resveratrol's mechanisms, bioactivity, biology, and health-related use.

Topics: Antioxidants; Biological Availability; Cardiovascular Diseases; Cerebrovascular Disorders; Clinical Trials as Topic; Diabetes Mellitus; Humans; Metabolic Diseases; Oxidation-Reduction; Oxidative Stress; Resveratrol; Stilbenes

The phytochemicals present in fruits and vegetables may play an important role in deceasing chronic disease risk. Grapes, one of the most popular and widely cultivated and consumed fruits in the world, are rich in phytochemicals. Epidemiological evidence has linked the consumption of grapes with reduced risk of chronic diseases, including certain types of cancer and cardiovascular disease. In vitro and in vivo studies have shown that grapes have strong antioxidant activity, inhibiting cancer cell proliferation and suppressing platelet aggregation, while also lowering cholesterol. Grapes contain a variety of phytochemicals, like phenolic acids, stilbenes, anthocyanins, and proanthocyanidins, all of which are strong antioxidants. The phytochemical composition of grapes, however, varies greatly among different varieties. While extensive research exists, a literature review of the health benefits of grapes and their phytochemicals has not been compiled to summarize this work. The aim of this paper is to critically review the most recent literature regarding the concentrations, biological activities, and mechanisms of grape phytochemicals.

Topics: Antioxidants; Cardiovascular Diseases; Flavonoids; Fruit; Health Promotion; Humans; Hydroxybenzoates; Neoplasms; Phenols; Phytochemicals; Plant Extracts; Platelet Aggregation Inhibitors; Stilbenes; Vitis; Wine

Resveratrol, a natural polyphenol, has gained attention in recent years because of its connection with the health benefits of red wine and its anticancer activity in vitro. Studies in animal models have demonstrated beneficial effects on glucose metabolism, vascular function and anti-inflammatory and antioxidant properties. Human studies designed to understand the role of resveratrol in the prevention and treatment of age-related conditions such as diabetes, heart disease, and cancer have recently been undertaken.. We searched PubMed for original articles that reported studies of resveratrol in humans, using search terms, including resveratrol, human studies, glucose metabolism, vascular function, and inflammation. We also searched the reference lists of identified articles for additional papers and sought expert opinion on relevant studies.. Resveratrol treatment has shown beneficial effects on glucose and lipid metabolism in some, but not all studies. Study population, resveratrol source, and dose have varied widely, potentially explaining inconsistent findings. Improvements were noted in endothelial function, systolic blood pressure, and markers of oxidative stress and inflammation in several studies.. Despite the strong preclinical evidence of positive cardiometabolic effects, studies to date have not confirmed resveratrol's benefit in humans. Study variability and methodological issues limit interpretation of available results. Additional research, focusing on subjects with defined metabolic defects and using a range of doses, is needed to advance the field.

Topics: Animals; Antioxidants; Cardiovascular Diseases; Glucose Metabolism Disorders; Humans; Inflammation; Oxidative Stress; Resveratrol; Stilbenes

A systematic review and meta-analysis of available evidence was conducted to obtain a conclusive result on the lipid-modulating effects of resveratrol. Seven randomized controlled trials with a total of 282 subjects (141 in each group) met the eligibility criteria. Overall, resveratrol supplementation had no significant effect on any of the lipid parameters assessed: total cholesterol (weighted mean difference [WMD] -8.70; 95% confidence interval [95% CI] -21.54-4.14; P = 0.18), low-density lipoprotein cholesterol (WMD -3.22; 95% CI -12.56-6.12); P = 0.50), high-density lipoprotein cholesterol (WMD -0.26; 95% CI -4.25-3.73; P = 0.90), and triglycerides (WMD -4.30; 95% CI -20.22-11.63; P = 0.60). These results were robust in sensitivity analysis and were not dependent on the resveratrol dose, the duration of supplementation, or the cardiovascular risk status of the population studied. While future large-scale, well-designed trials are warranted, the current evidence suggests that mechanisms other than hypolipidemic effects account for the established cardioprotective properties of resveratrol.

Topics: Cardiovascular Diseases; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Humans; Lipid Metabolism; Lipids; Randomized Controlled Trials as Topic; Resveratrol; Risk Factors; Stilbenes; Triglycerides

Resveratrol, a star natural product from red wine, has attracted increasing attention around the world. In recent years, resveratrol derivatives (including its oligomers) have shown amazing chemical diversity and biological activities. They have been emerging to be promising new sources of natural antioxidant. This review summarizes recent finding on antioxidant activities of resveratrol derivatives and the structure-activity relationship for the first time. Scientific evidences have highlighted their potential as therapeutic agents for cerebral and cardiovascular diseases. In our opinion, more effort should be devoted to the synthesis of resveratrol oligomers. Based on the structure-activity relationship, screening for resveratrol derivatives with higher antioxidant activity than trans-resveratrol is warranted, and these molecules may have greater therapeutic potential in future investigations.

Topics: Antioxidants; Brain Diseases; Cardiovascular Diseases; Humans; Resveratrol; Stilbenes

Resveratrol is a well-known antioxidant that exists in grape skin/seed, red wine, and the root of Polygonum cuspidatum, a traditional Chinese and Japanese medicinal material. Studies have found that resveratrol has many interesting properties, including anti-carcinogenic properties, anti-microbial and antiviral effects, the ability to reverse dyslipidemia and obesity, the ability to attenuate hyperglycemia and hyperinsulinemia, and the ability to protect endothelial function. Heart failure is the final consequence of the majority of cardiovascular diseases, and resveratrol has been shown to directly attenuate heart contraction. The cardiovascular protective capacities of resveratrol are associated with multiple molecular targets and may lead to the development of novel therapeutic strategies for atherosclerosis, ischemia/reperfusion, metabolic syndrome, and heart failure. This article will mainly review recently published basic researches about the protective cardiovascular effects of resveratrol because these results may lead to the development of new clinical therapeutics in patients.

Topics: Acetyl-CoA Carboxylase; AMP-Activated Protein Kinases; Antioxidants; Cardiovascular Diseases; Heart Failure; Humans; Resveratrol; Sirtuin 1; Stilbenes

A reduction in calorie intake [caloric restriction (CR)] appears to consistently decrease the biological rate of aging in a variety of organisms as well as protect against age-associated diseases including chronic inflammatory disorders such as cardiovascular disease and diabetes. Although the mechanisms behind this observation are not fully understood, identification of the main metabolic pathways affected by CR has generated interest in finding molecular targets that could be modulated by CR mimetics. This review describes the general concepts of CR and CR mimetics as well as discusses evidence related to their effects on inflammation and chronic inflammatory disorders. Additionally, emerging evidence related to the effects of CR on periodontal disease in non-human primates is presented. While the implementation of this type of dietary intervention appears to be challenging in our modern society where obesity is a major public health problem, CR mimetics could offer a promising alternative to control and perhaps prevent several chronic inflammatory disorders including periodontal disease.

Topics: Adaptive Immunity; Animals; Biomimetics; Caloric Restriction; Cardiovascular Diseases; Chronic Disease; Diabetes Mellitus; Humans; Immunity, Innate; Inflammation; Inflammation Mediators; Insulin-Like Growth Factor I; Metformin; Periodontitis; Resveratrol; Signal Transduction; Sirolimus; Sirtuins; Stilbenes; TOR Serine-Threonine Kinases

Resveratrol, a natural polyphenol abundantly found in grape skins and red wine, possesses diverse biochemical and physiological actions, including anti-inflammatory, anti-oxidation, anti-proliferation and promotion of differentiation, and chemopreventive effects. Recently, it is attracting increased attention due to its health benefits, especially in common age-related diseases such as cardiovascular disease, cancer, type 2 diabetes, and neurological conditions. In this review, we discuss the latest cellular and molecular findings that account for the beneficial actions of resveratrol.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Antioxidants; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Neurodegenerative Diseases; Platelet Aggregation Inhibitors; Resveratrol; Stilbenes

Aging is a well-recognized risk factor in the development of cardiovascular disease, which is the primary cause of death and disability in the elderly population. The normal process of aging is associated with progressive deterioration in structure and function of the heart and vasculature. These age-related changes likely act as both a catalyst and accelerator in the development of cardiovascular disease. Since the aging population is one of the fastest growing segments of the population, it is of vital importance that we have a thorough understanding of the physiological changes that occur with aging that contribute to the high incidence of cardiovascular disease in this population. This insight will allow for the development of more targeted therapies that can prevent and treat these conditions. One such anti-aging strategy that has received considerable attention as of late is calorie restriction. Calorie restriction has emerged as one of the most effective and reproducible interventions for extending lifespan, as well as protecting against obesity, metabolic disorders, and cardiovascular disease. Herein, we review the multiple beneficial effects that calorie restriction and resveratrol exert on the cardiovascular system with a particular focus on aging. Although calorie restriction and resveratrol have proven to be very effective in preventing and treating the development of cardiovascular disease in animal models, studies continue as to whether these profound beneficial effects can translate to humans to improve cardiovascular health.

Topics: Aged; Aging; Antimutagenic Agents; Caloric Restriction; Cardiovascular Diseases; Humans; Longevity; Resveratrol; Risk Factors; Stilbenes

Oxidative stress plays an important part in the appearance and development of cardiovascular diseases. In this context, overproduction of reactive oxygen species leads to deregulation of metabolic pathways, such as cell proliferation or inflammation, which interferes with the homeostasis of vascular endothelium. Oxidative stress can decrease the bioavailability of nitric oxide (*NO) in vessels. This decrease is highly associated with endothelial dysfunction. The "French paradox" is a phenomenon that associates a diet rich in saturated fatty acids and a moderate consumption of wine to a low prevalence of cardiovascular diseases. During the past 10 years, the beneficial effects of wine on cardiovascular diseases have been attributed to the actions of resveratrol and other polyphenols. One of the mechanisms involved in these beneficial effects is the capacity of resveratrol and some other stilbene derivatives to maintain sufficient *NO bioavailability in vascular endothelium. This review presents the latest findings on the molecular effects of resveratrol and other stilbene derivatives on the various actors that modulate *NO bioavailability during oxidative stress.

Topics: Animals; Antioxidants; Arginine; Biological Availability; Cardiovascular Diseases; Diet, Atherogenic; Endothelium, Vascular; Fatty Acids; Humans; Mice; Nitric Oxide; Oxidative Stress; Polyphenols; Rabbits; Rats; Reactive Oxygen Species; Resveratrol; Stilbenes; Wine

Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a polyphenol phytoalexin present in a variety of plant species and has been implicated to explain the health benefits of red wine. A wide range of health beneficial effects have been demonstrated for resveratrol in animal studies. In this review, we summarize the cardiovascular effects of resveratrol with emphasis on the molecular targets of the compound. In this regard, resveratrol stimulates endothelial production of nitric oxide, reduces oxidative stress, inhibits vascular inflammation and prevents platelet aggregation. In animal models of cardiovascular disease, resveratrol protects the heart from ischemia-reperfusion injury, reduces blood pressure and cardiac hypertrophy in hypertensive animals, and slows the progression of atherosclerosis. A number of direct and indirect target molecules mediating the aforementioned cardiovascular effects of resveratrol have been identified. These include, among others, the estrogen receptor α, the adenosine receptors, the cyclooxygenase 1, the histone/protein deacetylase sirtuin 1, the AMP-activated protein kinase, the Akt kinase, the nuclear factor-E2-related factor-2, and NF-κB. Molecular mechanisms involved in the signal cascades are discussed.

Topics: Animals; Cardiovascular Agents; Cardiovascular Diseases; Humans; Molecular Targeted Therapy; Nitric Oxide; Resveratrol; Stilbenes

Resveratrol (3,5,4'-trihydroxystilbene) is a natural phytophenol. It is found in many plants, but the highest concentration was detected in different grape-derived products, especially in red wine. The substance is also an active ingredient of some over-the-counter diet supplements. High resveratrol popularity is a consequence of wide biological properties. Numbers of epidemiological and experimental studies have proved a complex chemiopreventive activity of resveratrol against various cardio-vascular disorders and cancer. Furthermore, the compound possesses anti-inflammatory activity and positively regulates glucose level and metabolism of adipose tissue. Diet rich in resveratrol promotes longevity and attenuates neurodegenerative diseases.

Topics: Adipose Tissue; Animals; Anti-Inflammatory Agents; Atherosclerosis; Cardiovascular Diseases; Chemoprevention; Glucose; Humans; Longevity; Neoplasms; Neurodegenerative Diseases; Resveratrol; Stilbenes

Resveratrol (3,5,4'-trans-trihydroxystilbene) is a naturally occurring phytoalexin that is found in medicinal plants, grape skin, peanuts and red wine. Resveratrol exhibits a remarkable range of biological activities, including anticancer activity, antitubulin activity, anti-cardiovascular disease activity, etc. Several other natural products are structurally similar to resveratrol and also present in food. In addition, a series of resveratrol derivatives have been synthesized by the addition of defined functional groups to increase the potency or enhance the activity of specific properties of resveratrol. These resveratrol derivatives might provide promising functions as cardiovascular disease chemopreventive agents. In this review, we will attempt to summarize the main developments of resveratrol derivatives in cardiovascular disease and the main developments have occurred in derivatives of resveratrol's structure-activity relationship and cardiovascular disease over the last couple of decades.

Topics: AMP-Activated Protein Kinases; Apoptosis; Cardiovascular Agents; Cardiovascular Diseases; Humans; Hydroxamic Acids; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Resveratrol; Sirtuin 1; Stilbenes

Resveratrol is a polyphenolic flavonoid found in a diversity of plants, especially berry fruits and is a popular nutritional supplement. It is known to have antioxidant, anti-inflammatory, and anticarcinogenic properties. Recently, additional evidence has been found that resveratrol is beneficial to metabolic and cardiovascular health and may increase the life expectancy of various organisms. These biological effects are widely believed to be due to the ability of resveratrol to activate silent mating-type information regulation 2 homolog 1, a nicotinamide adenine dinucleotide-dependent deacetylase. However, other research has shown that 5'-adenosine monophosphate-activated kinase and not silent mating-type information regulation 2 homolog 1 may be the target of resveratrol. A recent study reported that resveratrol directly inhibits cyclic adenosine monophosphate-specific phosphodiesterases and then activates 5'-adenosine monophosphate-activated kinase. Therefore, the mechanism underlying the diverse nutritional and therapeutic activities of resveratrol needs to be further explored. Furthermore, the optimal dose and possible adverse effects of resveratrol in humans are completely clear. The purpose of this review is to present some of the newly discovered biological effects of resveratrol, including autophagy and stem cell regulation, and research opportunities for the application of resveratrol in cardiovascular and metabolic health. Described herein is the recent understanding of the mechanism of action of resveratrol and future research directions to ascertain the potential of this flavonoid that is present in food.

Topics: AMP-Activated Protein Kinases; Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Autophagy; Cardiovascular Diseases; Disease Models, Animal; Humans; Metabolic Diseases; Resveratrol; Signal Transduction; Sirtuin 1; Stilbenes

Resveratrol, initially used for cancer therapy, has shown beneficial effects against most degenerative and cardiovascular diseases from atherosclerosis, hypertension, ischemia/reperfusion, and heart failure to diabetes, obesity, and aging. The cardioprotective effects of resveratrol are associated with its preconditioning-like action potentiated by its adaptive response. During preconditioning, small doses of resveratrol can exert an adaptive stress response, forcing the expression of cardioprotective genes and proteins such as heat shock and antioxidant proteins. Similarly, resveratrol can induce autophagy, another form of stress adaptation for degrading damaged or long-lived proteins, as a first line of protection against oxidative stress. Resveratrol's interaction with multiple molecular targets of diverse intracellular pathways (e.g., action on sirtuins and FoxOs through multiple transcription factors and protein targets) intertwines with those of the autophagic pathway to give support in the modified redox environment after stem cell therapy, which leads to prolonged survival of cells. The successful application of resveratrol in therapy is based upon its hormetic action similar to any toxin: exerting beneficial effects at lower doses and cytotoxic effects at higher doses.

Topics: Animals; Cardiotonic Agents; Cardiovascular Diseases; Cardiovascular System; Cell Survival; Health Status; Humans; Longevity; Resveratrol; Stilbenes

Cardiovascular diseases are the most common cause of death among the elderly in the Western world. Resveratrol (3,5,4'-trihydroxystilbene) is a plant-derived polyphenol that was shown to exert diverse anti-aging activity mimicking some of the molecular and functional effects of caloric restriction. This mini-review focuses on the molecular and cellular mechanisms activated by resveratrol in the vascular system, and explores the links between its anti-oxidative and anti-inflammatory effects, which could be exploited for the prevention or amelioration of vascular aging in the elderly.

