Trans-resveratrol Supplementation Research Articles

Trans-resveratrol reduced hepatic oxidative stress in an animal model without inducing an upregulation of nuclear factor erythroid 2-related factor 2.

Trans-resveratrol, a widely used supplement for humans, aims to enhance the body's antioxidant defense. Studies suggest that it exerts anti-inflammatory and antioxidant effects by activating the nuclear factor erythroid 2-related factor 2 (Nrf2). In order to evaluate this hypothesis, LDLr(-/-) mice were fed a Western diet to induce liver inflammation and oxidative stress. One group was fed a diet containing 0.60 mg/day of trans-resveratrol (RESV), while another group received no dietary supplementation (CONT). Oxidative stress biomarkers and inflammatory cytokines were assessed in liver homogenates. It was observed that trans-resveratrol decreased hepatic oxidative stress by increasing the GSH/GSSG ratio and reducing malondialdehyde (MDA) concentration. However, the RESV group exhibited a reduction in Nrf2 relative expression compared to CONT. Additionally, trans-resveratrol supplementation reduced nuclear factor-κB (NF-κB) expression but led to an increase in IL-6, with no significant changes observed in tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) concentrations. Overall, these findings indicate that the in vivo antioxidant impact induced by trans-resveratrol supplementation in hepatic tissue did not correlate with increase of inflammatory cytokines and Nrf2 relative expression. Further exploration of alternative mechanisms, such as direct radical scavenger activity, is warranted to elucidate the antioxidant effect.

Can Resveratrol Supplementation Reduce Uremic Toxin Plasma Levels From the Gut Microbiota in Nondialyzed Patients With Chronic Kidney Disease?

Uremic toxins such as indoxyl sulfate (IS), p-cresyl sulfate (pCS), and indole-3-acetic acid (IAA) produced by the gut microbiota are recognized as risk factors for many comorbidities, including cardiovascular diseases. Patients with chronic kidney disease (CKD) have an accumulation of these toxins, and nutritional strategies have been proposed to mitigate gut dysbiosis and, consequently, reduce these toxins. This study aimed to evaluate the effects of resveratrol supplementation on the plasma levels of IS, pCS, and IAA in nondialyzed patients with CKD. In this placebo-controlled crossover study, twenty nondialyzed patients were randomly divided into two groups: they received either one capsule/day containing 500mg of trans-resveratrol (63±7.5years, glomerular filtration rate [GFR]: 34±14mL/min, body mass index: 26.8±5.6kg/m2) or a placebo containing 500mg wheat flour (62±8.4years, GFR: 34±13mL/min, body mass index: 28.6±4.4kg/m2) during 4weeks. After 8weeks of washout (no supplementation), another 4weeks of supplementation with crossover was initiated. IS, IAA, and pCS plasma levels were quantified by the reverse phase high-efficiency liquid chromatography method with fluorescent detection. The mRNA expression of nuclear factor erythroid 2-related factor 2 and nuclear factor kappa B in peripheral blood mononuclear cells was evaluated by polymerase chain reaction. C-reactive protein plasma levels were also evaluated. As expected, the uremic toxin levels were negatively correlated with the GFR, but no effect of trans-resveratrol supplementation was found on levels of IS, IAA, and pCS. There was a positive correlation between IS and nuclear factor erythroid 2-related factor 2 (r=0.24, P=.03) and also between IS and C-reactive protein (r=0.21, P=.05). Supplementation with trans-resveratrol did not reduce the plasma levels of IS, pCS, and IAA in nondialyzed patients with CKD. The interactions among uremic toxins and anti-inflammatory and proinflammatory pathways deserve more studies.

SIRT1-dependent effects of resveratrol and grape juice in an in vitro model of preeclampsia

Preeclampsia (PE) is a multifactorial hypertensive disorder of pregnancy that is partly responsible for both maternal and fetal morbidity and mortality levels worldwide. It has been recently discovered that sirtuin-1 (SIRT1) is reduced in the circulation and in an in vitro model of PE. Therefore, in this study, we investigated the effects of trans-resveratrol, a potent antioxidant and activator of SIRT1, on oxidative stress and nitric oxide (NO) production in an in vitro model of PE compared to gestational hypertensive (GH) and healthy pregnant (HP) women. Furthermore, we also evaluated the effects of an acute intake of grape juice on women with PE to assess whether it could mimic in vitro trans-resveratrol supplementation.(1) In the GH group, resveratrol decreased intracellular reactive oxygen species (ROS) and increased their antioxidant capacity, while inhibiting SIRT1 reestablished previous levels. (2) In PE, inhibition of SIRT1 increased antioxidant activity. (3) Intracellular NO and supernatant nitrite levels were increased by inhibiting SIRT1 in the PE group. (4) Grape juice intake increased intracellular NO levels versus before grape juice intake control; however, the inhibition of SIRT1 before grape juice intake initially increased NO, but decreased it 1 h after grape juice intake.In conclusion, activating SIRT1 by using resveratrol alone may not be beneficial to women with PE, and GH and PE seem to have different responsive mechanisms to this molecule. Furthermore, grape juice intake seems to have different effects compared to resveratrol supplementation alone in this in vitro model of PE, demonstrating the potential of the combination of other biologically active molecules from grape juice over the SIRT1-eNOS-NO in PE treatment.

