Resveratrol trial

Effects of Resveratrol on Diabetes Mellitus RV enhances the endothelial function, increases liver fatty acid oxidation, and decreases oxidative stress [ 49 ], leading to an improvement in insulin sensitivity [ 50 ].

Effect of Resveratrol on Cardiovascular Diseases Flow-mediated dilatation FMD of the brachial artery is a biomarker of endothelial function and cardiovascular health, with notable importance as an indicator of structural and functional endothelium changes [ 55 , 56 ]. Effect of Resveratrol on Obesity In a crossover study with 11 subjects, RV mimicked the effect of calorie restriction, reducing the metabolic rate, activating AMPK in muscle, and increasing the levels of SIRT1 and peroxisome proliferator-activated receptor gamma coactivator 1 alpha protein.

Figure 2. High-dose RV treatment showed a beneficial effect on both oxidative stress and some clinical outcome measures. RV plasma levels might be affected by metformin treatment; RV did not improve insulin sensitivity. Therefore, RV may help to decrease cardiovascular risk. Fasting glucose was unchanged, but postprandial glucose and three-hour glucose area under the curve decreased significantly. Insulin sensitivity using the Matsuda index improved.

Fasting lipid profile, CRP, and adiponectin were unchanged. Higher plasma RV concentration was associated with acute flow-mediated dilatation response. Lean and overweight, postmenopausal RV supplementation did not change plasma substrates and hormones glucose, plasma lipids, and insulin , adiponectin, leptin, CRP, and IL On three visits, the participants received two single-dose capsules. The capsules were combined to give the following treatments: 1 inert placebo, 2 mg t RV, and 3 mg t RV.

Healthy RV intake increased total-Hb and deoxy-Hb concentration, variables related to cerebral blood flow. High levels of sulfo- and glucuronide-conjugated RV compounds. Conclusions In this review, we have described the human clinical trials held in the last decade in which RV was determined in human plasma, urine, or feces.

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Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients. Dash S. Timmers S. This review discusses the currently available clinical data on resveratrol in the prevention, management, and treatment of various diseases and disorders. Based on the current evidence, the potential utility of this molecule in the clinic is discussed. Keywords: chronic diseases; clinical trial; nutraceutical; pharmacokinetics; resveratrol.

Abstract Resveratrol is a polyphenolic nutraceutical that exhibits pleiotropic activities in human subjects. Two separate experiments: 1 Follow-up: 2 months with 30 mg of RES in addition to oral contraceptive containing 3 mg drospiredone plus 30 ug ethinylestardiol previously taken for 6 months; 2 Follow-up: After submittion to laparoscopy and hysteroscopy for the management of endometriosis.

Sixteen patients on oral contraceptives alone for at least 2 months prior to hospital admission, while 26 were using them in combination with RES. Experiment 2: Effect on aromatase and cyclo-oxygenase-2 expression in endometrial tissue.

Inhibition of both aromatase and cyclo-oxygenase-2 expression was significantly greater in the eutopic endometrium of patients taking RES compared with oral contraceptives alone. Two-arm, unrandomized and unmarked phase 2 clinical trial. Follow up: 5g of SRT following breakfast for 20 days in a day cycle up to 12 cycles. Effect of SRT with or without bortezomib in multiple myeloma patients who had relapsed or were refractory to at least one prior therapy.

Significant hsCRP decrease in all groups at the d and d visits: Follow-up: 6 weeks daily ingestion of mg P. Effects on oxidative stress and inflammatory status. Placebo-uncontrolled, non-randomized, unblinded. Cohort with a single arm to evaluate effects after 4 weeks upon daily ingestion of 1 g RES capsules.

Four parallel arms, non-randomized, placebo uncontrolled. Blinded for analysis. Daily ingestion of 0. IGF-1 levels were decreased on the 2. Ingestion of a single dose of either a nutraceutical containing mg RES from P.

Effects were measured for 5 hours after meal. Effects on HFHC meal-induced oxidative and inflammatory stress. The highest effects occurred from 3 to 5 hours after meal. Randomized, crossover, double-blind trial, single dose, placebo-uncontrolled. Single ingestion of 30, 90, mg synthetic RES or placebo at weekly intervals. Analyses were performed 1 h after consumption of study products capsules. Randomized, crossover, double-blind, placebo-controlled trial.