Topics: Aging; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cardiovascular Diseases; Humans; Oxidative Stress; Resveratrol; Stilbenes

In the past decade, the small polyphenol resveratrol has received widespread attention as either a potential therapy or as a preventive agent for numerous diseases. Studies using purified enzymes, cultured cells, and laboratory animals have suggested that resveratrol has anti-aging, anti-carcinogenic, anti-inflammatory, and anti-oxidant properties that might be relevant to chronic diseases and/or longevity in humans. Although the supporting research in laboratory models is quite substantial, only recently data has emerged to describe the effects of resveratrol supplementation on physiological responses in humans. The limited number of human clinical trials that are available has largely described various aspects of resveratrol's safety and bioavailability, reaching a consensus that it is generally well-tolerated, but have poor bioavailability. Very few published human studies have explored the ability of resveratrol to achieve the physiological benefits that have been observed in laboratory models, although many clinical trials have recently been initiated. This review aims to examine the current state of knowledge on the effects of resveratrol on humans and to utilize this information to develop further guidelines for the implementation of human clinical trials.

Topics: Animals; Biological Availability; Cardiovascular Diseases; Clinical Trials as Topic; Diabetes Mellitus; Dietary Supplements; Humans; Liver; Obesity; Oxidative Stress; Resveratrol; Stilbenes; Wine

Calorie restriction is one of the most effective nutritional interventions that reproducibly protects against obesity, diabetes and cardiovascular disease. Recent evidence suggests that even when implemented over a short period, calorie restriction is a safe and effective treatment for cardiovascular disease. Herein, we review the effects of calorie restriction on the cardiovascular system as well as the biological effects of resveratrol, the most widely studied molecule that appears to mimic calorie restriction. An overview of microarray data reveals that the myocardial transcriptional effects of calorie restriction overlap with the transcriptional responses to resveratrol treatment. In addition, calorie restriction and resveratrol modulate similar pathways to improve mitochondrial function, reduce oxidative stress and increase nitric oxide production that are involved in atherosclerosis prevention, blood pressure reduction, attenuation of left-ventricular hypertrophy, resistance to myocardial ischemic injury and heart failure prevention. We also review the data that suggest that the effects of calorie restriction and resveratrol on the cardiovascular system may involve signaling through the silent information regulator of transcription (SIRT), Akt and the AMP-activated protein kinase (AMPK) pathways. While accumulating data demonstrate the health benefits of calorie restriction and resveratrol in experimental animal models, whether these interventions translate to patients with cardiovascular disease remains to be determined.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Caloric Restriction; Cardiovascular Diseases; Humans; Resveratrol; Stilbenes; Vasodilator Agents

Although heavy alcohol consumption has deleterious effects on heart health, moderate drinking is thought to have cardioprotective effects, reducing the risk of coronary artery disease and improving prognosis after a myocardial infarction. It still is unclear, however, if this effect can be achieved with all types of alcoholic beverages and results from the alcohol itself, from other compounds found in alcoholic beverages, or both. For example, the polyphenolic compound resveratrol, which is found particularly in red wine, can reduce the risk of atherosclerosis; however, it is not clear if the resveratrol levels present in wine are sufficient to achieve this result. Alcohol itself contributes to cardioprotection through several mechanisms. For example, it can improve the cholesterol profile, increasing the levels of "good" cholesterol and reducing the levels of "bad" cholesterol. Alcohol also may contribute to blood clot dissolution and may induce a phenomenon called pre-conditioning, whereby exposure to moderate alcohol levels (like short bouts of blood supply disruption [i.e., ischemia]), and result in reduced damage to the heart tissue after subsequent prolonged ischemia. Finally, the enzyme aldehyde dehydrogenase (ALDH) 2, which is involved in alcohol metabolism, also may contribute to alcohol-related cardioprotection by metabolizing other harmful aldehydes that could damage the heart muscle.

Topics: Alcohol Drinking; Alcoholic Beverages; Aldehyde Dehydrogenase; Aldehyde Dehydrogenase, Mitochondrial; Animals; Antioxidants; Binge Drinking; Cardiovascular Diseases; Cardiovascular System; Humans; Resveratrol; Stilbenes; Wine

Resveratrol, a naturally occurring phytopolyphenol compound, has attracted extensive interest in recent years because of its diverse pharmacological characteristics. Considering the central role of mitochondria in cell signaling, growth and death, in the present paper we have tried to summarize the present data including patents and discuss the beneficial effects of resveratrol on cardiovascular diseases from the mitochondria perspective.

Topics: Animals; Antioxidants; Cardiovascular Diseases; Cardiovascular System; Drug Delivery Systems; Humans; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mitochondria; Patents as Topic; Resveratrol; Stilbenes

The term FRENCH PARADOX was coined in 1992 to describe the relatively low incidence of cardiovascular disease in the French population, despite a relatively high dietary intake of saturated fats, and potentially attributable to the consumption of red wine. After nearly 20 years, several studies have investigated the fascinating, overwhelmingly positive biological and clinical associations of red wine consumption with cardiovascular disease and mortality. Light to moderate intake of red wine produces a kaleidoscope of potentially beneficial effects that target all phases of the atherosclerotic process, from atherogenesis (early plaque development and growth) to vessel occlusion (flow-mediated dilatation, thrombosis). Such beneficial effects involve cellular signaling mechanisms, interactions at the genomic level, and biochemical modifications of cellular and plasma components. Red wine components, especially alcohol, resveratrol, and other polyphenolic compounds, may decrease oxidative stress, enhance cholesterol efflux from vessel walls (mainly by increasing levels of high-density lipoprotein cholesterol), and inhibit lipoproteins oxidation, macrophage cholesterol accumulation, and foam-cell formation. These components may also increase nitric oxide bioavailability, thereby antagonizing the development of endothelial dysfunction, decrease blood viscosity, improve insulin sensitivity, counteract platelet hyperactivity, inhibit platelet adhesion to fibrinogen-coated surfaces, and decrease plasma levels of von Willebrand factor, fibrinogen, and coagulation factor VII. Light to moderate red wine consumption is also associated with a favorable genetic modulation of fibrinolytic proteins, ultimately increasing the surface-localized endothelial cell fibrinolysis. Overall, therefore, the "French paradox" may have its basis within a milieu containing several key molecules, so that favorable cardiovascular benefits might be primarily attributable to combined, additive, or perhaps synergistic effects of alcohol and other wine components on atherogenesis, coagulation, and fibrinolysis. Conversely, chronic heavy alcohol consumption and binge drinking are associated with increased risk of cardiovascular events. In conclusion, although mounting evidence strongly supports beneficial cardiovascular effects of moderate red wine consumption (one to two drinks per day; 10-30 g alcohol) in most populations, clinical advice to abstainers to initiate daily alcohol consumption h

Topics: Alcohol Drinking; Antioxidants; Atherosclerosis; Blood Pressure; Cardiovascular Diseases; Cholesterol, HDL; Coronary Artery Disease; Endothelium, Vascular; Fibrinolysis; Hemostasis; Humans; Resveratrol; Stilbenes; Wine

Resveratrol (RS), a polyphenol compound found in grapes and grape products, including wine, peanuts and berries, exists in cis- and trans-isomeric forms. RS is believed to decrease circulating low-density lipoprotein cholesterol levels and reduce cardiovascular disease (CVD) risk. However, it is possible that RS has other mechanisms to reduce the risk of CVD without altering lipid levels. The objective of this review is to critically examine results from recent research concerning potential effects of RS on CVD. RS exerts several health benefits including anti-atherogenic, anti-inflammatory and anti-cancer effects. RS may also prevent lipid oxidation, platelet aggregation, arterial vasodilation and modulates the levels of lipids and lipoproteins. As a potent, anti-oxidant RS reduces oxidative stress and regenerates alpha-tocopherol, which further strengthens the anti-oxidant defense mechanism. RS has been considered safe as no significant toxic effects have been identified, even when consumed at higher concentrations. This evidence identified RS as an effective anti-atherogenic agent, which could be used in the prevention and treatment of CVD.

Topics: Animals; Antioxidants; Atherosclerosis; Cardiovascular Diseases; Humans; Lipids; Phytotherapy; Plant Extracts; Resveratrol; Stilbenes; Vitis

Red wine contains many compounds that may have therapeutic use, including resveratrol (3,4',5-trihydroxytrans-stilbene). Since resveratrol could be administered both in the diet and as a therapeutic agent, defining appropriate concentrations requires understanding of the pharmacokinetics. Resveratrol absorption is rapid but plasma concentrations are low as it is rapidly and efficiently converted into relatively hydrophilic phase-2 conjugates, and metabolites, which are then rapidly excreted via the urine and bile. Resveratrol is an effective antioxidant in vivo by increasing NO synthesis and also maintaining the reduced intracellular redox state via the thioredoxin system. Further, activation of sirtuins (one class of lysine deacetylases) may mediate the cardiovascular responses shown by resveratrol. Studies on animal models of human disease suggest that resveratrol has the potential to decrease cardiovascular symptoms in patients with myocardial infarction, arrhythmias, hypertension, cardiomyopathies, fibrosis, atherosclerosis, thrombosis and diabetes, but, as yet, human clinical trials are rare. Cardioprotection by resveratrol in rodent models may rely on mechanisms producing pharmacological preconditioning in the heart including reducing reactive oxygen species, improving vasorelaxation and angiogenesis, preventing inflammation and apoptosis, delaying atherosclerosis as well as decreasing cardiovascular remodelling. Interventional studies in humans need to be completed before resveratrol can be considered as a standard therapeutic agent. Therefore, future studies should focus on obtaining the level of evidence required to determine whether resveratrol can be added to the list of evidence-based therapies for cardiovascular diseases that includes renin-angiotensin system inhibitors, beta-adrenoceptor antagonists and calcium entry blockers.

Topics: Animals; Antioxidants; Cardiovascular Diseases; Cardiovascular System; Humans; Resveratrol; Stilbenes

Topics: Animals; Antioxidants; Cardiovascular Diseases; Evidence-Based Medicine; Humans; Inflammation; Metabolic Syndrome; Neoplasms; Phytotherapy; Protective Agents; Resveratrol; Stilbenes

Resveratrol (3,4',5-trihydroxystilbene) is a member of natural, plant-derived chemicals known as polyphenols and is attracting increased attention due to its diverse health benefits especially in case of cardiovascular disease, cancer, diabetes and neurological problems. Despite impressive gains in diagnosis and treatment, cardiovascular disease (CVD) remains a serious clinical problem and threat to public health. Resveratrol possesses potent antioxidant properties and has been shown to decrease low-density lipoprotein-cholesterol oxidation and platelet aggregation. This compound also possesses a range of additional cardioprotective and vasoprotective properties including antiatherosclerotic and vasorelaxation action. Resveratrol also has the capacity to interact with multiple molecular targets, which involve diverse intracellular pathways. Most well-known is the ability of resveratrol to activate sirtuins, a class of NAD(+)-dependent deacetylase that affect multiple transcription factors and other protein targets. Recently, resveratrol was found to induce autophagy and regenerate myocardial ischemic tissue treated with stem cells. Overall observation indicates that resveratrol has a high therapeutic potentials for the treatment of cardiovascular diseases.

Topics: Animals; Antioxidants; Cardiovascular Diseases; Health Behavior; Humans; Lipoproteins, LDL; Resveratrol; Stilbenes

Plants continuously produce an extraordinary variety of biologically active low-molecular-mass compounds. Among them, resveratrol (3,5,4'-trihydroxystilbene) is endowed with significant positive activities by protecting against cardiovascular diseases and preventing the development and progression of atherosclerosis. Furthermore, the molecule significantly ameliorates glucose homeostasis in obese mice. These beneficial effects have driven considerable interest towards resveratrol molecular activities, and intensive efforts for the identification of the stilbene targets have been made. The molecule shows a pleiotropic mode of action. Particularly, its cellular targets are crucial for cell proliferation and differentiation, apoptosis, antioxidant defence and mitochondrial energy production. The complexity of resveratrol activities might account for its effectiveness in ameliorating multifactorial processes, including the onset and/or progression of several degenerative diseases such as myocardial infarction, atherosclerosis and type 2 diabetes. This article reports the actions of resveratrol on cardiovascular diseases and the molecular bases of its activity. We also discuss recent data on the effect of resveratrol on glucose homeostasis and obesity. Finally, the relevance of the stilbene use in the development of new pharmacological strategies is evaluated.

Topics: Animals; Anti-Inflammatory Agents; Cardiovascular Diseases; Cholesterol; Glucose; Homeostasis; Humans; Macrophages; Myocardial Reperfusion Injury; Platelet Aggregation; Resveratrol; Stilbenes

Longevity can be explained by the free radical theory of aging, and caloric restriction (CR) studies showed that CR-induced lifespan extension is associated with the prevention of a decrease in oxidative stress. Non-enzymatic lipophilic antioxidants may play a pivotal role in our aging process, and are reflected in our dietary lifestyle and dietary supplementation. Their significance lies in their general good absorption and slow excretion within our body. Although difficulties exist with human aging studies due to the nature of our longevity in comparison with other species, findings have implied a relationship between non-enzymatic antioxidants and longevity. Common non-enzymatic antioxidants found in our dietary intake include vitamin A and E supplementation, flavanoids (major source includes tea, one of our main fluid intake), resveratrol (its protective role in cardiovascular disease and aging having stemmed from the "French Paradox"), as well as coenzyme Q₁₀ supplementation. The review discusses current findings and their implication in the aging process. This review concludes by asserting that although none of these antioxidants has yet provided clear-cut evidence toward longevity and the aging process, they have certainly demonstrated other potential health benefits.

Topics: Antioxidants; Cardiovascular Diseases; Diet; Dietary Supplements; Free Radicals; Humans; Life Style; Longevity; Oxidative Stress; Resveratrol; Stilbenes; Ubiquinone; Vitamin A; Vitamin E

The silent information regulator (SIR) genes (sirtuins) comprise a highly conserved family of proteins, with one or more sirtuins present in virtually all species from bacteria to mammals. In mammals seven sirtuin genes - SIRT1 to SIRT7 - have been identified. Emerging from research on the sirtuins is a growing appreciation that the sirtuins are a very complicated biological response system that influences many other regulator molecules and pathways in complex manners. Responses of this system to environmental factors, as well as its role in health and disease, are currently incompletely characterized and at most partially understood. This article reviews the mammalian sirtuin system, discusses the dietary, lifestyle, and environmental factors that influence sirtuin activity, and summarizes research on the importance of vitamin B3 in supporting sirtuin enzyme activity, as well as the role specifically of the amide form of this vitamin - nicotinamide - to inhibit sirtuin enzyme activity. Polyphenols, especially resveratrol, influence sirtuins. Existing evidence on these nutritional compounds, as they relate to the sirtuin system, is reviewed. In Part 2 of this review, clinical situations where sirtuins might play a significant role, including longevity, obesity, fatty liver disease, cardiovascular health, neurological disease, and cancer, are discussed.

Topics: Aging; Biological Availability; Cardiovascular Diseases; Enzyme Activators; Humans; Learning; Longevity; Memory; Neoplasms; Nervous System Diseases; Obesity; Phenols; Resveratrol; Sirtuins; Stilbenes

The silent information regulator (SIR) genes (sirtuins) comprise a highly conserved family of proteins, with one or more sirtuins present in virtually all species from bacteria to mammals. In mammals seven sirtuin genes - SIRT1 to SIRT7 - have been identified. Emerging from research on the sirtuins is a growing appreciation that they are a very complicated biological response system that influences many other regulator molecules and pathways in complex manners. Part 1 of this article provided an overview of the mammalian sirtuin system, discussed the dietary, lifestyle, and environmental factors that influence sirtuin activity, and summarized research on the importance of vitamin B3 in supporting sirtuin enzyme activity, as well as the role specifically of the amide form of this vitamin - nicotinamide - to inhibit sirtuin enzyme activity. In Part 2 of this review, clinical situations where sirtuins might play a significant role, including longevity, obesity, fatty liver disease, cardiovascular health, neurological disease, and cancer are discussed. Research on the ability of nutritional substances, especially resveratrol, to influence sirtuin expression and function, and hence alter the courses of some clinical situations, is also reviewed.