The Impact of Resveratrol Supplementation on Inflammation Induced by Acute Exercise in Rats: Il6 Responses to Exercise.

Severe physical activity leads to a sharp increase in free radicals, an oxidative stress, inflammation, and tissue damage. Resveratrol as one of the antioxidants can be effective in preventing the effects of oxidative stress. Therefore, the present study was aimed to evaluate the effect of trans-resveratrol supplementation and training exercise on inflammation-related factors. Sixty-four male Wistar rats were divided into six groups, each group consisting of 16 animals: 1) excursive + trans-resveratrol, 2) exercise group, 3) trans-resveratrol group, and 4) control group. Following the familiarization sessions, a more consistent protocol with an intensity of 65% vo2 max was performed for 12 weeks. Afterward, half of the mice in each group received acute exercise training with an intensity of 70-75% of vo2 max at the age of 20 weeks, until reaching the disability level. Finally, the levels of inflammatory markers were measured using special kits. Our findings depicted that inflammatory factors such as CPR, TNF-α, IL-6, and IL-7 were not affected by endurance protocol (P > 0.05), whereas, they were significantly increased by acute exercise training (P > 0.05). Additionally, we found that RES supplements led to a decrease in CPR and IL-6 levels, while not affecting TNF-α and IL-17 levels. According to available evidence, RES appears to have anti-inflammatory and protective effects during exercise by reducing inflammatory factors. Further studies are required to clarify the role of trans-resveratrol supplementation after exercise training.

Effects of trans-resveratrol on type 1 diabetes-induced inhibition of retinoic acid metabolism pathway in retinal pigment epithelium of Dark Agouti rats

Genesis and progression of diabetic retinopathy are due to glucotoxicity-induced changes in intracellular milieu in the retina. This study investigated effects of trans-resveratrol on type 1 diabetes-induced changes in gene expressions and retinoic acid metabolism pathway in the RPE (retinal pigment epithelium) of Dark Agouti rats. Microarray analysis showed differential expressions of 833 genes in the RPE of 14 day-long diabetic rats, which increased to 1249 after they received 5 mg/kg trans-resveratrol. Diabetes inhibited the expression of retinoic acid metabolism pathway genes- Lpl, Lrat, RPE65, Rdh5, Rdh10, Rdh12, Rlbp1 and Rbp1 and increased Crabp1. Trans-resveratrol further downregulated the expression of these genes except Lpl, Rdh5, and Rdh12 but upregulated Cyp26b1. RT-PCR showed inhibition of Lrat, Rdh5, and Rdh10 in diabetic rats supplemented with or without trans-resveratrol on 14d. Trans-resveratrol normalized Rdh5 and increased Lrat and Rdh10 transcriptions compared to control and diabetic rats. Trans-resveratrol amplified diabetes-induced inhibition of RPE65, but it inhibited the induced increase in Crabp1 transcription on 30d. Trans-resveratrol reversed the diabetes-induced decrease in Cyp26b1 transcription on 14d and 30d and normalized Cyp3a9 transcription on 30d. Trans-resveratrol normalized the diabetes-induced increase in Rdh5, Rdh10, and Cyp3a9 protein levels, but it further increased Cyp26b1 protein level. In conclusion, diabetes differentially regulates numerous genes in the RPE, including that of retinoic acid metabolism pathway. Trans-resveratrol supplementation is beneficial to normalize long-term effects, but not short-term effects, of diabetes on retinoic acid metabolism pathway in the RPE.

Cerebral Blood Flow Measurements in Adults: A Review on the Effects of Dietary Factors and Exercise.

