stilbenes and Vascular-Diseases

Vascular metabolic dysfunction presents in various diseases, such as atherosclerosis, hypertension, and diabetes mellitus. Due to the high prevalence of these diseases, it is important to explore treatment strategies to protect vascular function. Resveratrol (RSV), a natural polyphenolic phytochemical, is regarded as an agent to regulate metabolic pathways. Many studies have proven that RSV has beneficial effects on improving metabolism in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), which provide new directions to treat vascular metabolic diseases. Herein, we overviewed that RSV could regulate cell metabolism activity by inhibiting glucose uptake, suppressing glycolysis, preventing cells from fatty acid-related damages, reducing lipogenesis, increasing fatty acid oxidation, enhancing lipolysis, elevating uptake and synthesis of glutamine, and increasing NO release. Furthermore, in clinical trials, although the results from different studies remain controversial, we proposed that RSV had better therapeutic effects at high concentrations and for patients with metabolic disorders.

Topics: Endothelial Cells; Fatty Acids; Humans; Lipid Metabolism; Metabolic Diseases; Resveratrol; Stilbenes; Vascular Diseases

Although reactive oxygen species (ROS) such as superoxide, hydrogen peroxide and hydroxyl radical are generated as the natural byproduct of normal oxygen metabolism, they can create oxidative damage via interaction with bio-molecules. The role of oxidative stress as a remarkable upstream part is frequently reported in the signaling cascade of inflammation as well as chemo attractant production. Even though hydrogen peroxide can control cell signaling and stimulate cell proliferation at low levels, in higher concentrations it can initiate apoptosis and in very high levels may create necrosis. So far, the role of ROS in cellular damage and death is well documented with implicating in a broad range of degenerative alterations e.g. carcinogenesis, aging and other oxidative stress related diseases (OSRDs). Reversely, it is cleared that antioxidants are potentially able to suppress (at least in part) the immune system and to enhance the normal cellular protective responses to tissue damage. In this review, we aimed to provide insights on diverse OSRDs, which are correlated with the concept of oxidative stress as well as its cellular effects that can be inhibited by antioxidants. Resveratrol, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, statins, nebivolol and carvedilol, pentaerythritol tetranitrate, mitochondria-targeted antioxidants, and plant-derived drugs (alone or combined) are the potential medicines that can be used to control OSRD.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Antioxidants; Benzopyrans; Carbazoles; Carvedilol; Diabetes Mellitus; Disease Models, Animal; Ethanolamines; Humans; Hydrogen Peroxide; Inflammatory Bowel Diseases; Nebivolol; Neoplasms; Neurodegenerative Diseases; Osteoporosis; Oxidative Stress; Propanolamines; Reactive Oxygen Species; Resveratrol; Stilbenes; Vascular Diseases

This review focuses on molecular, cellular, and functional changes that occur in the vasculature during aging; explores the links between mitochondrial oxidative stress, inflammation, and development of vascular disease in the elderly patients; and provides a landscape of molecular mechanisms involved in cellular oxidative stress resistance, which could be targeted for the prevention or amelioration of unsuccessful vascular aging. Practical interventions for prevention of age-associated vascular dysfunction and disease in old age are considered here based on emerging knowledge of the effects of anti-inflammatory treatments, regular exercise, dietary interventions, and caloric restriction mimetics.

Topics: Aging; Animals; Apoptosis; Atherosclerosis; Blood Vessels; Caloric Restriction; Endothelium, Vascular; Exercise; Humans; Inflammation; Oxidative Stress; Resveratrol; Stem Cells; Stilbenes; Vascular Diseases

Growing evidence from tissue culture, animal, and clinical models suggests that the flavonoid-rich fruits of the North American cranberry and blueberry (Vaccinium spp.) have the potential ability to limit the development and severity of certain cancers and vascular diseases including atherosclerosis, ischemic stroke, and neurodegenerative diseases of aging. The fruits contain a variety of phytochemicals that could contribute to these protective effects, including flavonoids such as anthocyanins, flavonols, and proanthocyanidins; substituted cinnamic acids and stilbenes; and triterpenoids such as ursolic acid and its esters. Cranberry and blueberry constituents are likely to act by mechanisms that counteract oxidative stress, decrease inflammation, and modulate macromolecular interactions and expression of genes associated with disease processes. The evidence suggests a potential role for dietary cranberry and blueberry in the prevention of cancer and vascular diseases, justifying further research to determine how the bioavailability and metabolism of berry phytonutrients influence their activity in vivo.