Daily ingestion of mg synthetic RES for 1 month. To assess whether RES induce metabolic changes in obese men. RES induced modest but consistent metabolic changes that mimic calorie restriction. Randomized, crossover, double-blind, dose-response, placebo-controlled trial. Single intake of placebo, mg or mg RES. Analyses were performed 45 min after the ingestion. Acute effect on brain functions by improving blood flow. RES increased dose-dependently cerebral blood flow. Cognitive function was not affected.

Randomized, 3-arm, double-blind, placebo-controlled trial. Randomized, 3-arm, single-blind, placebo controlled trial. Comparison of study products on oxidative stress in obese subjects.

Low density microarrays in whole blood showed preliminary changes in some genes related to oxidative stress, mainly affected by CGSE and RTP. Non-randomized, placebo-uncontrolled, unblinded.

Daily consumption of 3 capsules to provide a total content of 6 mg RES, mg dried grape extract, mg of dried extract from olive oil, 9 mg lycopene, mg vitamin C and 90 mg bioflavonoids from citrus fruits. Follow-up: 5 days. Effects on against oxidative DNA-damage and alters their redox status.

Randomized, double-blind, placebo-controlled trial. Evaluate the metabolic effects in nonobese, postmenopausal women with normal glucose tolerance. No change in body composition, resting metabolic rate, plasma lipids, or inflammatory markers. No increase in liver, skeletal muscle, or adipose tissue insulin sensitivity. Randomized, placebo-controlled, double-blinded, and 2-arm parallel.

Follow up: either RES or placebo treatment for 4 weeks. Metabolic effects of high-dose RES in obese human subjects. Insulin sensitivity deteriorated insignificantly in both groups. No effect on blood pressure, resting energy expenditure, oxidation rates of lipid, ectopic or visceral fat content, or in inflammatory and metabolic biomarkers.

Randomized, double-blind, cross-over trial. Effects on markers of inflammation and oxidative stress in smokers. Uric acid, glucose, insulin, cholesterol, liver enzyme concentrations, and weight, waist circumference, and blood pressure values did not change significantly. Single-blind, vehicle-controlled, 1-arm trial. Therapeutic effects of RES on acneic skin. Global acne grading system GAGS score decreased by Histological analyses showed a decrease of No adverse effects were observed.

Topical application of 4 different moisturizing cream formulations on six sites on the non-exposed dorsal skin for 4 days. Histological analyses were blinded to the investigators. UV-induced erythema was mainly prevented by RTP and inhibited sunburn cell formation and melanin content. Randomized, unmasked, placebo-controlled trial. Follow up: 1 capsule of either placebo or a grape extract supplement mg containing 8 mg RES for 60 days.

Topical and systemic effects on age-related alterations to the skin, the skin antioxidant pool, and systemic oxidative stress levels. Systemic oxidative stress, plasmatic antioxidant capacity, and skin antioxidant power increased significantly. Skin moisturization and elasticity improved, while skin roughness and depth of wrinkles diminished.

Intensity of age spots decreased significantly. Non-medicated Subjects Healthy or at Risk for Disease Pharmaceutical drugs are prescribed by physicians and are consumed to treat mild or serious pathological processes. To Consume or not to Consume Resveratrol?

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Mechanisms involved in resveratrol-induced apoptosis and cell cycle arrest in prostate cancer-derived cell lines. J Androl. Resveratrol induces cell-cycle disruption and apoptosis in chemoresistant B16 melanoma. Resveratrol induces apoptosis and cell cycle arrest of human T24 bladder cancer cells in vitro and inhibits tumor growth in vivo.

Cancer Sci. Resveratrol suppresses human colon cancer cell proliferation and induces apoptosis via targeting the pentose phosphate and the talin-FAK signaling pathways-A proteomic approach. Proteome Sci. Trans-resveratrol inhibits the growth and induces the apoptosis of both normal and leukemic hematopoietic cells. Autophagy interplay with apoptosis and cell cycle regulation in the growth inhibiting effect of resveratrol in glioma cells.

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Free Radic Biol Med. Resveratrol enhances prostate cancer cell response to ionizing radiation. Radiat Oncol.

Resveratrol arrests cell cycle and induces apoptosis in human hepatocellular carcinoma Huh-7 cells. J Med Food. Int J Cancer. Mitochondria as the primary target of resveratrol-induced apoptosis in human retinoblastoma cells. Invest Ophthalmol Vis Sci. Mol Cancer Ther. Resveratrol induces apoptosis associated with mitochondrial dysfunction in bladder carcinoma cells. Int J Urol. Resveratrol inhibits proliferation induces apoptosis and overcomes chemoresistance through down-regulation of STAT3 and nuclear factor-kappaB-regulated antiapoptotic and cell survival gene products in human multiple myeloma cells.