Topics: Aging; Biological Availability; Cardiovascular Diseases; Enzyme Activators; Humans; Longevity; Neoplasms; Nervous System Diseases; Obesity; Phenols; Resveratrol; Sirtuins; Stilbenes

In contrast to many years of important research and clinical attention to the pathological effects of alcohol (ethanol) abuse, the past several decades have seen the publication of a number of peer-reviewed studies indicating the beneficial effects of light-moderate, nonbinge consumption of varied alcoholic beverages, as well as experimental demonstrations that moderate alcohol exposure can initiate typically cytoprotective mechanisms. A considerable body of epidemiology associates moderate alcohol consumption with significantly reduced risks of coronary heart disease and, albeit currently a less robust relationship, cerebrovascular (ischemic) stroke. Experimental studies with experimental rodent models and cultures (cardiac myocytes, endothelial cells) indicate that moderate alcohol exposure can promote anti-inflammatory processes involving adenosine receptors, protein kinase C (PKC), nitric oxide synthase, heat shock proteins, and others which could underlie cardioprotection. Also, brain functional comparisons between older moderate alcohol consumers and nondrinkers have received more recent epidemiological study. In over half of nearly 45 reports since the early 1990s, significantly reduced risks of cognitive loss or dementia in moderate, nonbinge consumers of alcohol (wine, beer, liquor) have been observed, whereas increased risk has been seen only in a few studies. Physiological explanations for the apparent CNS benefits of moderate consumption have invoked alcohol's cardiovascular and/or hematological effects, but there is also experimental evidence that moderate alcohol levels can exert direct "neuroprotective" actions-pertinent are several studies in vivo and rat brain organotypic cultures, in which antecedent or preconditioning exposure to moderate alcohol neuroprotects against ischemia, endotoxin, beta-amyloid, a toxic protein intimately associated with Alzheimer's, or gp120, the neuroinflammatory HIV-1 envelope protein. The alcohol-dependent neuroprotected state appears linked to activation of signal transduction processes potentially involving reactive oxygen species, several key protein kinases, and increased heat shock proteins. Thus to a certain extent, moderate alcohol exposure appears to trigger analogous mild stress-associated, anti-inflammatory mechanisms in the heart, vasculature, and brain that tend to promote cellular survival pathways.

Topics: Alcohol Drinking; Animals; Antioxidants; Cardiotonic Agents; Cardiovascular Diseases; Central Nervous System Depressants; Dementia; Ethanol; Humans; Neuroprotective Agents; Nitric Oxide; Protein Kinase C; Resveratrol; Stilbenes

Resveratrol is a phytoalexin, highly abundant in skins of red grapes and moderately abundant in peanuts and blueberries. Originally a constituent of oriental medicines, it has lately been rediscovered for a plethora of beneficial properties such as anti-cancer, anti-aging, antiviral, cardiovascular and neuroprotective effects, thereby making it one of the most sought after phytochemicals for supplementing human diet. Studies done in various laboratories have shown its modulatory effects on multitudes of cell signaling and gene expression pathways. Although most of its effects have been observed in cultured cells, quite a few have also been validated in whole animals as well. It is thus necessary to have a comprehensive look at all those effects of resveratrol in an organismal context. The following review summarizes the effects of resveratrol in the context of chemoprevention.

Topics: Animals; Anticarcinogenic Agents; Antioxidants; Cardiovascular Diseases; Drug Evaluation, Preclinical; Gene Expression Regulation; Humans; Neoplasms; Neoplasms, Hormone-Dependent; Phytoestrogens; Resveratrol; Signal Transduction; Stilbenes

Resveratrol (3,4',5 trihydroxystilbene), a naturally-occurring molecule known as a phytoalexin, is synthesized by plants in response to attacks by fungi, bacteria, or other injurious substances; it is also known to possess an array of cardioprotective effects. Recently, studies have shown resveratrol to protect against the metabolic changes associated with hypercaloric diets in mice with induced insulin resistance, hyperglycemia, and dyslipidemia. Despite impressive gains in diagnosis and treatment, cardiovascular disease (CVD) remains a serious clinical problem and threat to public health. The metabolic syndrome, which identifies persons at higher risk for diabetes mellitus and CVD, is approaching a prevalence of nearly 25% of the western world. If the metabolic syndrome can be considered a polar opposite to caloric restriction, then agents that mimic caloric restriction may offer a new therapeutic approach to preventing CVD. The authors discuss the cardioprotective effects of resveratrol and highlight its role in glucose homeostasis and lipid metabolism in mice. Armed with the ability to prevent the deleterious effects of excess caloric intake and prevent detrimental cardiovascular events, resveratrol merits proper clinical investigations for its efficacy in treating metabolic diseases and CVD.

Topics: Animals; Blood Glucose; Caloric Restriction; Cardiovascular Agents; Cardiovascular Diseases; Dietary Carbohydrates; Dietary Fats; Energy Intake; Homeostasis; Humans; Lipid Metabolism; Metabolic Syndrome; Molecular Structure; Resveratrol; Sirtuin 1; Sirtuins; Stilbenes

Evidence from animal models and preliminary studies in humans indicates that calorie restriction (CR) delays cardiac aging and can prevent cardiovascular disease. These effects are mediated by a wide spectrum of biochemical and cellular adaptations, including redox homeostasis, mitochondrial function, inflammation, apoptosis, and autophagy. Despite the beneficial effects of CR, its large-scale implementation is challenged by applicability issues as well as health concerns. However, preclinical studies indicate that specific compounds, such as resveratrol, may mimic many of the effects of CR, thus potentially obviating the need for drastic food intake reductions. Results from ongoing clinical trials will reveal whether the intriguing alternative of CR mimetics represents a safe and effective strategy to promote cardiovascular health and delay cardiac aging in humans.

Topics: Aged; Animals; Antioxidants; Apoptosis; Autophagy; Caloric Restriction; Cardiovascular Diseases; Disease Models, Animal; Forecasting; Heart Diseases; Homeostasis; Humans; Inflammation; Inflammation Mediators; Mitochondria, Heart; Mitochondrial Diseases; Obesity; Oxidation-Reduction; Oxidative Stress; Resveratrol; Stilbenes

The metabolic syndrome (MetS) encompasses a constellation of cardio-metabolic abnormalities associated with a high risk of developing type 2 diabetes and cardiovascular disease (CVD), the top killer in the ageing population. Recent studies have demonstrated multiple beneficial effects of moderate wine consumption in the protection against development of the MetS and its related medical complications. The association of moderate wine consumption with lower incidence of the MetS and atherosclerotic heart disease has been repeatedly documented in numerous epidemiological studies on diverse ethnic groups. In addition to the favorable effects of moderate ethanol intake on lipid profiles, polyphenols enriched in red wine possess multiple benefits on the MetS beyond alcohol through their anti-oxidant, anti-inflammatory, vascular-protective and insulin-sensitizing properties. Notable among these red wine polypheolic compounds is resveratrol, a phytoalexin that has recently attracted great attention due to its role in mimicking calorie restriction. This compound can act as a potent activator of the NAD(+)-dependent deacetylases sirtuins to expand the life span and to prevent the deleterious effects of excess intake on insulin resistance and metabolic derangement. In addition, resveratrol exerts its multiple protective effects against the MetS through stimulating AMP-activated protein kinase and promoting mitochondria biogenesis. In this review, we highlight the recent epidemiological and experimental evidences supporting the protective effects of moderate wine intake against the MetS and its associated cardio-metabolic complications, and discuss the molecular mechanisms underlying the multiple beneficial actions of red wine polyphenols with the focus on resveratrol.

Topics: Alcohol Drinking; Animals; Antioxidants; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Insulin Resistance; Metabolic Syndrome; Randomized Controlled Trials as Topic; Resveratrol; Stilbenes; Wine

Studies show that the plant polyphenol resveratrol can extend the life span of yeast, worms, flies, and fish. It also mitigates the metabolic dysfunction of mice fed high-fat diets. Resveratrol appears to mediate these effects partly by activating SIRT1, a deacetylase enzyme that regulates the activity of several transcriptional factors and enzymes responsive to nutrient availability. However, few foods contain resveratrol and humans metabolize it extensively, resulting in very low systemic bioavailability. Substantial research effort now focuses on identifying and testing more bioavailable and potent activators of SIRT1 for use as pharmacologic interventions in aging and age-related disorders.

Topics: Aging; Animals; Biological Availability; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Enzyme Activation; Enzyme Activators; Humans; Inflammation; Neurodegenerative Diseases; Resveratrol; Sirtuin 1; Sirtuins; Stilbenes

The aim of this review is to discuss the accumulating evidence that suggests that grape extracts and purified grape polyphenols possess a diverse array of biological actions and may be beneficial in the prevention of some inflammatory-mediated diseases including cardiovascular disease. The active components from grape extracts, which include the grape seed, grape skin, and grape juice, that have been identified thus far include polyphenols such as resveratrol, phenolic acids, anthocyanins, and flavonoids. All possess potent antioxidant properties and have been shown to decrease low-density lipoprotein-cholesterol oxidation and platelet aggregation. These compounds also possess a range of additional cardioprotective and vasoprotective properties including antiatherosclerotic, antiarrhythmic, and vasorelaxation actions. Although not exclusive, antioxidant properties of grape polyphenols are likely to be central to their mechanism(s) of action, which also include cellular signaling mechanisms and interactions at the genomic level. This review discusses some of the evidence favoring the consumption of grape extracts rich in polyphenols in the prevention of cardiovascular disease. Consumption of grape and grape extracts and/or grape products such as red wine may be beneficial in preventing the development of chronic degenerative diseases such as cardiovascular disease.

Topics: Antioxidants; Cardiovascular Diseases; Flavonoids; Fruit; Humans; Inflammation; Oxidative Stress; Phenols; Phytotherapy; Plant Preparations; Platelet Aggregation; Polyphenols; Resveratrol; Seeds; Stilbenes; Vasodilation; Vitis; Wine

Previous studies have shown that consumption of fruit and vegetables plays a role in preventing the onset of CVD. These beneficial effects have been linked to the presence of polyphenolic compounds in plant-derived foods and their antioxidant capacity. It has been hypothesised that polyphenols may also have a direct effect on vascular endothelial cell growth and the expression of genes involved in angiogenesis and other roles of the endothelium. Previous studies in this area have tended to use concentrations of polyphenols that are supraphysiological (1-100 microm). The effects of more physiological concentrations (0.1 microm) of various individual polyphenols on gene expression were therefore investigated in cultured human umbilical vein endothelial cells (HUVEC) using both microarray and quantitative RT-PCR methodologies. Treatment of HUVEC with ferulic acid, quercetin or resveratrol (0.1 microm) resulted in changes to gene expression that for the three treatments amounted to significant (>2-fold) down-regulation of the expression of 363 genes and significant (>2-fold) up-regulation of 233 genes of the 10 000 genes present on the microarray. The majority of these genes were affected by resveratrol. Quantitative RT-PCR studies indicated that resveratrol (0.1 microm) significantly increased the expression of the gene encoding endothelial NO synthase (eNOS), which synthesises the vasodilator molecule NO, and both resveratrol and quercetin decreased expression of the potent vasoconstrictor, endothelin-1 (ET-1), while ferulic acid had no effect. The effects of resveratrol (0.1 microm) were also investigated when HUVEC were under oxidative stress following treatment with H2O2 (0-50 microm), which dose-dependently increased expression of eNOS and ET-1. Resveratrol stimulated eNOS mRNA in the absence of H2O2 and still allowed the increase with H2O2, but the effects were not additive. In contrast, resveratrol blocked the stimulatory effect of H2O2 on ET-1 expression. Hence, resveratrol has potent effects at a physiological concentration (0.1 microm) that would be expected to result in vasodilation and therefore help reduce blood pressure and the risk of CVD.

Topics: Cardiovascular Diseases; Cells, Cultured; Dose-Response Relationship, Drug; Endothelial Cells; Endothelin-1; Endothelium, Vascular; Flavonoids; Gene Expression Profiling; Gene Expression Regulation; Humans; Nitric Oxide Synthase; Oligonucleotide Array Sequence Analysis; Phenols; Polyphenols; Resveratrol; Reverse Transcriptase Polymerase Chain Reaction; Stilbenes; Umbilical Veins

Observational studies suggest nut consumption is inversely associated with the incidence of cardiovascular disease and cancer. In addition to being rich in several vitamins and minerals, unsaturated fatty acids, and fiber, tree nuts and peanuts contain numerous phytochemicals that may contribute to promoting health and reducing the risk of chronic disease. While many of these bioactive constituents remain to be fully identified and characterized, broad classes include carotenoids, phenols, and phytosterols. Phytosterols in nuts range from 95-280 mg/100 g. alpha- and beta-Carotene, beta-cryptoxanthin, lutein, and zeaxanthin are found in microg/100 g amounts in some nuts but at 1-3 mg/100 g in pistachios and none at all in Brazils, macadamias, and peanuts. Phenols, including phenolic acids, flavonoids, and stilbenes, are present in nuts. Walnuts are particularly rich in total phenols with 1625 mg gallic acid equivalents/100 g. The stilbene resveratrol is found in peanuts and pistachios at 84 and 115 microg/100 g, respectively. The flavonoid content of nuts as provided in USDA Database for the Flavonoid Content of Selected Foods, lists totals in pecans at 34, almonds at 15, and pistachios and hazelnuts at 12 mg/100 g. Proanthocyanidins are found in almonds, cashews, hazelnuts, pecans, pistachios, peanuts, and walnuts, with concentrations varying from 9-494 mg/100 g. Nut phytochemicals have been associated with numerous bioactivities known to affect the initiation and progression of several pathogenic processes. However, as complete phytochemical profiles are lacking for most nuts, information is limited regarding their bioavailability and metabolism, so further research on this topic is warranted.

Topics: Antioxidants; Cardiovascular Diseases; Flavonoids; Food, Organic; Humans; Neoplasms; Nuts; Phenols; Seeds; Stilbenes

The results of studies on the role of appropriate wine consumption in the prevention of cardiovascular disease are inconsistent, suggesting that the general approach to the issue needs to be revisited before further research is conducted. A number of points for consideration are raised: (1) the necessity to characterize wine analytically, as the content in important components of wine, such as resveratrol, is influenced considerably by regional factors, such as climate and local oenological procedures; (2) the bioavailability of the components of wine, which appears to be adequate as a broad range of biological effects have been documented at low concentrations that can be achieved by moderate chronic wine consumption; (3) the lack of importance of wine color, as also white wine consumption affords benefit, thanks to its content in the antioxidants caffeic acid, tyrosol and hydroxytyrosol, which are also found in olive oil; (4) the recommendation by WHO to "investigate the possible protective effects of ingredients other than alcohol in alcoholic beverages".

Topics: Animals; Antioxidants; Cardiovascular Diseases; Dose-Response Relationship, Drug; Humans; Plant Extracts; Rats; Research Design; Resveratrol; Stilbenes; Wine

Resveratrol, a polyphenol found in numerous plant species, including mulberries, peanuts and grapes, has shown to possess chemopreventive properties against several cancers, and cardiovascular diseases. Recently, resveratrol has been shown to have positive effects on age longevity, lipid levels and a preventative quality against certain cancers and viral infections. Resveratrol induces apoptosis by up-regulating the expression of Bax, Bak, PUMA, Noxa, Bim, p53, TRAIL, TRAIL-R1/DR4 and TRAIL-R2/DR5 and simultaneously down-regulating the expression of Bcl-2, Bcl-XL, Mcl-1 and survivin. Resveratrol causes growth arrest at G1 and G1/S phases of cell cycle by inducing the expression of CDK inhibitors p21/WAF1/CIP1 and p27/KIP1. Resveratrol has also been shown to reduce inflammation via inhibition of prostaglandin production, cyclooxygenase-2 activity, and nuclear factor-kappaB activity. Modulation of cell signaling pathway by resveratrol explains its diverse bioactivities related with human health. Resveratrol also potentiates the apoptotic effects of cytokines, chemotherapeutic agents and gamma-radiation. Pharmacokinetic and pharmacodynamic studies demonstrated that the main target organs of resveratrol are liver and kidney, and it is metabolized by hydroxylation, glucuronidation, sulfation and hydrogenation. As a chemoprevention agent, resveratrol has been shown to inhibit tumor initiation, promotion, and progression. There is growing evidence that resveratrol can prevent or delay the onset of various cancers, heart diseases, ischemic and chemically induced injuries, pathological inflammation and viral infections. This review summarizes the molecular mechanisms of resveratrol and its clinical benefits for human diseases.

Topics: Cardiovascular Diseases; Cell Cycle; Chemoprevention; Chemotherapy, Adjuvant; Diabetes Mellitus; Gene Expression Regulation; Humans; Inflammation; Neoplasms; Neovascularization, Pathologic; Resveratrol; Signal Transduction; Stilbenes

Resveratrol is a phytoalexin produced by many plants, and the skin of red grapes is particularly rich in resveratrol which accounts for the "French Paradox". Besides its protection of the cardiovascular system, it can affect the processes underlying all three stages of carcinogenesis, involving tumor initiation, promotion and progression. It has also been shown to suppress angiogenesis and metastasis. The anti-carcinogenic effects of resveratrol appear to be closely associated with its capacity to interact with multiple molecular targets involved in cancer development, while minimizing toxicity in normal tissues as tested. By reviewing many in vitro and in vivo studies, also considering both the supporting and challenging evidences, we are provided with a theory in support of the use of resveratrol in human cancer chemoprevention, in combination with either chemotherapeutic drugs or cytotoxic factors for the highly efficient treatment of drug refractory tumor cells. Anti-carcinogenic potential for cancer chemoprevention and anticancer therapy, which is one of the pleiotropic effects of resveratrol, is so called a new enlightenment of French Paradox.