Topics: Animals; Anthocyanins; Anticarcinogenic Agents; Antioxidants; Atherosclerosis; Blueberry Plants; Flavonoids; Humans; Neoplasms; Phytotherapy; Proanthocyanidins; Stilbenes; Stroke; Triterpenes; Vaccinium macrocarpon; Vascular Diseases

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

Perivascular adipose tissue (PVAT) releases several adipo(cyto)kines. Some are vasoactive substances that elicit a net beneficial anticontractile effect. Resveratrol and testosterone are known to modulate adipo(cyto)kine release from adipose tissue and could therefore influence the anticontractile effect of PVAT. In vitro tension measurements were performed using thoracic aorta segments with and without adipose tissue from sham-operated or orchidectomized male Swiss mice. Concentration-response curves to norepinephrine (NOR) were constructed in the presence and absence of resveratrol (10 μM, 15 min) or the relaxant effect of resveratrol (10-100 μM) was investigated after inducing tone with NOR (5 μM). Aortas with PVAT displayed significantly attenuated contractions to NOR compared with aortas without PVAT. In aortas without PVAT, resveratrol (10 μM) significantly decreased NOR responses and elicited concentration-dependent (10-100 µM) relaxations. However, in aortas with adherent PVAT, resveratrol (10 μM) neither decreased NOR responses, nor did resveratrol (10-100 µM) induce arterial relaxations. The anticontractile effect of PVAT was less pronounced in the presence of resveratrol and unaltered by orchidectomy. Orchidectomy did not influence contractions induced by NOR. Orchidectomy does not modulate the anticontractile capacity of PVAT, while resveratrol decreases the vasorelaxing influence of PVAT. The positive effects associated with resveratrol addition are neutralized by the presence of PVAT. This is thought to result from a dual effect of resveratrol: (1) inhibition of the influence of vasodilatory adipo(cyto)kines and (2) a direct relaxant effect on the vascular smooth muscle. Overall, the beneficial relaxing effect of resveratrol is lost in mice thoracic aorta surrounded by PVAT.

Topics: Adipose Tissue; Animals; Aorta, Thoracic; Disease Models, Animal; Male; Mice; Muscle, Smooth, Vascular; Orchiectomy; Platelet Aggregation Inhibitors; Resveratrol; Stilbenes; Vascular Diseases; Vasoconstriction; Vasodilation

Aging leads to increased insulin resistance and arterial dysfunction, with oxidative stress playing an important role. This study explored the metabolic and arterial effects of a chronic treatment with resveratrol, an antioxidant polyphenol compound that has been shown to restore insulin sensitivity and decrease oxidative stress, in old mice with or without a high-protein diet renutrition care. High-protein diet tended to increase insulin resistance and atheromatous risk. Resveratrol improved insulin sensitivity in old mice fed standard diet by decreasing homeostasis model of assessment-insulin resistance and resistin levels. However, resveratrol did not improve insulin resistance status in old mice receiving the high-protein diet. In contrast, resveratrol exhibited deleterious effects by increasing inflammation state and superoxide production and diminishing aortic distensibility. In conclusion, we demonstrate that resveratrol has beneficial or deleterious effects on insulin sensitivity and arterial function, depending on nutritional status in our models.

Topics: Aging; Animals; Antioxidants; Aorta; Blood Glucose; Chemokine CCL5; Chemokine CXCL1; Dietary Proteins; Disease Models, Animal; Insulin Resistance; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Nutritional Status; Oxidative Stress; Phenols; Resistin; Resveratrol; Ribonucleotide Reductases; Serum Albumin; Stilbenes; Superoxides; Tumor Necrosis Factor-alpha; Vascular Capacitance; Vascular Diseases; Vasodilation

Studying human vascular disease in conventional cell cultures and in animal models does not effectively mimic the complex vascular microenvironment and may not accurately predict vascular responses in humans. We utilized a microfluidic device to recapitulate both shear stress and O2 levels in health and disease, establishing a microfluidic vascular model (μVM). Maintaining human endothelial cells (ECs) in healthy-mimicking conditions resulted in conversion to a physiological phenotype namely cell elongation, reduced proliferation, lowered angiogenic gene expression and formation of actin cortical rim and continuous barrier. We next examined the responses of the healthy μVM to a vasotoxic cancer drug, 5-Fluorouracil (5-FU), in comparison with an in vivo mouse model. We found that 5-FU does not induce apoptosis rather vascular hyperpermeability, which can be alleviated by Resveratrol treatment. This effect was confirmed by in vivo findings identifying a vasoprotecting strategy by the adjunct therapy of 5-FU with Resveratrol. The μVM of ischemic disease demonstrated the transition of ECs from a quiescent to an activated state, with higher proliferation rate, upregulation of angiogenic genes, and impaired barrier integrity. The μVM offers opportunities to study and predict human ECs with physiologically relevant phenotypes in healthy, pathological and drug-treated environments.