Inhibition of phosphatidylinositol 3-kinase-mediated glucose metabolism coincides with resveratrol-induced cell cycle arrest in human diffuse large B-cell lymphomas. Biochem Pharmacol. Hum Mol Genet. Exp Toxicol Pathol. Resveratrol induces growth arrest and apoptosis through activation of FOXO transcription factors in prostate cancer cells. Resveratrol enhances the anti-tumor activity of the mTOR inhibitor rapamycin in multiple breast cancer cell lines mainly by suppressing rapamycin-induced AKT signaling.

Cancer Lett. J Biol Chem. Resveratrol-induced apoptosis in MCF-7 human breast cancer cells involves a caspase-independent mechanism with downregulation of Bcl-2 and NF-kappaB. Resveratrol inhibits tumor necrosis factor-alpha-mediated matrix metalloproteinase-9 expression and invasion of human hepatocellular carcinoma cells.

Biomed Pharmacother. Low concentrations of resveratrol inhibit Wnt signal throughput in colon-derived cells implications for colon cancer prevention. BMC Cancer. Peroxisome proliferator-activated receptor gamma as a molecular target of resveratrol-induced modulation of polyamine metabolism. Endocytosis of resveratrol via lipid rafts and activation of downstream signaling pathways in cancer cells.

Cancer Prev Res. Resveratrol reduces the invasive growth and promotes the acquisition of a long-lasting differentiated phenotype in human glioblastoma cells. Evaluation of anti-invasion effect of resveratrol and related methoxy analogues on human hepatocarcinoma cells.

Drug Target Insights. Resveratrol inhibits the epidermal growth factor-induced epithelial mesenchymal transition in MCF-7 cells. Bournival J, Quessy P. Martinoli MG. Cell Mol Neurobiol. Neuroprotective effects of resveratrol against beta-amyloid-induced neurotoxicity in rat hippocampal neurons: involvement of protein kinase C.

Br J Pharmacol. Resveratrol promotes clearance of Alzheimer's disease amyloid-beta peptides. AMP-activated protein kinase signaling activation by resveratrol modulates amyloid-beta peptide metabolism. Resveratrol scavenges reactive oxygen species and effects radical-induced cellular responses. Biochem Biophys Res Commun. J Appl Physiol. Resveratrol protects dopamine neurons against lipopolysaccharide-induced neurotoxicity through its anti-inflammatory actions.

Mol Pharmacol. J Physiol Pharmacol. Resveratrol reverses endothelial nitric-oxide synthase uncoupling in apolipoprotein E knockout mice.

J Pharmacol Exp Ther. Resveratrol attenuates mitochondrial oxidative stress in coronary arterial endothelial cells. Induction of manganese superoxide dismutase by nuclear translocation and activation of SIRT1 promotes cell survival in chronic heart failure. Resveratrol enhances neovascularization in the infarcted rat myocardium through the induction of thioredoxin-1 heme oxygenase-1 and vascular endothelial growth factor.

J Mol Cell Cardiol. Potential mechanism by which resveratrol a red wine constituent protects neurons. Resveratrol alleviates cardiac dysfunction in streptozotocin-induced diabetes role of nitric oxide thioredoxin and heme oxygenase. Mechanism of concentration-dependent induction of heme oygenase-1 by resveratrol in human aortic smooth muscle cells. Effects of resveratrol on NO secretion stimulated by insulin and its dependence on SIRT1 in high glucose cultured endothelial cells. Takahashi S, Nakashima Y.

Repeated and long-term treatment with physiological concentrations of resveratrol promotes NO production in vascular endothelial cells. Resveratrol stimulates nitric oxide production by increasing estrogen receptor alpha-Src-caveolin-1 interaction and phosphorylation in human umbilical vein endothelial cells.

Resveratrol induces mitochondrial biogenesis in endothelial cells. Resveratrol a polyphenolic phytoalexin present in red wine enhances expression and activity of endothelial nitric oxide synthase. Resveratrol and estradiol rapidly activate MAPK signaling through estrogen receptors alpha and beta in endothelial cells.

Resveratrol prevents hyperglycemia-induced endothelial dysfunction via activation of adenosine monophosphate-activated protein kinase.