Topics: Animals; Anticarcinogenic Agents; Antioxidants; Cardiovascular Diseases; Cell Line, Tumor; Cell Transformation, Neoplastic; Clinical Trials as Topic; Diet; Europe; France; Gene Expression Regulation, Neoplastic; Humans; Incidence; Mice; Mice, Inbred A; Neoplasms; Resveratrol; Stilbenes; Wine

The heart is an aerobic organ, and most of the energy required for the contraction and maintenance of ion gradients comes from oxidative phosphorylation. Oxidative stress caused by free radicals plays a crucial role in the pathophysiology associated with atherosclerosis, neoplasia and neurodegenerative diseases. Therefore, a great deal of attention has focused on the naturally occurring antioxidant phytochemicals as potential therapy for cardiovascular diseases. One of the most recognized and widely studied compounds is resveratrol, a member of a family of polyphenols called viniferins. Although resveratrol was first isolated in 1940 from the roots of white hellebore (Veratrum grandiflorum), the importance of resveratrol was recognized only after the widely publicized historic "French Paradox" associated with drinking of red wine. Both epidemiological and experimental studies have revealed that drinking wine, particularly red wine, in moderation protects cardiovascular health; however, the experimental basis for such an action is not fully understood. A growing body of evidence supports the role of resveratrol as evidence based cardiovascular medicine. Resveratrol protects the cardiovascular system by multidimensional way. The most important point about resveratrol is that at a very low concentration, it inhibits apoptotic cell death, thereby providing protection from various diseases including myocardial ischemic reperfusion injury, atherosclerosis and ventricular arrhythmias. Both in acute and in chronic models, resveratrol-mediated cardioprotection is achieved through the preconditioning effect (the state-of-the-art technique of cardioprotection), rather than direct effect as found in conventional medicine. The same resveratrol when used in higher doses, it facilitates apoptotic cell death, and behaves as a chemo-preventive alternative. Resveratrol likely fulfills the definition of a pharmacological preconditioning compound and gives hope for the therapeutic promise of alternative medicine. The purpose of this review is to provide evidence in favor of resveratrol to be used as a preventive medicine and related patents for the maintenance of healthy heart.

Topics: Antioxidants; Cardiovascular Diseases; Flavonoids; Models, Biological; Molecular Structure; Phenols; Polyphenols; Reactive Oxygen Species; Resveratrol; Stilbenes; Wine

Numerous epidemiological studies indicate that a moderate intake of alcohol is associated with a reduced risk of morbidity and mortality secondary to cardiovascular diseases. Alcohol intake from any type of alcoholic beverage appears beneficial, but red wine seems to confer additional health benefits because of the presence of red wine polyphenolic compounds (RWPC). On the basis of clinical and experimental data, the favourable effect of moderate intake of alcohol results to its action on lipid profile, hemostatic parameters, and reduction of inflammation markers. RWPC exert numerous effects including antioxidant and free radical properties, anti-aggregatory platelet and anti-thrombotic activities. Moreover, RWPC are powerful vasodilators and contribute to the preservation of the integrity of the endothelium and inhibition of smooth muscle cell proliferation and migration. All these effects of red wine might interfere with atherosclerotic plaque development and stability, vascular thrombosis and occlusion. Although, red wine might be of therapeutic benefit in cardiovascular diseases, prospective controlled clinical studies are still lacking.

Topics: Alcohol Drinking; Animals; Aorta; Atherosclerosis; Cardiovascular Diseases; Color; Endothelium, Vascular; Flavonoids; Humans; Models, Animal; Phenols; Polyphenols; Resveratrol; Risk Assessment; Stilbenes; Thrombosis; Vascular Diseases; Vasodilator Agents; Wine

Epidemiological studies demonstrated that even in the absence of other risk factors (e.g. diabetes, hypertension, hyperhomocysteinemia, hypercholesterolemia), advanced age itself significantly increases cardiovascular morbidity by enhancing vascular oxidative stress and inflammation. Because the population in the Western world is rapidly aging, there is a substantial need for pharmacological interventions that delay the functional decline of the cardiovascular system. Resveratrol is an atoxic phytoestrogen found in more than 70 plants including grapevine and berries. Recent data suggest that nutritional intake of resveratrol and other polyphenol compounds may contribute to the "French paradox", the unexpectedly low cardiovascular morbidity in the Mediterranean population. There is increasing evidence that resveratrol exerts multifaceted anti-oxidant and/or anti-inflammatory effects in various disease models. Importantly, resveratrol was reported to slow aging and increase lifespan in simple organisms and has been suggested as a potential calorie restriction mimetic. Resveratrol has also been reported to activate NAD-dependent histone deacetylases (sirtuins), which may contribute to its anti-aging effects. This review focuses on the role of oxidative stress and inflammation in cardiovascular dysfunction in aging, and on emerging anti-aging therapeutic strategies offered by resveratrol and other polyphenol compounds.

Topics: Aging; Anti-Inflammatory Agents, Non-Steroidal; Cardiovascular Diseases; Humans; Resveratrol; Stilbenes; Vasodilator Agents

Anthracyclines are a well-known cause of cardiotoxicity, but a number of other drugs used to treat cancer can also result in cardiac and cardiovascular adverse effects. Cardiotoxicity can result in the alteration of cardiac rhythm, changes in blood pressure and ischemia, and can also alter the ability of the heart to contract and/or relax. The clinical spectrum of these toxicities can range from subclinical abnormalities to catastrophic life-threatening, and sometimes fatal, sequelae. These events may occur acutely or may only become apparent months or years following completion of oncological treatment. Ischemia and rhythm abnormalities are treated symptomatically in most cases. Knowledge of these toxicities can aid clinicians to choose the optimal and least toxic regimen suitable for an individual patient.

Topics: Anthracyclines; Antineoplastic Agents; Arsenic Trioxide; Arsenicals; Cardiovascular Diseases; Heart Diseases; Humans; Interferons; Interleukin-2; Neoplasms; Oxides; Stilbenes; Tretinoin

Cardiovascular diseases are the leading cause of death in developed countries where the common pathological substrate underlying this process is atherosclerosis. Several new concepts have emerged in relation to mechanisms that contribute to the regulation of the vascular diseases and associated inflammatory effects. Recently, potential antioxidants (vitamin E, polyphenols) have received much attention as potential anti-atherosclerotic agents. Among the polyphenols with health benefic properties, resveratrol, a phytoalexin of grape, seem to be a good candidate protecting the vascular walls from oxidation, inflammation, platelet aggregation, and thrombus formation. In this review, we focus on the mechanism of resveratrol cardiovascular benefic effects. We analyze, in relation with the different steps of atherosclerotic process, the resveratrol properties at multiple levels, such as cellular signaling, enzymatic pathways, apoptosis, and gene expression. We show and discuss the relationship with reactive oxygen species, regulation of pro-inflammatory genes including cycloxygenases and cytokines in molecular inflammatory and aging processes, and how the regulation of these activites by resveratrol can lead to a prevention of vascular diseases.

Topics: Aging; Arteriosclerosis; Cardiovascular Diseases; Foam Cells; Health Promotion; Humans; Lipoproteins; Macrophages; Muscle, Smooth, Vascular; Neovascularization, Pathologic; Oxidative Stress; Platelet Aggregation; Resveratrol; Stilbenes; Vasodilation

The interest in the potential health effects of dietary phytoestrogens has increased with the findings that hormone replacement therapy is not as safe or effective as previously thought. This review summarizes the dietary sources of the phytoestrogens; isoflavonoids, stilbenes, coumestans and lignans. It also examines 105 clinical studies related to effects of phytoestrogens on bone density, cardiovascular health, cancer prevention, cognitive ability and menopausal symptoms.

Topics: Animals; Bone Density; Cardiovascular Diseases; Clinical Trials as Topic; Cognition; Diet; Humans; Isoflavones; Lignans; Menopause; Phytoestrogens; Plant Preparations; Stilbenes

The phytoantitoxin resveratrol is a plant-derived polyphenol with phytoestrogenic properties. Resveratrol protects the cardiovascular system by mechanisms that include defense against ischemic-reperfusion injury, promotion of vasorelaxation, protection and maintenance of intact endothelium, anti-atherosclerotic properties, inhibition of low-density lipoprotein oxidation, suppression of platelet aggregation, and estrogen-like actions. The purpose of this article is to review the mechanisms of these effects.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents, Phytogenic; Antioxidants; Cardiovascular Agents; Cardiovascular Diseases; Cell Division; Humans; Phytoestrogens; Resveratrol; Signal Transduction; Stilbenes

Resveratrol (3,4',5-trihydroxy-trans-stilbene), a phytoalexin found in grape skins, peanuts, and red wine, has been reported to have a wide range of biological and pharmacological properties. It has been speculated that at low doses (such as consumed in the common diet) resveratrol may have cardioprotective activity. In this article we describe recent in vitro and in vivo studies in animal models. The results of these studies suggest that resveratrol modulates vascular cell function, inhibits LDL oxidation, suppresses platelet aggregation and reduces myocardial damage during ischemia-reperfusion. Although the reported biological data indicate that resveratrol is a highly promising cardiovascular protective agent, more studies are needed to establish its bioavailability and in vivo cardioprotective effects, particularly in humans.

Topics: Animals; Antioxidants; Cardiotonic Agents; Cardiovascular Diseases; Cholesterol; Dose-Response Relationship, Drug; Humans; Lipid Peroxidation; Myocardial Reperfusion Injury; Platelet Aggregation Inhibitors; Resveratrol; Stilbenes; Time Factors

Phytoantitoxin resveratrol, which belongs to polyphenol, is a kind of phytoestrogen, and protects the cardiovascular system against ischemic-reperfusion injury and promotion of vasorelaxation, protects and maintains the intact endothelium, exhibits antiatherosclerotic properties inhibits the LDL oxidation, suppress the platelet aggregation and exhibits estrogen like action. The purpose of this article is to review the mechanisms of about mentioned effects. (Ref. 30.).

Topics: Animals; Cardiovascular Diseases; Humans; Protective Agents; Resveratrol; Stilbenes

This review reconsiders a major cause of cardiovascular diseases, tobacco smoking, as the activation of the Aryl hydrocarbon Receptor (AhR), also known as the dioxin receptor, by aryl hydrocarbons from the tar fraction of tobacco in various organs of the cardiovascular domain. This concept sheds new light on well-known albeit controversial epidemiological concepts such as the Mediterranean diet and the French paradox. We also review the discovery that resveratrol, a natural AhR antagonist, may be of interest in the prevention and treatment of cardiovascular diseases.

Topics: Cardiovascular Diseases; Humans; Ligands; Nicotiana; Receptors, Aryl Hydrocarbon; Resveratrol; Smoking; Stilbenes; Xenobiotics

"Bioactive compounds" are extranutritional constituents that typically occur in small quantities in foods. They are being intensively studied to evaluate their effects on health. The impetus sparking this scientific inquiry was the result of many epidemiologic studies that have shown protective effects of plant-based diets on cardiovascular disease (CVD) and cancer. Many bioactive compounds have been discovered. These compounds vary widely in chemical structure and function and are grouped accordingly. Phenolic compounds, including their subcategory, flavonoids, are present in all plants and have been studied extensively in cereals, legumes, nuts, olive oil, vegetables, fruits, tea, and red wine. Many phenolic compounds have antioxidant properties, and some studies have demonstrated favorable effects on thrombosis and tumorogenesis and promotion. Although some epidemiologic studies have reported protective associations between flavonoids or other phenolics and CVD and cancer, other studies have not found these associations. Various phytoestrogens are present in soy, but also in flaxseed oil, whole grains, fruits, and vegetables. They have antioxidant properties, and some studies demonstrated favorable effects on other CVD risk factors, and in animal and cell culture models of cancer. However, because phytoestrogens act both as partial estrogen agonists and antagonists, their effects on cancer are likely complex. Hydroxytyrosol, one of many phenolics in olives and olive oil, is a potent antioxidant. Resveratrol, found in nuts and red wine, has antioxidant, antithrombotic, and anti-inflammatory properties, and inhibits carcinogenesis. Lycopene, a potent antioxidant carotenoid in tomatoes and other fruits, is thought to protect against prostate and other cancers, and inhibits tumor cell growth in animals. Organosulfur compounds in garlic and onions, isothiocyanates in cruciferous vegetables, and monoterpenes in citrus fruits, cherries, and herbs have anticarcinogenic actions in experimental models, as well as cardioprotective effects. In summary, numerous bioactive compounds appear to have beneficial health effects. Much scientific research needs to be conducted before we can begin to make science-based dietary recommendations. Despite this, there is sufficient evidence to recommend consuming food sources rich in bioactive compounds. From a practical perspective, this translates to recommending a diet rich in a variety of fruits, vegetables, whole grains, le

Topics: Antioxidants; Cardiovascular Diseases; Carotenoids; Chronic Disease; Dietary Fiber; Estrogens, Non-Steroidal; Food; Humans; Isoflavones; Isothiocyanates; Lycopene; Monoterpenes; Neoplasms; Olive Oil; Phenols; Phytoestrogens; Phytosterols; Plant Oils; Plant Preparations; Resveratrol; Stilbenes; Tea

The polyphenolic phytoalexin resveratrol (3,5,4'- trihydroxy-trans-stilbene) is produced, perhaps primarily, as a natural fungicide by more than 70 plant species, and can be found in high to moderate quantities in various foods including grapes, peanuts and wine. Recent in vitro and a limited number of in vivo studies have documented that physiological concentrations of resveratrol can modulate multiple molecular pathways thought to be associated with the development and progression of cardiovascular disease and cancer, among them phase II drug metabolizing, cyclooxygenase, lipid metabolizing, nitric oxide, DNA-synthesis, inflammation, cell survival, cell death and cell division cycle pathways. Work on the mechanisms underlying the cytostatic activities, which appear to affect all dividing tissues, and the cytotoxic activities of the compound, which seem to preferentially target tumor cells, has produced some controversial and, at times, seemingly conflicting results. The present review attempts to integrate some of the established biochemical activities of resveratrol into a common framework of function in an attempt to understand precisely how the compound affects cell proliferation and survival.

Topics: Animals; Antineoplastic Agents, Phytogenic; Cardiovascular Diseases; Humans; Neoplasms; Resveratrol; Stilbenes

Resveratrol is a phytoalexin found in many plants, mainly in grapes. It has been shown to prevent coronary heart diseases and to exert a variety of anti-cancer and anti-inflammatory effects.

Topics: Animals; Anticarcinogenic Agents; Antioxidants; Cardiovascular Diseases; Humans; Inflammation; Neoplasms; Resveratrol; Ribonucleotide Reductases; Stilbenes

Resveratrol (trans-3,4',5-trihydroxystibene) is a phytopolyphenol isolated from the seeds and skins of grapes. Recent studies indicate that resveratrol can block the process of multistep carcinogenesis, namely, tumor initiation, promotion and progression. Resveratrol can also reduce the risk of cardiovascular disease in man. The molecular mechanisms of resveratrol in chemoprevention of cancer and cardiovascular disease are interesting and under intensive investigation. Resveratrol was found to strongly inhibit nitric oxide (NO) generation in activated macrophages, as measured by the amount of nitrite released into the culture medium, and resveratrol strongly reduced the amount of cytosolic inducible nitric oxide synthase (iNOS) protein. The activation of nuclear factor kappa B (NF kappa B) induced by lipopolysaccharide (LPS) was inhibited by resveratrol. The phosphorylation and degradation of nuclear factor inhibitor kappa B alpha (I kappa B alpha) were inhibited by resveratrol simultaneously. Reactive oxygen species (ROS) are regarded as having carcinogenic potential and have been associated with tumor promotion. Resveratrol may act as a reactive oxygen species scavenger to suppress tumor development. In addition, resveratrol may block multistep carcinogenesis through mitotic signal transduction blockade. Reactive oxygen species are pivotal factors in the genesis of heart disease. Meanwhile, efficient endogenous antioxidants, including superoxide dismutase (SOD), glutathione peroxidase (GSHPx), and catalase, are present in tissues. A fine balance between reactive oxygen species and endogenous antioxidants is believed to exist. Any disturbance of this balance in favor of reactive oxygen species causes an increase in oxidative stress and initiates subcellular changes, leading to cardiomyopathy and heart failure. The experimental results indicate that exogenous antioxidant resveratrol is of value in chemopreventing the development of heart disease. It is urgent that more efforts be made to investigate newer therapies employing antioxidants for the chemoprevention of cardiovascular disease and cancer.