Topics: Animals; Atherosclerosis; Capillary Permeability; Endothelial Cells; Endothelium, Vascular; Fluorouracil; Humans; Ischemia; Mice; Microfluidic Analytical Techniques; Oxygen Consumption; Resveratrol; Stilbenes; Stress, Mechanical; Vascular Diseases

The aim of this study was to evaluate the effect of smokeless tobacco extract on ovariectomized female rats and to investigate the role of resveratrol in alleviating associated vascular and diabetic complications.. Thirty-six female Wistar rats (8 wk old) were subjected to bilateral ovariectomy (OVX) or sham operation and randomly assigned to six groups: sham operation; OVX; OVX + aqueous extract of smokeless tobacco (AEST); OVX + AEST + 17β-estradiol; OVX + AEST + resveratrol 25 mg/kg/day PO; and OVX + AEST + resveratrol 50 mg/kg/day PO. All treatments were given for 60 days. Various vascular and metabolic markers (such as serum glucose, triglycerides, cholesterol, insulin, estradiol, glycosylated hemoglobin, glucose tolerance), ex vivo vascular reactivity of aortic ring, and aortic collagen levels were estimated after the treatments.. Oral exposure to smokeless tobacco extract in ovariectomized female rats triggered a significant increase in metabolic markers (viz, serum triglycerides, cholesterol, glucose, insulin, glycosylated hemoglobin), and aortic collagen levels. It also led to decreased serum nitrate-nitrite levels and vascular reactivity. Resveratrol 50 mg/kg/day PO attenuated detrimental changes in aortic reactivity and aortic collagen levels, improved glucose tolerance, and reversed the deleterious effects on other serum parameters comparable to 17β-estradiol.. Resveratrol treatment for 60 days abrogates the deleterious effects of smokeless tobacco on ovariectomized female rats. Resveratrol in adequate doses can be effectively used as an alternative to estrogen therapy for smokeless tobacco-induced vascular and diabetic complications.

Topics: Animals; Aorta; Collagen; Diabetes Complications; Diabetes Mellitus; Estradiol; Female; Glucose Tolerance Test; Insulin; Metabolic Diseases; Nitrates; Nitrites; Ovariectomy; Rats; Rats, Wistar; Resveratrol; Stilbenes; Tobacco, Smokeless; Vascular Diseases

The combination of a lipid-lowering diet and scientifically proven nutraceutical supplements has the ability to significantly reduce low-density lipoprotein (LDL) cholesterol, increase LDL particle size, decrease LDL particle number, lower trigylcerides and very LDL levels, and increase total and high-density lipoprotein 2b cholesterol. In addition, inflammation, oxidative stress, and immune responses are decreased. In several prospective clinical trials, coronary heart disease and cardiovascular disease have been reduced with many nutraceutical supplements. This nutritional and nutraceutical supplement treatment is a valid alternative for patients who are intolerant to statins, cannot take other drugs for the treatment of dyslipidemia, or prefer alternative treatments. This new approach to lipid management to decrease vascular disease utilizes a functional medicine approach with a broader treatment program that will address the multitude of steps involved in lipid-induced vascular damage.

Topics: Atherosclerosis; Dietary Fats; Dietary Supplements; Dyslipidemias; Humans; Lipoproteins; Lipoproteins, VLDL; Oxidative Stress; Pantetheine; Resveratrol; Stilbenes; Tocotrienols; Triglycerides; Vascular Diseases; Vasodilator Agents

High-fructose corn syrup (HFCS) is used in many prepared foods and soft drinks. However, limited data is available on the consequences of HFCS consumption on metabolic and cardiovascular functions. This study was, therefore, designed to assess whether HFCS drinking influences the endothelial and vascular function in association with metabolic disturbances in rats. Additionally, resveratrol was tested at challenge with HFCS. We investigated the effects of HFCS (10% and 20%) and resveratrol (50mg/l) beverages on several metabolic parameters as well as endothelial relaxation, vascular contractions, expressions of endothelial nitric oxide synthase (eNOS), sirtuin 1 (SIRT1), gp91(phox) and p22(phox) proteins and superoxide generation in the aortas. Consumption of HFCS (20%) increased serum triglyceride, VLDL and insulin levels as well as blood pressure. Impaired relaxation to acetylcholine and intensified contractions to phenylephrine and angiotensin II were associated with decreased eNOS and SIRT1 whereas increased gp91(phox) and p22(phox) proteins, along with provoked superoxide production in the aortas from HFCS-treated rats. Resveratrol supplementation efficiently restored HFCS-induced deteriorations. Thus, intake of HFCS leads to vascular dysfunction by decreasing vasoprotective factors and provoking oxidative stress in association with metabolic disturbances. Resveratrol has a protective potential against the harmful consequences of HFCS consumption.

