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1.
Chemoprevention by resveratrol and pterostilbene: Targeting on epigenetic regulation.
Lee, PS, Chiou, YS, Ho, CT, Pan, MH
BioFactors (Oxford, England). 2018;(1):26-35
Abstract
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.
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2.
No Beneficial Effects of Resveratrol on the Metabolic Syndrome: A Randomized Placebo-Controlled Clinical Trial.
Kjær, TN, Ornstrup, MJ, Poulsen, MM, Stødkilde-Jørgensen, H, Jessen, N, Jørgensen, JOL, Richelsen, B, Pedersen, SB
The Journal of clinical endocrinology and metabolism. 2017;(5):1642-1651
Abstract
CONTEXT Low-grade inflammation is associated with obesity and the metabolic syndrome (MetS). Preclinical evidence suggests that resveratrol (RSV) has beneficial metabolic and anti-inflammatory effects that could have therapeutic implications. OBJECTIVE To investigate effects of long-term RSV treatment on inflammation and MetS. SETTING AND DESIGN A randomized, placebo-controlled, double-blind, parallel group clinical trial conducted at Aarhus University Hospital. PARTICIPANTS Middle-aged community-dwelling men (N = 74) with MetS, 66 of whom completed all visits (mean ± standard error of the mean): age, 49.5 ± 0.796 years; body mass index, 33.8 ± 0.44 kg/m2; waist circumference, 115 ± 1.14 cm. INTERVENTION Daily oral supplementation with 1000 mg RSV (RSVhigh), 150 mg RSV, or placebo for 16 weeks. MAIN OUTCOME MEASURES Plasma levels of high-sensitivity C-reactive protein (hs-CRP), circulating lipids, and inflammatory markers in circulation and adipose/muscle tissue biopsy specimens; glucose metabolism; and body composition including visceral fat and ectopic fat deposition. RESULTS RSV treatment did not lower circulating levels of hs-CRP, interleukin 6, or soluble urokinase plasminogen activator receptor in plasma, and inflammatory gene expression in adipose and muscle tissues also remained unchanged. RSV treatment had no effect on blood pressure, body composition, and lipid deposition in the liver or striated muscle. RSV treatment had no beneficial effect on glucose or lipid metabolism. RSVhigh treatment significantly increased total cholesterol (P < 0.002), low-density lipoprotein (LDL) cholesterol (P < 0.006), and fructosamine (P < 0.013) levels compared with placebo. CONCLUSION RSV treatment did not improve inflammatory status, glucose homeostasis, blood pressure, or hepatic lipid content in middle-aged men with MetS. On the contrary, RSVhigh significantly increased total cholesterol, LDL cholesterol, and fructosamine levels compared with placebo.
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3.
The Effects of Resveratrol Supplementation in Overweight and Obese Humans: A Systematic Review of Randomized Trials.
Christenson, J, Whitby, SJ, Mellor, D, Thomas, J, McKune, A, Roach, PD, Naumovski, N
Metabolic syndrome and related disorders. 2016;(7):323-33
Abstract
BACKGROUND Obesity and metabolic syndrome are significant global health issues, with current public health messages predominately focused on altering dietary and physical activity behaviors. Resveratrol is a polyphenol (stilbenoid) commonly found in grapes, and human trials to date have shown conflicting and limited beneficial effects with respect to health. The aim of this study was to determine the effect of resveratrol supplementation on reducing body weight and modifying associated inflammatory markers. METHODS A systematic review was undertaken following the PRISMA guidelines and using five indexed databases (OVID MEDLINE, Cochrane Library, Web of Science, SCOPUS, and CINAHL). A search strategy was formulated to select randomized, double-blind, placebo-controlled human trials investigating the effects of resveratrol supplementation on obesity or overweight, including body weight, metabolic and inflammatory markers. RESULTS Five thousand five hundred sixty-nine studies published from 1990 to November 2015 were identified, with only nine papers meeting the inclusion criteria. The studies involved 208 participants (aged 49.2 ± 8.3 years) and utilized a substantial range of resveratrol doses (75-3000 mg/day). Study durations were a minimum of 2 weeks (14-90 days). Seven studies indicated no significant change in body mass index or body weight (P > 0.05), and three studies showed no improvements in fat mass, fat volume, or abdominal fat distribution (P > 0.05). Four studies included measurements of inflammatory markers, with three of these finding resveratrol supplementation to have a significant positive effect (P > 0.05). CONCLUSION Based on the included studies, there is currently insufficient evidence to support the recommendation of resveratrol supplements in management of obesity. However, there were significant but not entirely consistent anti-inflammatory effects after resveratrol supplementation in overweight and obese individuals.
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4.
Placebo-controlled, randomised clinical trial: high-dose resveratrol treatment for non-alcoholic fatty liver disease.