Topics: Anticarcinogenic Agents; Carcinogens; Cardiovascular Diseases; Cell Cycle; Cyclin D1; Enzyme Inhibitors; Gene Expression Regulation; Growth Substances; Humans; Lipid Peroxidation; Neoplasms; NF-kappa B; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Oxidative Stress; Phosphorylation; Protein Processing, Post-Translational; Reactive Oxygen Species; Receptor Protein-Tyrosine Kinases; Resveratrol; Risk Factors; Rosales; Signal Transduction; Stilbenes; Transcription, Genetic; Wine

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

Topics: Adult; Aged; Antioxidants; Blood Glucose; Cardiovascular Diseases; Cholesterol; Dietary Supplements; Double-Blind Method; Humans; Male; Middle Aged; Plant Extracts; Resveratrol; Risk Factors; Schizophrenia; Stilbenes; Triglycerides; Young Adult

In vitro and animal studies have shown positive effects of resveratrol on lipid and lipoprotein metabolism, but human studies specifically designed to examine these effects are lacking.. The primary outcome parameter of this study in overweight and slightly obese subjects was the effect of resveratrol on apoA-I concentrations. Secondary outcome parameters were effects on other markers of lipid and lipoprotein metabolism, glucose metabolism, and markers for inflammation and endothelial function.. This randomized, placebo-controlled crossover study was conducted in 45 overweight and slightly obese men (n = 25) and women (n = 20) with a mean age of 61 ± 7 years. Subjects received in random order resveratrol (150 mg per day) or placebo capsules for 4 weeks, separated by a 4-week wash-out period. Fasting blood samples were collected at baseline and at the end of each intervention period.. Compliance was excellent as indicated by capsule count and changes in resveratrol and dihydroresveratrol concentrations. No difference between resveratrol and placebo was found in any of the fasting serum or plasma metabolic risk markers (mean ± SD for differences between day 28 values of resveratrol vs. placebo: apoA-I; 0.00 ± 0.12 g/L (P = 0.791), apoB100; -0.01 ± 0.11 g/L (P = 0.545), HDL cholesterol; 0.00 ± 0.09 mmol/L (P = 0.721), LDL cholesterol -0.03 ± 0.57 mmol/L (P = 0.718), triacylglycerol; 0.10 ± 0.54 mmol/L (P = 0.687), glucose; -0.08 ± 0.28 mmol/L (P = 0.064), insulin; -0.3 ± 2.5 mU/L (P = 0.516)). Also, no effects on plasma markers for inflammation and endothelial function were observed. No adverse events related to resveratrol intake were observed.. 150 mg of daily resveratrol intake for 4 weeks does not change metabolic risk markers related to cardiovascular health in overweight and slightly obese men and women. Effects on glucose metabolism warrant further study.. ClinicalTrials.gov NCT01364961.

Topics: Aged; Apolipoprotein A-I; Biomarkers; Cardiovascular Diseases; Cross-Over Studies; Female; Humans; Lipid Metabolism; Lipoproteins; Male; Middle Aged; Obesity; Overweight; Resveratrol; Stilbenes

Non-alcoholic fatty liver disease (NAFLD) is usually associated with insulin resistance, central obesity, reduced glucose tolerance, type 2 diabetes mellitus and hypertriacylglycerolaemia. The beneficial effects of resveratrol on metabolic disorders have been shown previously. The aim of this study was to evaluate the effects of resveratrol supplementation on cardiovascular risk factors in patients with NAFLD. In this randomised double-blinded placebo-controlled clinical trial, fifty NAFLD patients were supplemented with either a 500-mg resveratrol capsule or a placebo capsule for 12 weeks. Both groups were advised to follow an energy-balanced diet and physical activity recommendations. resveratrol supplementation reduced alanine aminotransferase (ALT) and hepatic steatosis significantly more than placebo (P0·05). There were no significant changes in blood pressure, insulin resistance markers and TAG in either group (P>0·05). Our data have shown that 12-week supplementation of 500 mg resveratrol does not have any beneficial effect on anthropometric measurements, insulin resistance markers, lipid profile and blood pressure; however, it reduced ALT and hepatic steatosis in patients with NAFLD.

Topics: Adult; Alanine Transaminase; Anti-Inflammatory Agents; Antioxidants; Biomarkers; Blood Pressure; Cardiovascular Diseases; Dietary Supplements; Double-Blind Method; Fatty Liver; Female; Humans; Insulin Resistance; Lipid Metabolism; Liver; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Phytotherapy; Plant Extracts; Resveratrol; Risk Factors; Stilbenes; Triglycerides

Resveratrol, a polyphenol found in grapes, red wine, chocolate, and certain berries and roots, is considered to have antioxidant, anti-inflammatory, and anticancer effects in humans and is related to longevity in some lower organisms.. To determine whether resveratrol levels achieved with diet are associated with inflammation, cancer, cardiovascular disease, and mortality in humans.. Prospective cohort study, the Invecchiare in Chianti (InCHIANTI) Study ("Aging in the Chianti Region"), 1998 to 2009 conducted in 2 villages in the Chianti area in a population-based sample of 783 community-dwelling men and women 65 years or older.. Twenty-four-hour urinary resveratrol metabolites.. Primary outcome measure was all-cause mortality. Secondary outcomes were markers of inflammation (serum C-reactive protein [CRP], interleukin [IL]-6, IL-1β, and tumor necrosis factor [TNF]) and prevalent and incident cancer and cardiovascular disease.. Mean (95% CI) log total urinary resveratrol metabolite concentrations were 7.08 (6.69-7.48) nmol/g of creatinine. During 9 years of follow-up, 268 (34.3%) of the participants died. From the lowest to the highest quartile of baseline total urinary resveratrol metabolites, the proportion of participants who died from all causes was 34.4%, 31.6%, 33.5%, and 37.4%, respectively (P = .67). Participants in the lowest quartile had a hazards ratio for mortality of 0.80 (95% CI, 0.54-1.17) compared with those in the highest quartile of total urinary resveratrol in a multivariable Cox proportional hazards model that adjusted for potential confounders. Resveratrol levels were not significantly associated with serum CRP, IL-6, IL-1β, TNF, prevalent or incident cardiovascular disease, or cancer.. In older community-dwelling adults, total urinary resveratrol metabolite concentration was not associated with inflammatory markers, cardiovascular disease, or cancer or predictive of all-cause mortality. Resveratrol levels achieved with a Western diet did not have a substantial influence on health status and mortality risk of the population in this study.

Topics: Aged; Cardiovascular Diseases; Cohort Studies; Female; Humans; Incidence; Inflammation; Italy; Male; Mortality; Neoplasms; Prevalence; Prospective Studies; Resveratrol; Stilbenes

It has been suggested that arterial stiffness is one of the most important risk factors for the development of a cardiac infarction or stroke. As cardiovascular disease remains the number one killer of individuals before the age of 75, the early detection of cardiovascular disease and its prevention remains paramount in order to sustain a healthy longevity. This article looks at the latest noninvasive technology that can measure arterial stiffness quickly and easily and also highlights a small open trial in which supplements were used to determine their efficacy in helping to reverse/improve arterial stiffness.

Topics: Adult; Aged; Aging; Arginine; Cardiovascular Diseases; Carnosine; Dietary Supplements; Female; Glycation End Products, Advanced; Guanidines; Humans; Male; Middle Aged; Pulse Wave Analysis; Resveratrol; Risk Factors; Stilbenes; Vascular Stiffness

Smokers are characterized by a low-grade systemic inflammatory state and an oxidant-antioxidant imbalance. Few human studies were conducted on the effects of resveratrol, a natural compound with anti-inflammatory and antioxidant properties, and no trial on smokers has been performed to date. We evaluated whether resveratrol has beneficial effects on markers of inflammation and oxidative stress in smokers.. A randomized, double- blind, cross-over trial was performed in 50 healthy adult smokers: 25 were randomly allocated to "resveratrol-first" (30-days: 500mg resveratrol/day, 30-days wash-out, 30-days placebo) and 25 to "placebo-first" (30-days placebo, 30-days wash-out, 30-days 500mg resveratrol/day). Resveratrol significantly reduced C-reactive protein (CRP) and triglyceride concentrations, and increased Total Antioxidant Status (TAS) values. After analyzing data with general linear models to assess period and carry-over effects, the ratios of the values after resveratrol to those after placebo were respectively: 0.47 (95%CI 0.38-0.59) -CRP- and 0.71 (95%CI 0.65-0.78) -triglycerides-, while TAS increased by 74.2 μmol/L (95%CI 60.8-87.6). Uric acid, glucose, insulin, cholesterol, liver enzyme concentrations, and weight, waist circumference, and blood pressure values did not significantly change after resveratrol supplementation.. Because resveratrol has anti-inflammatory, anti-oxidant, and hypotriglyceridemic effects, its supplementation may beneficially affect the increased cardiovascular risk of healthy smokers.

Topics: Adult; Anti-Inflammatory Agents; Antioxidants; C-Reactive Protein; Cardiovascular Diseases; Cross-Over Studies; Dietary Supplements; Double-Blind Method; Female; Humans; Inflammation; Male; Middle Aged; Oxidative Stress; Placebo Effect; Resveratrol; Risk Factors; Smoking; Stilbenes; Triglycerides

Moderate wine consumption has been shown to reduce cardiovascular (CV) risk, due to alcohol and polyphenolic compounds, such as resveratrol. We investigated the associations between total urinary resveratrol metabolites (TRMs) as biomarkers of wine and resveratrol consumption and CV risk factors in a large cross-sectional study including high CV risk individuals in Spain. We studied 1000 participants in the PREDIMED Study in whom TRMs were analyzed by LC-MS/MS with a previous solid phase extraction. Multiple linear regression of TRMs (biomarker of wine consumption) improved the mean (95% CI) of HDL [0.168 (0.027-0.309); P=0.02] and triglyceride [-1.012 (-1.797 to -0.227); P=0.012] plasma concentrations and heart rate [-0.259 (-0.412 to -0.107); P<0.001]. Models of TRMs adjusted for alcohol (biomarker of resveratrol intake) decreased fasting blood glucose [-0.533 (-1.034 to -0.033); P=0.037] and triglyceride [-1.014 (-1.998 to -0.029); P=0.044] concentrations, and heart rate [-0.277 (-0.467 to -0.087); P=0.004]. Both resveratrol and wine intake, evaluated as TRMs, were associated with beneficial changes in blood lipid profiles, fasting blood glucose (only resveratrol) and heart rate, suggesting that resveratrol intake via wine consumption might help to decrease CV risk factors.

Topics: Aged; Biomarkers; Biotransformation; Blood Glucose; Cardiovascular Diseases; Chromatography, Liquid; Cross-Sectional Studies; Diet, Mediterranean; Female; Heart Rate; Humans; Linear Models; Lipoproteins, HDL; Male; Middle Aged; Multivariate Analysis; Prevalence; Resveratrol; Solid Phase Extraction; Spain; Stilbenes; Tandem Mass Spectrometry; Triglycerides; Wine

The search for complementary treatments in primary prevention of cardiovascular disease (CVD) is a high-priority challenge. Grape and wine polyphenol resveratrol confers CV benefits, in part by exerting anti-inflammatory effects. However, the evidence in human long-term clinical trials has yet to be established. We aimed to investigate the effects of a dietary resveratrol-rich grape supplement on the inflammatory and fibrinolytic status of subjects at high risk of CVD and treated according to current guidelines for primary prevention of CVD. Seventy-five patients undergoing primary prevention of CVD participated in this triple-blinded, randomized, parallel, dose-response, placebo-controlled, 1-year follow-up trial. Patients, allocated in 3 groups, consumed placebo (maltodextrin), a resveratrol-rich grape supplement (resveratrol 8 mg), or a conventional grape supplement lacking resveratrol, for the first 6 months and a double dose for the next 6 months. In contrast to placebo and conventional grape supplement, the resveratrol-rich grape supplement significantly decreased high-sensitivity C-reactive protein (-26%, p = 0.03), tumor necrosis factor-α (-19.8%, p = 0.01), plasminogen activator inhibitor type 1 (-16.8%, p = 0.03), and interleukin-6/interleukin-10 ratio (-24%, p = 0.04) and increased anti-inflammatory interleukin-10 (19.8%, p = 0.00). Adiponectin (6.5%, p = 0.07) and soluble intercellular adhesion molecule-1 (-5.7%, p = 0.06) tended to increase and decrease, respectively. No adverse effects were observed in any patient. In conclusion, 1-year consumption of a resveratrol-rich grape supplement improved the inflammatory and fibrinolytic status in patients who were on statins for primary prevention of CVD and at high CVD risk (i.e., with diabetes or hypercholesterolemia plus ≥1 other CV risk factor). Our results show for the first time that a dietary intervention with grape resveratrol could complement the gold standard therapy in the primary prevention of CVD.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cardiovascular Diseases; Dietary Supplements; Double-Blind Method; Female; Fibrinolysis; Fruit; Humans; Inflammation; Male; Middle Aged; Phytotherapy; Plant Extracts; Resveratrol; Stilbenes; Time Factors; Vitis

The cardioprotective role of resveratrol as part of the human diet is not yet clear. Our aim was to investigate the effect of a grape supplement containing 8 mg resveratrol in oxidized LDL (LDLox), apolipoprotein-B (ApoB), and serum lipids on statin-treated patients in primary cardiovascular disease prevention (PCP).. A triple-blind, randomized, placebo-controlled trial was conducted. Seventy-five patients (three parallel arms) consumed one capsule (350 mg) daily for 6 months containing resveratrol-enriched grape extract (GE-RES, Stilvid®), grape extract (GE, similar polyphenolic content but no resveratrol), or placebo (maltodextrin). After 6 months, no changes were observed in the placebo group and only LDL cholesterol (LDLc) decreased by 2.9% (p = 0.013) in the GE group. In contrast, LDLc (-4.5%, p = 0.04), ApoB (-9.8%, p = 0.014), LDLox (-20%, p = 0.001), and LDLox/ApoB (-12.5%, p = 0.000) decreased in the Stilvid® group, whereas the ratio non-HDLc (total atherogenic cholesterol load)/ApoB increased (8.5%, p = 0.046). No changes were observed in hepatic, thyroid, and renal function. No adverse effects were observed in any of the patients.. This GE-RES reduced atherogenic markers and might exert additional cardioprotection beyond the gold-standard medication in patients from PCP. The presence of resveratrol in the GE was necessary to achieve these effects.

Topics: Aged; Apolipoproteins B; Cardiovascular Diseases; Dietary Supplements; Female; Follow-Up Studies; Humans; Kidney; Lipids; Lipoproteins, LDL; Liver; Male; Middle Aged; Plant Extracts; Resveratrol; Stilbenes; Thyroid Function Tests; Vitis

Flow-mediated dilatation of the brachial artery (FMD) is a biomarker of endothelial function and cardiovascular health. Impaired FMD is associated with several cardiovascular risk factors including hypertension and obesity. Various food ingredients such as polyphenols have been shown to improve FMD. We investigated whether consuming resveratrol, a polyphenol found in red wine, can enhance FMD acutely and whether there is a dose-response relationship for this effect.. 19 overweight/obese (BMI 25-35 kg m(-2)) men or post-menopausal women with untreated borderline hypertension (systolic BP: 130-160 mmHg or diastolic BP: 85-100 mmHg) consumed three doses of resveratrol (resVida™ 30, 90 and 270 mg) and a placebo at weekly intervals in a double-blind, randomized crossover comparison. One hour after consumption of the supplement, plasma resveratrol and FMD were measured. Data were analyzed by linear regression versus log(10) dose of resveratrol. 14 men and 5 women (age 55 ± 2 years, BMI 28.7 ± 0.5 kg m(-2), BP 141 ± 2/89 ± 1 mmHg) completed this study. There was a significant dose effect of resveratrol on plasma resveratrol concentration (P < 0.001) and on FMD (P < 0.01), which increased from 4.1 ± 0.8% (placebo) to 7.7 ± 1.5% after 270 mg resveratrol. FMD was also linearly related to log(10) plasma resveratrol concentration (P < 0.01).. Acute resveratrol consumption increased plasma resveratrol concentrations and FMD in a dose-related manner. This effect may contribute to the purported cardiovascular health benefits of grapes and red wine.