Topics: Animals; Antioxidants; Aorta, Thoracic; Blood Glucose; Blood Pressure; Blotting, Western; Body Weight; Fructose; Insulin; Lipids; Male; NADPH Oxidases; Nitric Oxide; Phenylephrine; Rats; Rats, Wistar; Resveratrol; Signal Transduction; Sirtuin 1; Stilbenes; Superoxides; Vascular Diseases; Vasoconstrictor Agents

Resveratrol has been shown to have vasoprotective effects by upregulating oxidative defense mechanisms in a variety of pathophysiological conditions. However, the effect of resveratrol on diabetic oxidative stress and vascular and metabolic abnormalities is not completely understood. Therefore, this study was designed to evaluate whether long-term resveratrol supplementation has a protective effect on vascular function and integrity in association with metabolic parameters and oxidative stress in insulin-dependent diabetes.. Diabetes was induced in rabbits with alloxan and maintained for 8 weeks. We used a resveratrol dose of 5 mg/L (10 weeks, starting 14 days before alloxan injection) and 50 mg/L (8 or 10 weeks, starting concomitantly or 14 days before alloxan injection) in the drinking water of rabbits.. Relaxation to acetylcholine was impaired (control 75.6 ± 3.59%, versus diabetic 42.23 ± 2.53%) and contractions to phenylephrine increased (control 136.89 ± 2.27%, versus diabetic 159.37 ± 6.27%) in aortas from diabetic animals. These changes were associated with increased basal or NAD(P)H-induced superoxide production, as well as lipid peroxide and superoxide dismutase (SOD) levels in the aortic samples. The maximal relaxation to acetylcholine improved by 75.74 ± 9.04% in diabetic rabbits treated with resveratrol. The increased contractions to phenylephrine were not restored to control values after resveratrol treatments, but sensitivity to the contractions tended to decrease. Resveratrol increased nitrite/nitrate levels and suppressed basal or NAD(P)H-induced superoxide production and lipid peroxide levels in the aortas. Importantly, resveratrol increased serum insulin levels without affecting blood glucose and the lipid profile in diabetic rabbits. Using electron microscopic examinations, resveratrol was found to markedly protect the endothelial integrity from diabetes.. Overall, there was no noticeable difference between resveratrol treatment groups on the recovery from diabetes. Our results indicate that resveratrol alleviates type 1 diabetes-induced vasculopathy by decreasing vascular oxidative stress and thereby increasing the bioavailability of nitric oxide without changing metabolic abnormalities.

Topics: Acetylcholine; Animals; Antioxidants; Blood Glucose; Body Weight; Catalase; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Estrogens; Insulin; Lipid Peroxides; Lipids; Male; NADP; Nitric Oxide; Nitric Oxide Synthase Type III; Oxidative Stress; Rabbits; Resveratrol; Stilbenes; Superoxide Dismutase; Testosterone; Time Factors; Vascular Diseases

Topics: Animals; Antioxidants; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Male; Oxidative Stress; Resveratrol; Stilbenes; Vascular Diseases

Recent studies have shown that resveratrol (3,5,4'-trihydroxystilbene), a polyphenolic compound found in grapes and red wine, has various beneficial effects on cardiovascular diseases and prolongs the life span of mice fed a high-fat diet. We hypothesized that resveratrol may attenuate vascular inflammatory response induced by angiotensin (Ang) II. We examined the effect of resveratrol on Ang II-induced interleukin (IL)-6 expression in vascular smooth muscle cells (VSMCs). Resveratrol significantly attenuated Ang II-induced IL-6 mRNA expression and IL-6 protein in the supernatant of VSMC in a dose-dependent manner. Resveratrol suppressed the IL-6 gene promoter activity. Resveratrol inhibited the Ang II-induced cAMP-response element-binding protein and nuclear factor-kappa B activity, which are critical for Ang II-induced IL-6 gene activation. An increase in the serum concentration of IL-6 induced by Ang II infusion was attenuated by an oral administration of resveratrol. Resveratrol also inhibited Ang II-induced hypertension and perivascular fibrosis of the heart. Although hydralazine reduced blood pressure level equal to resveratrol, it did not reduce the Ang II-induced IL-6 production and perivascular fibrosis. These data suggest that the inhibition of Ang II-induced vascular inflammation and high blood pressure by resveratrol may contribute, at least in part, to the anti-atherogenic effects of resveratrol.

Topics: Angiotensin II; Animals; Antioxidants; Blood Pressure; Blotting, Northern; Blotting, Western; Body Weight; Cells, Cultured; DNA; Electrophoretic Mobility Shift Assay; Enzyme-Linked Immunosorbent Assay; Fibrosis; Heart Rate; Interleukin-6; Luciferases; Mice; Mice, Inbred C57BL; Muscle, Smooth, Vascular; Promoter Regions, Genetic; Rats; Resveratrol; Stilbenes; Vascular Diseases