Heebøll, S, Kreuzfeldt, M, Hamilton-Dutoit, S, Kjær Poulsen, M, Stødkilde-Jørgensen, H, Møller, HJ, Jessen, N, Thorsen, K, Kristina Hellberg, Y, Bønløkke Pedersen, S, et al
Scandinavian journal of gastroenterology. 2016;(4):456-64
Abstract
OBJECTIVE "The obesity epidemic" has led to an increase in obesity-related conditions including non-alcoholic fatty liver disease (NAFLD), for which effective treatments are in demand. The polyphenol resveratrol prevents the development of experimental NAFLD through modulation of cellular pathways involved in calorie restriction. We aimed to test the hypothesis that resveratrol alleviates NAFLD in a randomised, clinical trial. MATERIALS AND METHODS A total of 28 overweight patients with transaminasemia and histological NAFLD were randomised 1:1 to placebo or resveratrol 1.5 g daily for 6 months. Twenty-six participants completed the trial and underwent repeated clinical investigation, blood work, MR spectroscopy; and 19 participants agreed to a repeat liver biopsy. RESULTS Resveratrol treatment was generally not superior to placebo in improving plasma markers of liver injury (primary outcome: alanine transaminase, p = 0.51). Resveratrol-treated patients showed a 3.8% decrease in liver lipid content (p = 0.03), with no difference between the two treatment arms (p = 0.38) and no improvement of histological features. Resveratrol treatment was not associated with improvements in insulin sensitivity or markers of the metabolic syndrome, except for a transient decrease in systolic BP. Microarray analysis and qRT-PCR revealed no major changes in expression profile. Also, we report a serious adverse event in a patient who developed fever and bicytopenia. CONCLUSIONS In this placebo-controlled, high-dose and long-term study, resveratrol treatment had no consistent therapeutic effect in alleviating clinical or histological NAFLD, though there may be a small ameliorating effect on liver function tests and liver fat accumulation.
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5.
Beneficial action of resveratrol: How and why?
Diaz-Gerevini, GT, Repossi, G, Dain, A, Tarres, MC, Das, UN, Eynard, AR
Nutrition (Burbank, Los Angeles County, Calif.). 2016;(2):174-8
Abstract
Flavonoid resveratrol modulates the transcription factor NF-κB; inhibits the cytochrome P450 isoenzyme CYP1 A1; suppresses the expression and activity of cyclooxygenase enzymes; and modulates Fas/Fas-ligand-mediated apoptosis, p53, mammalian target of rapamycin, and cyclins and various phosphodiesterases. This increases the cytosolic cAMP that activates Epac1/CaMKKβ/AMPK/SIRT1/PGC-1α pathway, which in turn facilitates increased oxidation of fatty acids, mitochondrial biogenesis, mitochondrial respiration, and gluconeogenesis. Resveratrol triggers apoptosis of activated T cells and suppresses tumor necrosis factor-α, interluekin-17 (IL-17), and other proinflammatory molecules, and thus is of benefit in autoimmune diseases. In addition, resveratrol inhibits expression of hypoxia-inducible factor-1α and vascular endothelial growth factor, explaining its effective action against cancer. Brain-derived neurotrophic factor (BDNF) that is involved in the pathogenesis of obesity, type 2 diabetes mellitus, and metabolic syndrome is also altered in depression, schizophrenia, bipolar disorder, and autism. We noted that BDNF protects against cytotoxic actions of alloxan, streptozotocin, and benzo(a)pyrene. Resveratrol prevents bisphenol A-induced autism, type 2 diabetes mellitus, and metabolic syndrome, suggesting that it may augment BDNF synthesis and action. We also observed that BDNF levels are low in type 2 diabetes mellitus and that BDNF enhances production of antiinflammatory lipid, lipoxin A4, whose levels are low in diabetes mellitus. Thus, resveratrol may augment production of lipoxin A4. Resveratrol alters gut microbiota and influences stem cell proliferation and differentiation. These pleiotropic actions of resveratrol may explain the multitude of its actions and benefits.
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6.
Effect of resveratrol administration on metabolic syndrome, insulin sensitivity, and insulin secretion.
Méndez-del Villar, M, González-Ortiz, M, Martínez-Abundis, E, Pérez-Rubio, KG, Lizárraga-Valdez, R
Metabolic syndrome and related disorders. 2014;(10):497-501
Abstract
AIM: This study evaluated the effect of resveratrol administration on metabolic syndrome, insulin sensitivity, and insulin secretion. METHODS A randomized, double-blind, placebo-controlled clinical trial was carried out in 24 patients with diagnosis of metabolic syndrome in accordance with the International Diabetes Federation criteria. Glucose and insulin levels were measured after a 75-gram dextrose load. Triglycerides and high-density lipoprotein cholesterol concentrations at baseline were also evaluated. Twelve patients received trans-resveratrol (500 mg) three times per day before meals for 90 days. The remaining 12 patients received placebo at the same dose. The area under the curve (AUC) values of glucose and insulin, total insulin secretion, first-phase of insulin secretion, and insulin sensitivity were calculated. RESULTS After resveratrol administration, there were significant differences in total weight (94.4±13.2 vs. 90.5±12.3 kg, P=0.007), body mass index (BMI) (35.6±3.2 vs. 34.3±3.0 kg/m(2), P=0.006), fat mass (41.2±7.9 vs. 38.8±6.0 kg, P=0.001), and waist circumference (WC) (109±9 vs. 105±10 cm, P=0.004). There were also significant differences in AUC of insulin (48,418±22,707 vs. 26,473±8,273 pmol/L, P=0.003) and insulinogenic index (0.48±0.22 vs. 0.28±0.08, P=0.004). CONCLUSIONS Administration of resveratrol significantly decreases weight, BMI, fat mass, WC, AUC of insulin, and total insulin secretion.