Improving cerebrovascular function may be a key mechanism whereby a healthy lifestyle, of which a healthy diet combined with increased physical activity levels is a cornerstone, protects against cognitive impairments. In this respect, effects on cerebral blood flow (CBF)—a sensitive physiological marker of cerebrovascular function—are of major interest. This review summarizes the impact of specific dietary determinants and physical exercise on CBF in adults and discusses the relation between these effects with potential changes in cognitive function. A limited number of randomized controlled trials have already demonstrated the beneficial effects of an acute intake of nitrate and polyphenols on CBF, but evidence for a relationship between these effects as well as improvements in cognitive functioning is limited. Moreover, long-term trans-resveratrol supplementation has been shown to increase CBF in populations at increased risk of accelerated cognitive decline. Long-term supplementation of n-3 long-chain polyunsaturated fatty acids may also increase CBF, but related effects on cognitive performance have not yet been found. Significant decreases in cerebral perfusion were observed by commonly consumed amounts of caffeine, while alcohol intake was shown to increase CBF in a dose-dependent way. However, the long-term effects are not clear. Finally, long-term exercise training may be a promising approach to improve CBF, as increases in perfusion may contribute to the beneficial effects on cognitive functioning observed following increased physical activity levels.

Beneficial effects of acute trans-resveratrol supplementation in treated hypertensive patients with endothelial dysfunction

ABSTRACTEndothelial dysfunction is a surrogate marker of cardiovascular risk. Resveratrol is known to improve endothelial function in animals, however, clinical trials are limited. We hypothesized that the acute trans-resveratrol supplementation improves endothelial function in treated hypertensive patients with endothelial dysfunction. Twenty-four hypertensive patients between 45 and 65 years-old with baseline endothelial dysfunction were enrolled in a randomized, cross-over, double-blind, placebo-controlled trial. Individuals received either a single dose of trans-resveratrol (300 mg) or placebo and were crossed-over after a one-week washout period. Blood pressure (BP) measurements, aortic systolic blood pressure (SBP) and brachial flow-mediated dilation (FMD) were performed before and 1.5 hours after the intervention. FMD was significantly increased in women (4.2 ± 0.5 vs 7.1 ± 1.3%, p = 0.026) but not in men (4.4 ± 0.9 vs 4.9 ± 0.8%, p = 0.588) in the trans-resveratrol group. There was no statistical difference between baseline and final values of brachial BP and also no changes in aortic SBP. Patients with higher low-density lipoprotein (LDL) cholesterol had better FMD response to trans-resveratrol than patients with lower LDL cholesterol (7.4 ± 1.2 vs 4.3 ± 1.0%, p = 0.004). Our study demonstrated that the acute supplementation of trans-resveratrol promoted an improvement in endothelial function, especially in women and those with higher LDL-cholesterol, despite no changes in BP.List of Abbreviation: Aix: augmentation index; AP: augmentation pressure; BP: blood pressure; BMI: body Mass Index; CVD: cardiovascular disease; FMD: flow-mediated dilation; FRS: Framingham Risk Score; HDL: high-density lipoprotein; LDL: low-density lipoprotein; NO: nitric oxide; SPSS: Statistical Package for Social Sciences; ROS: reactive oxygen species; SBP: systolic blood pressure; TG: triglycerides.

Trans-Resveratrol Supplementation and Endothelial Function during the Fasting and Postprandial Phase: A Randomized Placebo-Controlled Trial in Overweight and Slightly Obese Participants.

Studies on the effects of the long-term intake of trans-resveratrol on vascular function are conflicting. In addition, postprandial effects of long-term trans-resveratrol intake on endothelial function are not known. We therefore supplemented 45 overweight and slightly obese volunteers (25 men and 20 women) with a mean (±SD) age of 61 ± 7 years and body mass index of 28.3 ± 3.2 kg/m2 in random order trans-resveratrol (2 × 75 mg/day) or placebo capsules for 4 weeks, separated by a washout period of at least 4 weeks. At the end of each intervention period, brachial artery flow-mediated vasodilation (FMD) was measured before and after meal consumption. Plasma biomarkers for endothelial function, inflammation, and glucose and lipid metabolism were also determined. Compared with the placebo, trans-resveratrol did not affect fasting FMD (2.9 ± 1.4% vs. 3.0 ± 1.9%; p = 0.69). After the postprandial test, changes in FMD (−0.7 ± 2.3% vs. 0.2 ± 2.6%; p = 0.13) were also not significantly different. Postprandial changes in biomarkers were also comparable. In conclusion, for overweight and slightly obese volunteers, a daily intake of 150 mg of trans-resveratrol for 4 weeks does not change plasma biomarkers of endothelial function or inflammation in the fasting state or postprandial phase.