Topics: Brachial Artery; Cardiovascular Diseases; Cross-Over Studies; Dietary Supplements; Dose-Response Relationship, Drug; Double-Blind Method; Endothelium, Vascular; Female; Humans; Hypertension; Male; Middle Aged; Obesity; Overweight; Placebos; Resveratrol; Risk Factors; Stilbenes; Vasodilation

The previous evidence shows that there is an association between total dietary polyphenols intake (DPI) and its subclasses and lower risk of metabolic Syndrome (MetS). This cross-sectional study aims to evaluate associations between DPI and cardiometabolic factors in Iranian women.. A total of 404 Iranian women were included in this study. Dietary intakes and polyphenols intakes were measured using a validated semi-quantitative food frequency questionnaire (FFQ) and the Phenol-Explorer database, respectively. Biochemical variables and blood pressure were evaluated using Pars Azmoon kits and mercury sphygmomanometer.. The mean intake of total polyphenol was 2533.96 ± 1223.67 g. While there were significant negative associations between stilbenes and lignans intake and body mass index (BMI) (P-value = 0.04; P-value = 0.02, respectively), beverages containing phenolic acids and hip circumference (HC) (P-value = 0.02), total polyphenols intake and weight to hip ratio (WHR) (P-value = 0.04). Also there was significant negative associations between stilbenes intake and cholesterol (CHOL) level (P-value = 0.03), other polyphenols intake and triglyceride (TG) ((P-value = 0.01), lignan intake and homeostasis model assessment insulin resistance (HOMA-IR) (P-value = 0.03).. These findings demonstrated that dietary polyphenols were associated with cardiometabolic factors in Iranian women. Prospective and interventional studies in both genders, different populations and ethnicities need to be conducted to further the knowledge about examine associations between consumption of polyphenols and metabolic component.

Topics: Cardiovascular Diseases; Cross-Sectional Studies; Diet; Eating; Female; Humans; Iran; Male; Obesity; Overweight; Polyphenols; Prospective Studies; Stilbenes

Postprandial hyperglycemia in diabetic and nondiabetic subjects is associated with endothelial dysfunction. Evidence shows that high glucose generates oxidative stress and a pro-inflammatory state promoting the development of cardiovascular diseases. trans-Resveratrol (t-RV) has been shown to reduce cardiovascular risk. To determine whether t-RV acts as a protector against acute high glucose (AHG)-induced damage, two in vitro models, rat aortic rings (RAR) and human umbilical vein endothelial cells (HUVEC) were used. RAR pretreated with AHG (25 mM D-glucose) for 3 h dramatically decreased the endothelium-dependent relaxation (EDR) induced by acetylcholine in phenylephrine (PE)-precontracted vessels. However, coincubation with t-RV significantly mitigated the damage induced by AHG on EDR. Pretreatment with AHG did not affect the vasodilation induced by sodium nitroprusside. HUVEC treated with t-RV decreased cytotoxicity and reduced radical oxygen species production induced by AHG. Taken together, these results suggest that t-RV can mitigate the AHG-induced EDR damage through a mechanism involving ROS scavenging and probably an increase in the bioavailability of NO.

Topics: Acetylcholine; Animals; Aorta; Blood Glucose; Cardiovascular Diseases; Endothelium, Vascular; Human Umbilical Vein Endothelial Cells; Humans; Hyperglycemia; Male; Nitric Oxide; Nitroprusside; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Resveratrol; Stilbenes; Vasodilation

Topics: AMP-Activated Protein Kinases; Animals; Body Weight; Cardiovascular Diseases; Eating; Female; Fetal Growth Retardation; Heart; Male; Myocardium; Oxidative Stress; Phosphorylation; Rats; Rats, Sprague-Dawley; Resveratrol; Stilbenes

Prenatal hypoxia, a common outcome of pregnancy complications, predisposes offspring to the development of metabolic and cardiovascular disorders in later life. We have previously observed that resveratrol improved cardiovascular and metabolic health in adult male rat offspring exposed to prenatal hypoxia and a postnatal high-fat (HF) diet; however, the effects of resveratrol in female rat offspring are not known. Our aim was to identify the mechanism(s) by which resveratrol may prevent metabolic and cardiac dysfunction in both male and female rat offspring exposed to prenatal hypoxia and a postnatal HF diet. Offspring that experienced normoxia or hypoxia in utero were fed a HF diet or a HF diet supplemented with resveratrol for 9 weeks following weaning. Body composition, metabolic function, in vivo cardiac function and ex vivo cardiac susceptibility to ischaemia-reperfusion (I/R) injury were assessed at 12 weeks of age. Prenatal hypoxia impaired metabolic function in male, but not female, rat offspring fed a HF diet and this was improved by resveratrol supplementation. Prenatal hypoxia also led to reduced recovery from cardiac I/R injury in male, and to a lesser extent in female, rat offspring fed a HF diet. Indices of cardiac oxidative stress after I/R were enhanced in both male and female rat offspring exposed to prenatal hypoxia. Resveratrol improved cardiac recovery from I/R injury and attenuated superoxide levels in both male and female rat offspring. In conclusion, prenatal hypoxia impaired metabolic and cardiac function in a sex-specific manner. Resveratrol supplementation may improve metabolic and cardiovascular health in adult male and female rat offspring exposed to prenatal hypoxia.

Topics: Animals; Cardiotonic Agents; Cardiovascular Diseases; Diet, High-Fat; Female; Fetal Hypoxia; Heart; Male; Myocardial Contraction; Myocardium; Pregnancy; Rats; Rats, Sprague-Dawley; Resveratrol; Stilbenes; Superoxides; Ventricular Function

Diabetes-induced CVD is the most significant complication of prolonged hyperglycaemia. The aim of this study was to determine whether resveratrol, a polyphenol antioxidant compound, when administered at a dose that can be reasonably obtained through supplementation could prevent the development of cardiovascular complications in older, obese, diabetic rats. Diabetes was induced in 6-month old, obese, male Wistar rats via a single intravenous dose of streptozotocin (65 mg/kg). Randomly selected animals were administered resveratrol (2 mg/kg) via oral gavage daily for 8 weeks. Body weights, blood glucose levels, food intake and water consumption were monitored, and assessments of vascular reactivity, tactile allodynia and left ventricular function were performed. Resveratrol therapy significantly improved tactile allodynia and vascular contractile functionality in diabetic rats (P<0·05). There were no significant changes in standardised vasorelaxation responses, plasma glucose concentrations, water consumption, body weight, left ventricular hypertrophy, kidney hypertrophy, heart rate or left ventricular compliance with resveratrol administration. Resveratrol-mediated improvements in vascular and nerve function in old, obese, diabetic rats were associated with its reported antioxidant effects. Resveratrol did not improve cardiac function nor mitigate the classic clinical symptoms of diabetes mellitus (i.e. hyperglycaemia, polydypsia and a failure to thrive). This suggests that supplementation with resveratrol at a dose achievable with commercially available supplements would not produce significant cardioprotective effects in people with diabetes mellitus.

Topics: Analgesics; Animals; Antioxidants; Cardiovascular Diseases; Diabetes Mellitus, Experimental; Endothelium, Vascular; Hyperalgesia; Male; Muscle Contraction; Nervous System; Obesity; Plant Extracts; Polyphenols; Random Allocation; Rats, Wistar; Resveratrol; Stilbenes

This study investigated possible mechanisms for cardioprotective effects of lipoic acid (LA), quercetin (Q) and resveratrol (R) on oxidative stress related to thyroid hormone alterations in long-term obesity. Female C57BL/6 mice were fed on high-fat diet (HFD), HFD+LA, HFD+R, HFD+Q and normal diet for 26weeks. Body weight, blood pressure, thyroid hormones, oxidative stress markers, angiotensin converting enzyme (ACE), nitric oxide synthase (NOS) and ion pump activities were measured, and expression of cardiac genes was analyzed by real-time polymerase chain reaction. HFD induced marked increase (P<.05) in body weight, blood pressure and oxidative stress, while plasma triidothyronine levels reduced. ACE activity increased (P<.05) in HFD mice (0.69±0.225U/mg protein) compared with controls (0.28±0.114U/mg protein), HFD+LA (0.231±0.02U/mg protein) and HFD+Q (0.182±0.096U/mg protein) at 26weeks. Moreover, Na(+)/K(+)-ATPase and Ca(2+)-ATPase activities increased in HFD mice whereas NOS reduced. A 1.5-fold increase in TRα1 and reduction in expression of the deiodinase iodothyronine DIO1, threonine protein kinase and NOS3 as well as up-regulation of AT1α, ACE, ATP1B1, GSK3β and Cja1 genes also occurred in HFD mice. Conversely, LA, Q and R inhibited weight gain; reduced TRα1 expression as well as increased DIO1; reduced ACE activity and AT1α, ATP1B1 and Cja1 gene expression as well as inhibited GSK3β; increased total antioxidant capacity, GSH and catalase activity; and reduced blood pressure. In conclusion, LA, resveratrol and quercetin supplementation reduces obesity thereby restoring plasma thyroid hormone levels and attenuating oxidative stress in the heart and thus may have therapeutic potential in heart diseases.

Topics: Animals; Anti-Obesity Agents; Antihypertensive Agents; Antioxidants; Biomarkers; Cardiotonic Agents; Cardiovascular Diseases; Diet, High-Fat; Female; Gene Expression Regulation; Heart Ventricles; Hypertension; Hypothyroidism; Mice, Inbred C57BL; Obesity; Oxidative Stress; Quercetin; Random Allocation; Resveratrol; Stilbenes; Thioctic Acid; Thyroid Hormones; Weight Gain

Arterial stiffness, a major cardiovascular risk factor, develops within 2 months in mice fed a high-fat, high-sucrose (HFHS) diet, serving as a model of human metabolic syndrome, and it is associated with activation of proinflammatory and oxidant pathways in vascular smooth muscle (VSM) cells. Sirtuin-1 (SirT1) is an NAD(+)-dependent deacetylase regulated by the cellular metabolic status. Our goal was to study the effects of VSM SirT1 on arterial stiffness in the context of diet-induced metabolic syndrome. Overnight fasting acutely decreased arterial stiffness, measured in vivo by pulse wave velocity, in mice fed HFHS for 2 or 8 months, but not in mice lacking SirT1 in VSM (SMKO). Similarly, VSM-specific genetic SirT1 overexpression (SMTG) prevented pulse wave velocity increases induced by HFHS feeding, during 8 months. Administration of resveratrol or S17834, 2 polyphenolic compounds known to activate SirT1, prevented HFHS-induced arterial stiffness and were mimicked by global SirT1 overexpression (SirT1 bacterial artificial chromosome overexpressor), without evident metabolic improvements. In addition, HFHS-induced pulse wave velocity increases were reversed by 1-week treatment with a specific, small molecule SirT1 activator (SRT1720). These beneficial effects of pharmacological or genetic SirT1 activation, against HFHS-induced arterial stiffness, were associated with a decrease in nuclear factor kappa light chain enhancer of activated B cells (NFκB) activation and vascular cell adhesion molecule (VCAM-1) and p47phox protein expressions, in aorta and VSM cells. In conclusion, VSM SirT1 activation decreases arterial stiffness in the setting of obesity by stimulating anti-inflammatory and antioxidant pathways in the aorta. SirT1 activators may represent a novel therapeutic approach to prevent arterial stiffness and associated cardiovascular complications in overweight/obese individuals with metabolic syndrome.

Topics: Animals; Blotting, Western; Cardiovascular Diseases; Diet, High-Fat; Disease Models, Animal; Glucose Tolerance Test; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Muscle, Smooth, Vascular; Obesity; Pulse Wave Analysis; Random Allocation; Real-Time Polymerase Chain Reaction; Resveratrol; Sirtuin 1; Stilbenes; Vascular Cell Adhesion Molecule-1; Vascular Stiffness

The effects of chronic administration of piceatannol-enriched (9.5% w/w) passion fruit seed extract (PFSE) on the cardiovascular damage induced in a high-fat (HF) diet-fed model of Fischer 344 rats were evaluated. Rats were fed the control, HF, or HF diets containing PFSE (0.5% w/w) for 16 weeks, and the effects of the various diets on the tissue weight, serum lipid profile, hepatic fibrosis, hepatic ductular reaction, cardiac function and aortic ring reactivity were examined. HF diet-fed rats developed signs of cardiovascular disease with abnormal serum profiles compared to control diet-fed rats. PFSE supplementation improved the liver hypertrophy and hepatic histology of the HF diet-fed rats. In addition, the triglyceride and cholesterol levels, platelet aggregation, cardiac function, and acetylcholine-mediated relaxation of the aortic ring were improved. These results suggest that the chronic intake of PFSE containing piceatannol prevents HF diet-induced cardiovascular disease in rats.

Topics: Animals; Aorta; Cardiovascular Diseases; Diet, High-Fat; Dietary Supplements; Heart Ventricles; Hypolipidemic Agents; Lipotropic Agents; Liver; Male; Non-alcoholic Fatty Liver Disease; Organ Size; Passiflora; Plant Extracts; Platelet Aggregation Inhibitors; Random Allocation; Rats, Inbred F344; Seeds; Stilbenes; Vascular Resistance

Cardiovascular disease (CVD) is the leading cause of death in Europe. One of the candidate molecule affecting epigenetic mechanisms of CVD is the SIRT1, a subclass of sirtuins, is located on the long arm of chromosome 10 (10q21.3). Particularly, the relation between 2827 A>G polymorphism of the SIRT1 positioned on exon 2, leading to conversion of histidine to arginine, and the formation of CVD is not known yet. One of the activator of SIRT1, resveratrol, is also known as a cardioprotective molecule. On the other hand, the parameters including exercise, occupation and age affect CVD. The aim of the present study was to investigate the effect of the rs144124002 (2827 A>G) single nucleotide polymorphisms (SNP) of SIRT1 and exercise-occupation-age parameters on CVD.. SNP of SIRT1 were analyzed using DNA isolation, the polymerase chain reaction (PCR) and restriction fragment length polymorphism. To do so, large cohorts of CVD patients (n=293) and healthy controls (n=117) who directed Cardiology Department of Bezmialem Vakıf University, Bezmialem Vakıf University Hospital were used.. In this study, when we assessed CVD and control groups about 2827 A>G polymorphism, all individuals were determined as homozygous genotype. We found a positive effect between the modifications of resveratrol, exercise, age and occupation and CVD (OR=0.17; CI 95%, 0.1-0.2; p ≤ 0.001).. This is the first study demonstrating the correlation between the SIRT1 rs144124002 polymorphism and CVD in Turkish population.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Cardiovascular Diseases; Case-Control Studies; DNA; Exercise; Female; Gene-Environment Interaction; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Occupations; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Resveratrol; Sirtuin 1; Stilbenes; Turkey

Topics: Antioxidants; Cacao; Cardiovascular Diseases; Cognition; Flavonoids; Functional Food; Humans; Resveratrol; Stilbenes

Topics: Animals; Cardiotonic Agents; Cardiovascular Diseases; Humans; Stilbenes

The cardioprotective effects of resveratrol are well established in animal models of metabolic disease but are yet to be investigated in a combined model of hypertension and diabetes. This study investigated the ability of resveratrol's antioxidant and anti-inflammatory effects to prevent cardiovascular complications in the spontaneously hypertensive streptozotocin-induced diabetic rat. Diabetes was induced in eight-week-old male spontaneously hypertensive rats via a single intravenous injection of streptozotocin. Following this, resveratrol was administered orally for an eight-week period until the animals were sixteen weeks of age. Upon completion of the treatment regime assessments of oxidative stress, lipid peroxidation, inflammation, and cardiovascular function were made. Resveratrol administration to hypertensive-diabetic animals did not impact upon blood glucose or haemodynamics but significantly reduced oxidative stress, lipid peroxidation, and inflammatory cytokines. Reductions in systemic levels of oxidative stress and inflammation conferred improvements in vascular reactivity and left ventricular pump function and electrophysiology. This study demonstrates that resveratrol administration to hypertensive diabetic animals can elicit cardioprotective properties via antioxidant and anti-inflammatory effects. The observed preservation of cardiovascular function was independent of changes in blood glucose concentration and haemodynamics, suggesting that oxidative stress and inflammation are key components within the pathological cascade associated with hypertension and diabetes.

Topics: Acetylcholine; Animals; Blood Vessels; Body Weight; Cardiovascular Diseases; Diabetes Mellitus, Experimental; Drinking; In Vitro Techniques; Inflammation; Lipid Peroxidation; Male; Microelectrodes; Myocardial Contraction; Nitric Oxide; Nitroprusside; Norepinephrine; Oxidative Stress; Rats, Inbred SHR; Resveratrol; Stilbenes; Streptozocin; Ventricular Function

Advanced glycation end products (AGEs) by nonenzymatic glycation reactions are extremely accumulated in the diabetic vascular cells, neurons, and glia, and are confirmed to play important role in the pathogenesis of diabetes mellitus -induced cardiovascular complications. Sirt 1, known as mammalian sirtuin, has been recognized to regulate insulin secretion and protect cells against oxidative stress, which is promoted by the accumulated AGEs in cardiovascular cells. In the present study, we treated human endothelial Eahy926 cells with AGEs, and determined the apoptosis induction, caspase activation, the Sirt 1 activity, the expression and acetylation of p53. Then we manipulated Sirt 1 activity with a Sirt 1 activator, Resveratrol (RSV), and a Sirt 1 inhibitor, sirtinol, in the AGE-BSA-treated Eahy926 cells, and then re-evaluated the apoptosis induction, caspase activation, the expression and acetylation of p53. Results demonstrated that AGEs induced apoptosis in the human endothelial Eahy926 cells, by promoting the cytochrome c release, activation of caspase 9/3. Also, the AGE-BSA treatment promoted the total p53 level and acetylated (Ac) p53, but reduced the Sirt 1 level and activity. On the other hand, the Sirt 1 inhibitor/activator not only deteriorated/ameliorated the promotion to p53 level and Ac p53, but also aggravated/inhibited the AGE-induced apoptosis and the promotion to apoptosis-associated signaling molecules. In conclusion, the present study confirmed the apoptosis promotion by AGEs in endothelial Eahy926 cells, by regulating the Sirt 1 activity and p53 signaling, it also implies the protective role of Sirt 1 activator against the AGE-induced apoptosis.