Bio-chem Biophys Res Commun. Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. Resveratrol confers endothelial protection via activation of the antioxidant transcription factor Nrf2. Resveratrol suppresses tumor necrosis factor-alpha-induced fractalkine expression in endothelial cells. Resveratrol attenuates TNF-alpha-induced activation of coronary arterial endothelial cells: role of NF-kappaB inhibition.

Resveratrol inhibits monocytic cell chemotaxis to MCP-1 and prevents spontaneous endothelial cell migration through Rho kinase-dependent mechanism. J Atheroscler Thromb. Vasoprotective effects of resveratrol and SIRT1attenuation of cigarette smoke-induced oxidative stress and proin-flammatory phenotypic alterations. In vitro effect of resveratrol against oxidative injury of human coronary artery endothelial cells. Turk J Med Sci.

Chemopreventive properties of trans-resveratrol are associated with inhibition of activation of the IkappaB kinase. Regulation of proliferation and gene expression in cultured human aortic smooth muscle cells by resveratrol and standardized grape extracts. Activity in vitro of resveratrol on granulocyte and monocyte adhesion to endothelium. Resveratrol inhibits cyclooxygenase-2 transcription and activity in phorbol ester-treated human mammary epithelial cells.

The antioxidant resveratrol protects against chondrocyte apoptosis via effects on mitochondrial polarization and ATP production. Arthritis Rheum. Sirt1 promotes fat mobilization in white adipocytes by repressing PPARgamma. Resveratrol induces apoptosis and inhibits adipogenesis in 3T3-L1 adipocytes.

Phytotherapy Res. Resveratrol a naturally occurring diphenolic compound affects lipogenesis lipolysis and the antilipolytic action of insulin in isolated rat adipocytes. J Steroid Biochem Mol Biol. Resveratrol regulates human adipocyte number and function in a Sirt1-dependent manner. Identification of a novel proapoptotic function of resveratrol in fat cells.

Faseb J. Delipidating effect of resveratrol metabolites in 3T3-L1 adipocytes. Br J Haematol. Resveratrol attenuates thromboxane A2 receptor agonist induced platelet activation by reducing phospholipase C activity.

Eur J Pharmacol. Mechanisms of resveratrol induced platelet apoptosis. Cardiovasc Res. The effect of resveratrol on a cell model of human aging. J Nutr Biochem. Oxidative stress modulates Sir2alpha in rat hippocampus and cerebral cortex. Eur J Neurosci. Effect of resveratrol on growth of 4T1 breast cancer cells in vitro and in vivo. Br J Cancer. Resveratrol given intraperitoneally does not inhibit the growth of high-risk t 4. Int J Oncol. Resveratrol exerts differential effects in vitro and in vivo against ovarian cancer cells.

Asian Pac J Cancer Prev. Resveratrol a natural product present in wine decreases tumor growth in a rat tumor model. Inhibition of cancer growth by resveratrol is related to its low bioavailability. Suppression of prostate cancer growth by resveratrol in the transgenic rat for adenocarcinoma of prostate TRAP model. Anticancer activity of resveratrol on implanted human primary gastric carcinoma cells in nude mice.

World J Gastroenterol. CNS Neurosci Ther. Resveratrol inhibits growth of orthotopic pancreatic tumors through activation of FOXO transcription factors. Bishayee A, Dhir N. Resveratrol-mediated chemoprevention of diethylnitrosamine-initiated hepatocarcinogenesis inhibition of cell proliferation and induction of apoptosis. Chem Biol Interact. Caveolin-I enhances resveratrol-mediated cytotoxicity and transport in a hepatocellular carcinoma model. J Transl Med. Pharm Res. Alteration of hepatic proinflammatory cytokines is involved in the resveratrol-mediated chemoprevention of chemically-induced hepatocarcinogenesis.

Curr Pharm Biotechnol. Resveratrol prevents inflammation-dependent hepatic melanoma metastasis by inhibiting the secretion and effects of inter-leukin Induction of proteasome expression in skeletal muscle is attenuated by inhibitors of NF-kappaB activation. Effect of resveratrol on the metastasis of 4T1 mouse breast cancer cells in vitro and in vivo. Nutr Res Pract. Suppression of 7,dimethylbenz a anthracene-induced mammary carcinogenesis in rats by resveratrol. Role of nuclear factor-kappa B cyclooxygenase 2 and matrix metalloprotease 9.