<b>Trans-resveratrol reduces cardiac oxidative stress in rats exposed to cigarette smoke

Differences between reactive oxygen species and antioxidant defense system unbalance the redox status. The exposure to cigarette smoke can increase this imbalance. Trans-resveratrol is a polyphenol with great antioxidant action that reduces the oxidative stress. This study investigated the effect of the trans-resveratrol supplementation on the cardiac oxidative stress in rats exposed to cigarette smoke. Male Wistar rats were randomized into four groups: Control Group (CG), Exposure to Smoke Group (ESG), Antioxidant Group (AG) and Exposure to Smoke plus Antioxidant Group (ESAG). Animals were exposed to cigarette smoke and supplemented with trans-resveratrol (6.0 mg kg -1 ) for two months. The lipid peroxidation (TBARS) and the enzymatic activity of catalase (CAT) were measured in the cardiac muscle. The ESG presented the highest lipid peroxidation level compared with CG (p < 0.001), AG (p < 0.001) and ESAG (p < 0.006). The CAT activity was higher in the AG (p < 0.001) and ESAG (p < 0.001) compared with CG. The ESG presented lower CAT activity compared with the ESAG (p < 0.001). The supplementation of Trans-resveratrol attenuated the cardiac oxidative stress and increased the activity of catalase. Our findings evidenced the cardioprotective effect of trans-resveratrol in rats exposed to cigarette smoke.

Assessment of the effect of prolonged forced swimming on CD-1 mice sperm morphology with and without antioxidant supplementation

As physical exercise has been shown to negatively affect sperm morphology, this study was undertaken to assess the effect of a 3-min forced swimming protocol during 50 days, with and without administration of antioxidants [N-acetylcysteine (NAC) and trans-resveratrol], on sperm morphology in CD-1 mice. Forty-four 13-week-old CD-1 mice were randomly allocated to four different groups: mice not submitted to exercise, control group (CG), mice submitted to swimming without administration of antioxidants (EX), mice submitted to swimming that received trans-resveratrol supplementation [exercise group (EX)+Resv] and mice submitted to swimming exercise that received NAC supplementation (EX+NAC). The EX showed 30.5% of spermatozoa with normal morphology, showing significant differences with regard to the CG, which showed 58.5%. The groups receiving antioxidant supplements showed significantly higher percentages of spermatozoa with normal morphology in comparison with the EX group (EX+Resv: 64.1%, EX+NAC: 48.2%). The imposed model of forced swimming caused alterations in sperm morphology. The antioxidants employed seem to be suitable antioxidants for avoiding exercise-associated sperm morphology anomalies in prolonged forced swimming exercise. Trans-resveratrol has proven to be more efficient for this purpose.

Reshaping faecal gut microbiota composition by the intake of trans-resveratrol and quercetin in high-fat sucrose diet-fed rats

Diet-induced obesity is associated to an imbalance in the normal gut microbiota composition. Resveratrol and quercetin, widely known for their health beneficial properties, have low bioavailability, and when they reach the colon, they are targets of the gut microbial ecosystem. Hence, the use of these molecules in obesity might be considered as a potential strategy to modulate intestinal bacterial composition. The purpose of this study was to determine whether trans-resveratrol and quercetin administration could counteract gut microbiota dysbiosis produced by high-fat sucrose diet (HFS) and, in turn, improve gut health. Wistar rats were randomised into four groups fed an HFS diet supplemented or not with trans-resveratrol [15 mg/kg body weight (BW)/day], quercetin (30 mg/kg BW/day) or a combination of both polyphenols at those doses. Administration of both polyphenols together prevented body weight gain and reduced serum insulin levels. Moreover, individual supplementation of trans-resveratrol and quercetin effectively reduced serum insulin levels and insulin resistance. Quercetin supplementation generated a great impact on gut microbiota composition at different taxonomic levels, attenuating Firmicutes/Bacteroidetes ratio and inhibiting the growth of bacterial species previously associated to diet-induced obesity (Erysipelotrichaceae, Bacillus, Eubacterium cylindroides). Overall, the administration of quercetin was found to be effective in lessening HFS-diet-induced gut microbiota dysbiosis. In contrast, trans-resveratrol supplementation alone or in combination with quercetin scarcely modified the profile of gut bacteria but acted at the intestinal level, altering the mRNA expression of tight-junction proteins and inflammation-associated genes.

Resveratrol as a supplement to exercise training: friend or foe?

Resveratrol as a supplement to exercise training: friend or foe?

Effects of trans-resveratrol supplementation on pAMPK in response to an oral glucose tolerance test and graded exercise test in overweight females

Effects of trans-resveratrol supplementation on pAMPK in response to an oral glucose tolerance test and graded exercise test in overweight females