Topics: Acetylation; Apoptosis; Benzamides; Cardiovascular Diseases; Caspases; Cells, Cultured; Cytochromes c; Diabetes Mellitus; Endothelial Cells; Glycation End Products, Advanced; Humans; Insulin; Insulin Secretion; Naphthols; Oxidative Stress; Resveratrol; Signal Transduction; Sirtuin 1; Stilbenes; Tumor Suppressor Protein p53

Topics: Animals; Cardiotonic Agents; Cardiovascular Diseases; Humans; Stilbenes

Topics: Antioxidants; Cardiovascular Diseases; Dietary Supplements; Humans; Longevity; Resveratrol; Stilbenes; Wine

Atherogenic or high fat diets were known to induce cardiovascular diseases, and several active compounds were tested to protect/prevent the risk of cardiovascular diseases. We aimed to investigate the cardio protective effect of resveratrol against atherogenic diet fed rats. Male Wistar rats were administered atherogenic diet for 30 days and further continued for 15 days with or with resveratrol in the diet. The serum lipid profile, antioxidant enzyme activity, lipid peroxidation, lipid metabolic proteins and cardiac tissue markers were examined. The histopathology of myocardium and aorta were also examined. The abnormal serum lipid profile found in atherogenic rats was reversed by the administration of resveratrol. Similarly, the enzymatic (catalase, superoxide dismutase, glutathione-peroxidase), non-enzymatic (reduced-glutathione, Vitamin C, E) antioxidants were improved by the resveratrol fed against atherogenic diet. Interestingly, resveratrol activated the lipid metabolic proteins (SIRT1, eNOS and AMPKa), suggesting its protective effect on lipid metabolism. Further analysis on tissue damage revealed that resveratrol had significantly protected the tissue damage and maintains the morphology of cardiac tissue. Altogether, our results suggest that resveratrol played a significant role in the prevention of cardiovascular system against the high fat diet. Emphasising the anti-atherogenic property of resveratrol, we propose resveratrol as a potential compound to be consumed for the healthy life-style.

Topics: Adenylate Kinase; Animals; Antioxidants; Aorta; Cardiovascular Diseases; Catalase; Diet, Atherogenic; Glutathione Peroxidase; Heart; Lipid Metabolism; Lipid Peroxidation; Lipids; Male; Myocardium; Oxidative Stress; Rats; Rats, Wistar; Resveratrol; Sirtuin 1; Stilbenes; Superoxide Dismutase

The scientific evidence for the association of daily flavonoid and stilbene intakes with cardiovascular risk factors in Chinese adults has not been reported previously.. The aim of the study was to assess daily flavonoid and stilbene intakes and evaluate these compounds' association with cardiovascular risk factors such as serum lipids and carotid intima-media thickness in Chinese adults.. A total of 1,393 subjects participated in this cross-sectional study from July 2008 to January 2010 in China. Dietary flavonoid and stilbene intakes as well as overall dietary intakes from foods and beverages were assessed with a quantitative food frequency questionnaire. Anthropometric measurements and cardiovascular risk factors including serum lipids, uric acid, and carotid intima-media thickness were examined. The relationship between flavonoids and stilbene intakes and these cardiovascular risk factors was examined using either partial correlation coefficients or analysis of covariance.. The richest sources of flavonoids and stilbenes were the fruit group including apple, plum, pear, and peach, followed by the vegetable group containing lotus root and taro. The daily intake of total flavonoids, anthocyanidins, flavonols, flavones, isoflavones, and stilbene were 165.6 mg/day, 27.6 mg/day, 123.7 mg/day, 10.7 mg/day, 3.7 mg/day, and 0.3 mg/day, respectively. Higher daily consumption of anthocyanidins was associated with elevated serum high-density lipoprotein cholesterol (HDL-C) concentrations (P trend=0.001), and higher total flavonoid and flavonol intakes were associated with lower serum triglycerides (TG) concentrations (P trend=0.020 and P trend=0.035, respectively) and TG/HDL-C ratios (P trend=0.040 and P trend=0.045, respectively) in female subjects. These significant relationships were not found in male subjects.. The daily intakes of flavonoid and stilbene were estimated in the present study, and higher dietary flavonoid intake was associated with improving lipid profile in Chinese women. The results indicate that dietary flavonoids may have beneficial effect on preventing cardiovascular diseases.

Topics: Adult; Aged; Cardiovascular Diseases; Carotid Intima-Media Thickness; Cross-Sectional Studies; Diet; Female; Flavonoids; Fruit; Humans; Lipid Metabolism; Lipids; Male; Middle Aged; Nuts; Risk Factors; Sex Factors; Stilbenes; Vegetables

Many organs suffer from ischaemic injuries that reduce their ability to generate sufficient energy, which is required for functional maintenance and repair. Erythropoietin (EPO) ameliorates ischaemic injuries by pleiotropic effects. The aim of this study was to investigate the effect and mechanism of a small molecule EH-201, and found it as a potent EPO inducer and its effect in non-haematopoietic cells for therapeutic potential in ischemic disorders.. Mice kidney slices, primary hepatocytes, primary cardiomyocytes and C2C12 myoblasts were treated with EH-201. The effects of this treatment on EPO, Hb expression and mitochondrial biogenesis were analysed. In vivo, doxorubicin-induced cardiomyopathic mice were treated with EH-201. The mice were subjected to an endurance test, electrocardiography and echocardiography, and a histological examination of the isolated hearts was performed. EH-201 was also administered to cisplatin-induced nephropathic mice.. In non-haematopoietic cells, EH-201 was potent at inducing EPO. EH-201 also stimulated mitochondrial biogenesis and enhanced the expression of Hb by a mechanism dependent on EPO-mediated signalling. In mechanistic studies, using EPO and EPO receptor-neutralizing antibodies, we confirmed that EH-201 enhances EPO-EPOR autocrine activity. EH-201 robustly increased the endurance performance activity of healthy and cardiomyopathic mice during hypoxic stress, enhanced myocardial mitochondrial biogenesis and Hb expression, and also improved cardiac function. EH-201 ameliorated anaemia and renal dysfunction in nephropathic mice.. The enhancement and recovery of cellular functions through the stimulation of mitochondrial activity and Hb production in non-haematopoietic cells by an inducer of endogenous EPO has potential as a therapeutic strategy for ischaemic diseases.

Topics: Animals; Cardiovascular Diseases; Cell Line; Cells, Cultured; Cisplatin; Doxorubicin; Erythropoietin; Glucosides; HEK293 Cells; Hemoglobins; Hepatocytes; Humans; Kidney; Male; Mice; Mice, Inbred C57BL; Mitochondria; Myocytes, Cardiac; Receptors, Erythropoietin; Stilbenes

Epidemiological and clinical trials reveal compelling evidence for the ability of dietary flavonoids to lower cardiovascular disease risk. The mechanisms of action of these polyphenolic compounds are diverse, and of particular interest is their ability to function as protein and lipid kinase inhibitors. We have previously described structure-activity studies that reinforce the possibility for using flavonoid structures as templates for drug design. In the present study, we aim to begin constructing rational screening strategies for exploiting these compounds as templates for the design of clinically relevant, antiplatelet agents. We used the platelet as a model system to dissect the structural influence of flavonoids, stilbenes, anthocyanidins, and phenolic acids on inhibition of cell signaling and function. Functional groups identified as relevant for potent inhibition of platelet function included at least 2 benzene rings, a hydroxylated B ring, a planar C ring, a C ring ketone group, and a C-2 positioned B ring. Hydroxylation of the B ring with either a catechol group or a single C-4' hydroxyl may be required for efficient inhibition of collagen-stimulated tyrosine phosphorylated proteins of 125 to 130 kDa, but may not be necessary for that of phosphotyrosine proteins at approximately 29 kDa. The removal of the C ring C-3 hydroxyl together with a hydroxylated B ring (apigenin) may confer selectivity for 37 to 38 kDa phosphotyrosine proteins. We conclude that this study may form the basis for construction of maps of flavonoid inhibitory activity on kinase targets that may allow a multitargeted therapeutic approach with analogue counterparts and parent compounds.

Topics: Anthocyanins; Blood Platelets; Cardiovascular Diseases; Drug Design; Flavonoids; Humans; Hydroxybenzoates; Platelet Aggregation Inhibitors; Polyphenols; Signal Transduction; Stilbenes; Structure-Activity Relationship

In the present study, we examined the effect of repeated and long-term treatment with resveratrol on NO production in endothelial cells as a model of routine wine consumption. Repeated treatment with resveratrol for 5 d resulted in an increase in endothelial NO synthase (eNOS) protein content and NO production in human umbilical vein endothelial cell (HUVEC) in a concentration-dependent manner. A significant increase in functional eNOS protein content was observed with resveratrol, even at 50 nm. In contrast, eNOS phosphorylation was not stimulated and inducible NO synthase (iNOS) was not detected after resveratrol treatment. Both eNOS protein and mRNA expression were promoted by 50 nm-resveratrol in a time-dependent manner. Increased eNOS mRNA expression in response to resveratrol was not decreased by an oestrogen receptor (ER) antagonist ICI182780, a PPARα inhibitor MK886 or a sirtuin inhibitor Salermide. However, a combination of ICI182780 and MK886 significantly inhibited resveratrol-induced eNOS mRNA expression. Salermide had no effect even in the presence of ICI182780 or MK886. These results demonstrate that resveratrol within the physiological range increases eNOS mRNA and protein expression through ER and PPARα activation, thereby promoting NO production in endothelial cells. eNOS induction might result from the accumulative effect of nanomolar concentrations of resveratrol. The present study results can account in part for the observation that cardiovascular benefits of red wine are experienced with routine consumption, but not with acute consumption.

Topics: Antioxidants; Cardiovascular Diseases; Cells, Cultured; Endothelium, Vascular; Enzyme Induction; Enzyme Inhibitors; Estrogen Antagonists; Human Umbilical Vein Endothelial Cells; Humans; Nitric Oxide; Nitric Oxide Synthase Type III; Osmolar Concentration; Phosphorylation; PPAR alpha; Protein Processing, Post-Translational; Resveratrol; RNA, Messenger; Stilbenes; Time Factors; Up-Regulation; Wine

Aronia melanocarpa fruits (Rosaceae) are one of the richest plant sources of phenolic substances, and it has been shown to have various biological activities. Berries of A. melanocarpa (chokeberry) have been supposed to be beneficial for the prevention of cardiovascular events. In this study the influence of aronia extract on the clot formation (using human plasma and purified fibrinogen) and the fibrin lysis during the model of hyperhomocysteinemia was investigated.. Hyperhomocysteinemia was induced using a reduced form of Hcys (at final dose of 0.1mM) and the most reactive form of Hcys - its cyclic thioester, homocysteine thiolactone (HTL, 1 μM). The aim of our study in vitro was also to investigate the modifications of human plasma total proteins and the oxidative stress (by measuring the total antioxidant level - TAS) in plasma after incubation with Hcys, HTL and/or aronia extract. The biological properties of aronia extract were compared with the action of a well characterized antioxidative commercial polyphenol - resveratrol (3,4',5- trihydroxystilbene).. The HTL, like its precursor, Hcys stimulated polymerization of fibrinogen. The results also demonstrated that Hcys (0.1mM) and HLT at lower doses than Hcys (1 μM) reduced the fibrin lysis in human plasma. Moreover, Hcys and HTL change the level of thiol and amino groups in plasma total proteins and induce the oxidative stress in plasma. Our results indicate that aronia extract reduced the biotoxicity action of Hcys and HTL on hemostatic properties of fibrinogen or plasma, suggesting its possible protective properties in hyperhomocysteinemia - induced cardiovascular diseases. Moreover, our results showed that the extract from berries of A. melanocarpa due to antioxidant action, significantly reduced the oxidative stress (measured by TAS) in plasma during the model of hyperhomocysteinemia.. In the comparative studies, the extract from berries of A. melanocarpa and reseveratrol had similar protective properties. It gives hopes for development of diet supplements, which may be preventing thrombosis in pathological states where plasma procoagulant activity and oxidative stress are observed e.g. in hyperhomocysteinemia.

Topics: Adult; Anticoagulants; Antioxidants; Blood Coagulation; Cardiovascular Diseases; Coagulants; Dietary Supplements; Fibrinogen; Fruit; Homocysteine; Humans; Hyperhomocysteinemia; Models, Biological; Oxidative Stress; Photinia; Plant Extracts; Poland; Polymerization; Resveratrol; Stilbenes

Redox state unbalance and the activation of the arachidonic acid (AA) cascade, contribute to the pathogenesis of cardiovascular disease (CVD) and cancer. Inflammatory cells that infiltrate the atheroma plaque or tumor are a major source of reactive oxygen species and eicosanoids. The human antioxidant defense network is complex and interlocking and there is controversy surrounding the beneficial effects of diet-derived antioxidants in vivo. However, epidemiological studies indicate that populations that consume high levels of plant-derived foods containing phenolic compounds have low rates of CVD and cancer. The molecular mechanisms for these effects are multi-faceted. They include the regulation of transcription factors and consequently the modulation of genes (cytokines, growth factors and adhesion molecules), and growth factor-receptor interactions and cell signaling cascades, which determine the expression of genes involved in cell cycle, cell survival and apoptosis, as well as adhesiveness/invasiveness and angiogenesis. The present paper also focuses on the effects of phenolic compounds on AA cascade enzymes (cyclooxygenases and lipoxygenases) and the subsequent synthesis of eicosanoids, which are involved in CVD and cancer. A better understanding of these processes could explain the beneficial effects of polyphenols on the most prevalent diseases in Western societies. This commentary shows that antioxidants under evaluation include structural modifications of low-molecular-mass polyphenols, which could lead to a valuable strategy for modulating the generation of inflammatory mediators involved in these chronic diseases.

Topics: Acetylation; Animals; Anthocyanins; Antioxidants; Arachidonic Acid; Biological Availability; Cardiovascular Diseases; Chemoprevention; Dietary Supplements; Flavones; Food; Histones; Humans; Neoplasms; Nitric Oxide; Oxidative Stress; Polyphenols; Prevalence; Signal Transduction; Stilbenes

Polyphenols (PPH) are a group of chemical substances found in plants, characterized by the presence of more than one phenol unit . The largest and best studied polyphenols are the flavonoids, which include several thousand compounds. PPH are the most abundant antioxidants in human diets. Their sheer mass in the diet exceeds that of the consumed vitamins. The Mediterranean diet is rich in PPH because it contains abundant vegetables, fruits, unrefined cereals, legumes, nuts, garlic, olive oil and red wine. Locations where the Mediterranean diet prevails are known for a reduced premature cardiovascular disease (CVD) mortality. However, this geographic distinction is not entirely unique. Low CVD mortality is also present in countries with high consumption if plant food and fish, as Scandinavia, Switzerland and Austria. Putative mechanisms of the metabolic effect of PPH are related to multiple biologic functions that may have beneficial effect in the prevention of some inflammation-mediated disorders, including CVD. Naturally occurring dietary PPH can directly scavenge free oxygen radicals, adhesion molecules, and growth factor receptor genes. Thus, these polyphenolic compounds have potential therapeutic value as antioxidant and anti-inflammatory agents in CVD. PPH reduce the generation of oxidized low density lipoproteins (LDL), induce nitric oxide (NO) production, inhibit platelet aggregation and downregulate expression of proinflammatory mediators (Fig. 6, Tab. 1, Ref. 33).