Can-cer Res. Effect of resveratrol and in combination with 5-FU on murine liver cancer. Resveratrol attenuates the anticancer efficacy of paclitaxel in human breast cancer cells in vitro and in vivo. Eur J Cancer. Prominent chemopreventive and chemoenhancing effects for resveratrol unraveling molecular targets and the role of C-reactive protein.

Resveratrol depresses the growth of colorectal aberrant crypt foci by affecting bax and p21 CIP expression. Sengottuvelan M, Nalini N. Dietary supplementation of resveratrol suppresses colonic tumor incidence in 1. Chemoprevention of benzo a pyrene-induced colon polyps in Apc Min mice by resveratrol. Resveratrol attenuates doxorubicin-induced cellular damage by modulating nitric oxide and apoptosis. Resveratrol preconditioning induces cellular stress proteins and is mediated via NMDA and estrogen receptors.

Cardioprotection by resveratrol: a novel mechanism via autophagy involving the mTORC2 pathway. Insulin and resveratrol act synergistically preventing cardiac dysfunction in diabetes, but the advantage of resveratrol in diabetics with acute heart attack is antagonized by insulin.

Resveratrol protects myocardial ischemia-reperfusion injury through both NO-dependent and NO-independent mechanisms. Resveratrol a unique phytoalexin present in red wine delivers either survival signal or death signal to the ischemic myocardium depending on dose. Resveratrol improves myocardial perfusion in a swine model of hypercholesterolemia and chronic myocardial ischemia. A dietary resveratrol-rich grape extract prevents the developing of atherosclerotic lesions in the aorta of pigs fed an atherogenic diet.

Resveratrol treatment reduces cardiac progenitor cell dysfunction and prevents morpho-functional ventricular remodeling in type-1 diabetic rats. Resveratrol induces mitochondrial biogenesis and ameliorates Ang II-induced cardiac remodeling in transgenic rats harboring human renin and angiotensinogen genes.

Blood Press. Resveratrol improves cardiovascular function in DOCA-salt hypertensive rats. Female rats fed a high-fat diet were associated with vascular dysfunction and cardiac fibrosis in the absence of overt obesity and hyperlipidemia therapeutic potential of resveratrol. Long-term resveratrol administration reduces metabolic disturbances and lowers blood pressure in obese Zucker rats.

Chronic administration of resveratrol prevents biochemical cardiovascular changes in fructose-fed rats. Am J Hypertens. Resveratrol prevents endothelial nitric oxide synthase uncoupling and attenuates development of hypertension in spontaneously hypertensive rats. Resveratrol downregulates acute pulmonary thromboembolism-induced pulmonary artery hypertension via p38 mitogen-activated protein kinase and monocyte chemoattractant protein-1 signaling in rats.

Life Sci. High-fructose corn syrup causes vascular dysfunction associated with metabolic disturbance in rats protective effect of resveratrol. Food Chem Toxicol. Resveratrol and small artery compliance and remodeling in the spontaneously hypertensive rat. Resveratrol prevents the development of pathological cardiac hypertrophy and contractile dysfunction in the SHR without lowering blood pressure.

Treatment with low-dose resveratrol reverses cardiac impairment in obese prone but not in obese resistant rats. Resveratrol improves survival, hemodynamics and energetics in a rat model of hypertension leading to heart failure. Resveratrol reduces infarct size and improves ventricular function after myocardial ischemia in rats. Statin and resveratrol in combination induces cardioprotection against myocardial infarction in hypercholes-terolemic rat. Resveratrol preserves cardiac function, but does not prevent endothelial dysfunction or pulmonary inflammation after environmental tobacco smoke exposure.

Resveratrol arrests and regresses the development of pressure overload but not volume overload-induced cardiac hy-pertrophy in rats. Resveratrol prevents the prohypertrophic effects of oxidative stress on LKB1. Sirt1 acts in association with PPARa to protect the heart from hypertrophy metabolic dysregulation and inflammation. Car-diovasc Res. Resveratrol attenuates ovariectomy-induced hypertension and bone loss in stroke-prone spontaneously hypertensive rats. J Nutr Sci Vitaminol. Protective effect of ferulic acid and resveratrol against alloxan-induced diabetes in mice.

Resveratrol ameliorates oxidative DNA damage and protects against acrylamide-induced oxidative stress in rats. Mol Biol Rep. Attenuation of insulin resistance metabolic syndrome and hepatic oxidative stress by resveratrol in fructose-fed rats.

Resveratrol attenuates oxidative stress and prevents steatosis and hypertension in obese rats programmed by early weaning. J Nutr Biochem