Topics: 4-Butyrolactone; Anti-Inflammatory Agents; Antioxidants; Cardiovascular Diseases; Curcumin; Diet, Mediterranean; Humans; Lignans; Plants; Polyphenols; Resveratrol; Stilbenes

Topics: Age of Onset; Aging; Animal Diseases; Animals; Biomedical Research; Caloric Restriction; Cardiovascular Diseases; Female; Gene Expression Profiling; Geriatrics; Humans; Longevity; Macaca mulatta; Male; Mice; Models, Animal; Neoplasms; Oligonucleotide Array Sequence Analysis; Reproducibility of Results; Resveratrol; Sirolimus; Sirtuins; Somatomedins; Stilbenes; TOR Serine-Threonine Kinases

The phytoalexin resveratrol (3,4',5-trihydroxy-trans-stilbene) may attenuate cardiovascular disease in man. This study has determined whether treatment with resveratrol (1 mg/kg/day orally) prevented cardiac fibrosis and the decreased cardiovascular function in the DOCA-salt hypertensive rat as a model of human hypertension. Uninephrectomised rats (UNX) administered DOCA (25mg every 4th day sc) and 1% NaCl in drinking water for 28 days developed cardiac and vascular remodelling. In these DOCA-salt rats, resveratrol decreased inflammatory cell infiltration, decreased cardiac fibrosis (left ventricular interstitial and perivascular collagen content) and improved cardiac and vascular function. Resveratrol attenuated other features of cardiovascular remodelling such as increases in systolic blood pressure, left ventricular wet weight, left ventricular wall thickness, diastolic stiffness constant, as well as decreased cardiac contractility and prolonged action potential duration characteristic of DOCA-salt rats. In summary, resveratrol, at a nutritionally relevant dose, prevents or attenuates the adverse changes in the cardiovascular system. We propose that the anti-inflammatory and anti-fibrotic effects of resveratrol are responsible, at least in part, for its amelioration in cardiovascular remodelling in DOCA-salt rats. These actions of resveratrol could play an important role in the protective effects on the human cardiovascular system reported for this constituent of red wine.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Blood Pressure; Cardiovascular Diseases; Cardiovascular Physiological Phenomena; Desoxycorticosterone; Fibrosis; Heart; Heart Ventricles; Humans; Hypertension; Male; Mineralocorticoids; Rats; Rats, Wistar; Resveratrol; Sodium Chloride, Dietary; Stilbenes; Ventricular Remodeling

Trans-resveratrol is a nutraceutical with known antioxidant, anti-inflammatory, cardioprotective, and anti-apoptotic properties. The aim of this study was to evaluate the effects of resveratrol on heart mitochondria. Resveratrol significantly decreased Fe(2+) + ascorbate oxidant system-induced lipid peroxide levels, preserved physiological levels of glutathione, and increased nitric oxide (NO) levels in mitochondria. Under calcium-mediated stress, there was a 2.7-fold increase in the NO levels, and a mild decoupling in the mitochondrial respiratory chain. These results provide a mechanism for and support the beneficial effects of resveratrol under pathological conditions induced by oxidative stress and calcium overload. In addition, these findings underscore the usefulness of resveratrol in the prevention of cardiovascular diseases.

Topics: Animals; Antioxidants; Ascorbic Acid; Calcium; Cardiovascular Diseases; Glutathione; Iron; Male; Mitochondria, Heart; Nitric Oxide; Oxidative Stress; Rats; Rats, Wistar; Resveratrol; Stilbenes

Topics: AMP-Activated Protein Kinases; Animals; Cardiovascular Diseases; Enzyme Inhibitors; Humans; Insulin Resistance; Obesity; Resveratrol; Sirtuin 1; Stilbenes

Epidemiological studies suggest that Mediterranean diets rich in resveratrol are associated with reduced risk of coronary artery disease. Resveratrol was also shown to confer vasoprotection in animal models of type 2 diabetes and aging. However, the mechanisms by which resveratrol exerts its antioxidative vasculoprotective effects are not completely understood. Using a nuclear factor-E(2)-related factor-2 (Nrf2)/antioxidant response element-driven luciferase reporter gene assay, we found that in cultured coronary arterial endothelial cells, resveratrol, in a dose-dependent manner, significantly increases transcriptional activity of Nrf2. Accordingly, resveratrol significantly upregulates the expression of the Nrf2 target genes NAD(P)H:quinone oxidoreductase 1, gamma-glutamylcysteine synthetase, and heme oxygenase-1. Resveratrol treatment also significantly attenuated high glucose (30 mM)-induced mitochondrial and cellular oxidative stress (assessed by flow cytometry using MitoSox and dihydroethidine staining). The aforementioned effects of resveratrol were significantly attenuated by the small interfering RNA downregulation of Nrf2 or the overexpression of Kelch-like erythroid cell-derived protein 1, which inactivates Nrf2. To test the effects of resveratrol in vivo, we used mice fed a high-fat diet (HFD), which exhibit increased vascular oxidative stress associated with an impaired endothelial function. In HFD-fed Nrf2(+/+) mice, resveratrol treatment attenuates oxidative stress (assessed by the Amplex red assay), improves acetylcholine-induced vasodilation, and inhibits apoptosis (assessed by measuring caspase-3 activity and DNA fragmentation) in branches of the femoral artery. In contrast, the aforementioned endothelial protective effects of resveratrol were diminished in HFD-fed Nrf2(-/-) mice. Taken together, our results indicate that resveratrol both in vitro and in vivo confers endothelial protective effects which are mediated by the activation of Nrf2.

Topics: Animals; Antioxidants; Apoptosis; Cardiovascular Diseases; Cells, Cultured; Coronary Vessels; Cytoprotection; Dietary Fats; Disease Models, Animal; Dose-Response Relationship, Drug; Endothelial Cells; Femoral Artery; Genes, Reporter; Glucose; Glutathione Synthase; Heme Oxygenase-1; Humans; Intracellular Signaling Peptides and Proteins; Kelch-Like ECH-Associated Protein 1; Male; Mice; Mice, Inbred ICR; Mice, Knockout; NAD(P)H Dehydrogenase (Quinone); NF-E2-Related Factor 2; Oxidative Stress; Response Elements; Resveratrol; RNA Interference; Stilbenes; Transcriptional Activation; Transfection; Vasodilation

Topics: Animals; Antioxidants; Apoptosis; Cardiovascular Diseases; Cytoprotection; Endothelial Cells; Humans; Mice; NF-E2-Related Factor 2; Oxidative Stress; Response Elements; Resveratrol; Stilbenes; Transcriptional Activation; Vasodilation

Topics: Adipocytes; Alcohol Drinking; Antioxidants; Cardiovascular Diseases; Humans; Metabolic Diseases; Platelet Aggregation Inhibitors; Resveratrol; Stilbenes; Wine

Angiotensin II (Ang-II) displays inflammatory activity and is implicated in several cardiovascular disorders. This study evaluates the effect of cis- and trans (t)-resveratrol (RESV) in two in vivo models of vascular inflammation and identifies the cardioprotective mechanisms that underlie them. In vivo, Ang-II-induced arteriolar leukocyte adhesion was inhibited by 71% by t-RESV (2.1 mg/kg, i.v.), but was not affected by cis-RESV. Because estrogens influence the rennin-angiotensin system, chronic treatment with t-RESV (15 mg/kg/day, orally) inhibited ovariectomy-induced arteriolar leukocyte adhesion by 81%, partly through a reduction of cell adhesion molecule (CAM) expression and circulating levels of cytokine-induced neutrophil chemoattractant, MCP-1, and MIP-1alpha. In an in vitro flow chamber system, t-RESV (1-10 microM) undermined the adhesion of human leukocytes under physiological flow to Ang-II-activated human endothelial cells. These effects were accompanied by reductions in monocyte and endothelial CAM expression, chemokine release, phosphorylation of p38 MAPK, and phosphorylation of the p65 subunit of NF-kappaB. Interestingly, t-RESV increased the expression of peroxisome proliferator-activated receptor-gamma in human endothelial and mononuclear cells. These results demonstrate for the first time that the in vivo anti-inflammatory activity of RESV is produced by its t-RESV, which possibly interferes with signaling pathways that cause the upregulation of CAMs and chemokine release. Upregulation of proliferator-activated receptor-gamma also appears to be involved in the cardioprotective effects of t-RESV. In this way, chronic administration of t-RESV may reduce the systemic inflammatory response associated with the activation of the rennin-angiotensin system, thereby decreasing the risk of further cardiovascular disease.

Topics: Angiogenesis Inhibitors; Angiotensin II; Animals; Cardiovascular Diseases; Cell Communication; Cells, Cultured; Disease Models, Animal; Endothelium, Vascular; Female; Humans; Inflammation Mediators; Male; NF-kappa B; Ovariectomy; PPAR gamma; Rats; Rats, Sprague-Dawley; Resveratrol; Stereoisomerism; Stilbenes; Up-Regulation

Topics: Animals; Antioxidants; Cardiovascular Diseases; Cardiovascular System; Health Knowledge, Attitudes, Practice; Humans; Resveratrol; Saccharomyces cerevisiae; Stilbenes

Topics: Antioxidants; Cardiovascular Diseases; Humans; Neurodegenerative Diseases; Resveratrol; Sirtuin 1; Sirtuins; Stilbenes; Wine

Topics: Antioxidants; Cardiovascular Diseases; Flavonoids; Humans; Phenols; Polyphenols; Resveratrol; Stilbenes; Wine

Resveratrol (3,4',5-trihydroxystilbene) is a phytochemical believed to be partly responsible for the cardioprotective effects of red wine due to its numerous biological activities. Here, we studied biochemical pathways underlying peroxynitrite-mediated apoptosis in endothelial cells and potential mechanisms responsible for resveratrol cytoprotective action. Peroxynitrite triggered endothelial cell apoptosis through caspases-8, -9 and -3 activation implying both mitochondrial and death receptor apoptotic pathways. Resveratrol was able to prevent peroxynitrite-induced caspases-3 and -9 activation, but not caspase-8 activation. Additionally, peroxynitrite increased intracellular levels of Bax without affecting those of Bcl-2, increasing consequently the Bax/Bcl-2 ratio. This ratio decreased when cells where pre-incubated with 10 and 50 muM resveratrol, mainly due to resveratrol ability per se to increase Bcl-2 intracellular levels without affecting Bax intracellular levels. These results propose an additional mechanism whereby resveratrol may exert its cardioprotective effects and suggest a key role for Bcl-2 in the resveratrol anti-apoptotic action, especially in disrupting peroxynitrite-triggered mitochondrial pathway.

Topics: Animals; Antioxidants; Apoptosis; Apoptosis Regulatory Proteins; bcl-2-Associated X Protein; Cardiovascular Diseases; Caspases; Cattle; Cells, Cultured; Cytoprotection; Endothelial Cells; Mitochondria; Oxidative Stress; Peroxynitrous Acid; Proto-Oncogene Proteins c-bcl-2; Receptors, Death Domain; Resveratrol; Signal Transduction; Stilbenes

There is increasing interest in the study of the antioxidant actions of plant phenolic compounds as evidence shows that consumption of plant products rich in these compounds contributes to protection from a number of ailments including cardiovascular diseases. In the present study, the antioxidant effects of selected phenolic compounds from dietary sources, namely barbaloin, 6-gingerol and rhapontin, were investigated.. Low-density lipoprotein (LDL), erythrocytes and erythrocyte membranes were subjected to several in vitro oxidative systems. The antioxidant effects of the phenolic compounds were assessed by their abilities in inhibiting hemolysis and lipid peroxidation of LDL and erythrocyte membranes, and in protecting ATPase activities and protein sulfhydryl groups of erythrocyte membranes.. 6-Gingerol and rhapontin were found to exhibit strong inhibition against lipid peroxidation in LDL induced by 2,2'-azobis(2-amidinopropane) hydrochloride (AAPH) and hemin while barbaloin possessed weaker effects. A similar order of antioxidant potencies among the three compounds was observed on the lipid peroxidation of erythrocyte membranes in a tert-butylhydroperoxide (tBHP)/hemin oxidation system. On the other hand, barbaloin and rhapontin were comparatively stronger antioxidants than 6-gingerol in preventing AAPH-induced hemolysis of erythrocytes. Among the three compounds, only barbaloin protected Ca2+-ATPase and protein sulfhydryl groups on erythrocyte membranes against oxidative attack by tBHP/hemin. Interestingly, rhapontin demonstrated protective actions on Na+/K+-ATPase in a sulfhydryl group-independent manner under the same experimental conditions.. In view of their protective effects on LDL and erythrocytes against oxidative damage, these phenolic compounds might have potential applications in prooxidant state-related cardiovascular disorders.

Topics: Amidines; Animals; Anthracenes; Antioxidants; Cardiovascular Diseases; Catechols; Cells, Cultured; DNA Damage; Dose-Response Relationship, Drug; Erythrocyte Membrane; Fatty Alcohols; Hemolysis; Humans; Lipid Peroxidation; Lipoproteins, LDL; Male; Oxidation-Reduction; Phenols; Rats; Rats, Sprague-Dawley; Stilbenes

The mechanisms through which the consumption of alcoholic beverages, in particular wine, protects against cardiac and vascular diseases remain largely unexplored. New methods are needed to investigate that crucial medical and scientific question. Several groups are now beginning to use animal models of myocardial ischemia and reperfusion to explore whether certain nutrients, including ethanol and non-ethanolic components of wine, may have a specific protective effect on the myocardium, independently from the classical risk factors involved in vascular atherosclerosis and thrombosis. Concepts used in experimental cardiology, such as preconditioning and stunning, are now entering the field of nutrition, and this will undoubtedly lead to considerable improvements in the prevention and treatment of cardiovascular diseases.

Topics: Animals; Antioxidants; Cardiovascular Diseases; Humans; Resveratrol; Stilbenes; Wine

The phytochemical resveratrol, which is found in grapes and wine, has been reported to have a variety of anti-inflammatory, anti-platelet, and anti-carcinogenic effects. Based on its structural similarity to diethylstilbestrol, a synthetic estrogen, we examined whether resveratrol might be a phytoestrogen. At concentrations (approximately 3-10 microM) comparable to those required for its other biological effects, resveratrol inhibited the binding of labeled estradiol to the estrogen receptor and it activated transcription of estrogen-responsive reporter genes transfected into human breast cancer cells. This transcriptional activation was estrogen receptor-dependent, required an estrogen response element in the reporter gene, and was inhibited by specific estrogen antagonists. In some cell types (e.g., MCF-7 cells), resveratrol functioned as a superagonist (i.e., produced a greater maximal transcriptional response than estradiol) whereas in others it produced activation equal to or less than that of estradiol. Resveratrol also increased the expression of native estrogen-regulated genes, and it stimulated the proliferation of estrogen-dependent T47D breast cancer cells. We conclude that resveratrol is a phytoestrogen and that it exhibits variable degrees of estrogen receptor agonism in different test systems. The estrogenic actions of resveratrol broaden the spectrum of its biological actions and may be relevant to the reported cardiovascular benefits of drinking wine.

Topics: Breast Neoplasms; Cardiovascular Diseases; Cell Division; Estradiol; Estrogens, Non-Steroidal; Female; Genes, Reporter; Humans; Isoflavones; Organ Specificity; Phytoestrogens; Plant Preparations; Receptors, Estrogen; Resveratrol; Rosales; Stilbenes; Transcriptional Activation; Tumor Cells, Cultured; Wine

Resveratrol (trans-3,5,4'-trihydroxystilbene), a phenolic substance present in both grape skin and wines, is a phytoalexin involved in grey mould resistance. A new interest has surfaced in recent years related to the antioxidative actions of resveratrol, which in vivo could be related to the prevention of cardiovascular diseases linked to lipid metabolism, particularly HDL production, while the antifungal activity may be of interest in wine production technology. These aspects have led to the publication of a number of papers reporting data on the resveratrol content of several kind of wine: for Italian wines, it ranges between 0.5 and 10 ppm, depending on cultivar, area of cultivation, climate and wine-making technology. In this work, resveratrol was quantified in samples of two unusual Italian wines, Recioto (sweet) and Amarone (dry), produced with the same cultivar mixture in the same area (Valpolicella, Verona, Italy) and with the same grape conditioning technique. After resveratrol extraction, reversed-phase HPLC analysis was carried out and several elution conditions were tested. The resveratrol content of Recioto and Amarone wines was lower than the values reported in the literature for other wines, ranging between 0.05 and 0.8 ppm.

Topics: Cardiovascular Diseases; Chromatography, High Pressure Liquid; Desiccation; Fruit; Mitosporic Fungi; Plant Diseases; Reproducibility of Results; Resveratrol; Stilbenes; Wine

Some recent studies have put forward the hypothesis that the presence of trans-resveratrol (trans-3,5,4'-trihydroxystilbene) in red wine may be related to some of its therapeutic properties. A fundamental step in view of this evaluation is the development of a method for the quick, accurate and precise analysis of this compound. Sample enrichment and purification can be obtained by solid-phase extraction using reverse-phase C18 cartridges. HPLC analysis carried out by means of a photodiode-array detector, with an internal standard method, allows the detection of up to 10 micrograms/L in wine, with a linear range between 0.6 and 300 ng injected and a precision of 3.3%. The results of the first analyses show that the concentrations of trans-resveratrol in wines might be much higher than so far reported in the literature.

Topics: Cardiovascular Diseases; Chromatography, High Pressure Liquid; Humans; Italy; Resveratrol; Spectrophotometry, Ultraviolet; Stilbenes; Wine

Topics: Cardiovascular Diseases; Humans; Stilbenes; Tocopherols; Vitamin E