The effects of resveratrol on lipid profiles and liver enzymes in patients with metabolic syndrome and related disorders: a systematic review and meta-analysis of randomized controlled trials

Akbari, Maryam; Tamtaji, Omid Reza; Lankarani, Kamran Bagheri; Tabrizi, Reza; Dadgostar, Ehsan; Haghighat, Neda; Kolahdooz, Fariba; Ghaderi, Amir; Mansournia, Mohammad Alì; Asemi, Zatollah

doi:10.1186/s12944-020-1198-x

Cited by 38 publications

(29 citation statements)

References 60 publications

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“…Although some studies did not show any improvement in the glucose intolerance in older adults [138] and type 2 diabetic patients [139,140], however, RSV has a positive impact on blood pressure [141,142], improves insulin sensitivity [143], and reduces blood glucose levels [144] in type 2 diabetic patients and patients with non-alcoholic fatty liver disease [145], in the treatment of pre-eclampsia [146] and obese people [97]. Consistently, most recent meta analysis also indicates that RSV improves cardiometabolic health by decreasing some risk factors (HOMA-IR, LDL-C, and T-Chol) associated with cardiovascular disease (CVD) [147,148] and significantly reduced total cholesterol and increased gammaglutamyl transferase (GGT) concentrations in patients with metabolic syndrome (MetS) and related disorders [149]. In conclusion, along with substantial protective/ beneficial effects of low-dose RSV demonstrated in various studies, exacerbation of the disease conditions especially by higher doses of RSV is also an accompanying theme in human clinical trials.…”

Section: Rsv Elicits Favorable and Unexpected Outcomes In Human Clinimentioning

confidence: 83%

Towards resolving the enigma of the dichotomy of resveratrol: cis- and trans-resveratrol have opposite effects on TyrRS-regulated PARP1 activation

2020

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Unlike widely perceived, resveratrol (RSV) decreased the average lifespan and extended only the replicative lifespan in yeast. Similarly, although not widely discussed, RSV is also known to evoke neurite degeneration, kidney toxicity, atherosclerosis, premature senescence, and genotoxicity through yet unknown mechanisms. Nevertheless, in vivo animal models of diseases and human clinical trials demonstrate inconsistent protective and beneficial effects. Therefore, the mechanism of action of RSV that elicits beneficial effects remains an enigma. In a previously published work, we demonstrated structural similarities between RSV and tyrosine amino acid. RSV acts as a tyrosine antagonist and competes with it to bind to human tyrosyl-tRNA synthetase (TyrRS). Interestingly, although both isomers of RSV bind to TyrRS, only the cis-isomer evokes a unique structural change at the active site to promote its interaction with poly-ADPribose polymerase 1 (PARP1), a major determinant of cellular NAD +-dependent stress response. However, retention of trans-RSV in the active site of TyrRS mimics its tyrosine-bound conformation that inhibits the autopoly-ADP-ribos(PAR)ylation of PARP1. Therefore, we proposed that cis-RSV-induced TyrRS-regulated auto-PARylation of PARP1 would contribute, at least in part, to the reported health benefits of RSV through the induction of protective stress response. This observation suggested that trans-RSV would inhibit TyrRS/PARP1mediated protective stress response and would instead elicit an opposite effect compared to cis-RSV. Interestingly, most recent studies also confirmed the conversion of trans-RSV and its metabolites to cis-RSV in the physiological context. Therefore, the finding that cis-RSV and trans-RSV induce two distinct conformations of TyrRS with opposite effects on the auto-PARylation of PARP1 provides a potential molecular basis for the observed dichotomic effects of RSV under different experimental paradigms. However, the fact that natural RSV exists as a diastereomeric mixture of its cis and trans isomers and cis-RSV is also a physiologically relevant isoform has not yet gained much scientific attention. Keywords Resveratrol (RSV). Aminoacyl-tRNA synthetases (aaRSs). Tyrosyl-tRNA synthetase (YARS. TyrRS). Nicotinamide adenine nucleotide (NAD +). Poly-ADP-ribose polymerase (PARP). Sirtuins (SIRT). AMP-activated protein kinase (AMPK). Nicotinamide (NAM) GeroScience

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Section: Rsv Elicits Favorable and Unexpected Outcomes In Human Clinimentioning

confidence: 83%

Towards resolving the enigma of the dichotomy of resveratrol: cis- and trans-resveratrol have opposite effects on TyrRS-regulated PARP1 activation

2020

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“…Unfortunately, a randomized, double-blind, and placebo-controlled clinical trial in overweight and insulin-resistant patients who received resveratrol at a dose of 75–150 mg/day for 12 weeks showed no effect on Liver fat content [ 165 ]. A recent meta-analysis of randomized controlled trials in patients with metabolic syndrome showed that resveratrol significantly reduced not only the total cholesterol levels, but also increased GGT, with an overall potential cardioprotective effect [ 187 ].…”

Section: Liver Disease and Resveratrol: Clinical Trialsmentioning

confidence: 99%

The Role of Resveratrol in Liver Disease: A Comprehensive Review from In Vitro to Clinical Trials

et al. 2021

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Many studies have shown that resveratrol has a lot of therapeutic effects on liver disorders. Its administration can significantly increase the survival rate after liver transplantation, reduce fat deposition and ischemia-induced necrosis and apoptosis in Wistar rats. Resveratrol can provide Liver protection against chemical, cholestatic, and alcohol-mediated damage. It can improve glucose metabolism and lipid profile, reduce liver fibrosis, and steatosis. Additionally, it is capable of altering the fatty acid composition of the liver cells. Resveratrol may be a potential treatment option for the management of non-alcoholic fatty liver disease (NAFLD) due to its anti-inflammatory, antioxidant, and calorie-restricting effects. There are also studies that have evaluated the effect of resveratrol on lipid and liver enzyme profiles among patients with metabolic syndrome (MetS) and related disorders. Based on the extent of liver disease worldwide and the need to find new treatment possibilities, this review critically examines current in vitro and in vivo preclinical studies and human clinical studies related to liver protection.

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“…The authors conclude that resveratrol regulates the expression of PPARγ, responsible of the lipid metabolism [234]. Analyzing the most recent clinical trials, resveratrol appears to reduce plasma concentrations of total cholesterol and TG [235] but it does not affect HDL-C and LDL-C concentrations [242].…”

Section: Lipid Profilementioning

confidence: 99%

Natural Bioactive Compounds Useful in Clinical Management of Metabolic Syndrome

et al. 2021

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Metabolic syndrome (MetS) is a clinical manifestation characterized by a plethora of comorbidities, including hyperglycemia, abdominal obesity, arterial hypertension, and dyslipidemia. All MetS comorbidities participate to induce a low-grade inflammation state and oxidative stress, typical of this syndrome. MetS is related to an increased risk of cardiovascular diseases and early death, with an important impact on health-care costs. For its clinic management a poly-pharmaceutical therapy is often required, but this can cause side effects and reduce the patient’s compliance. For this reason, finding a valid and alternative therapeutic strategy, natural and free of side effects, could represent a useful tool in the fight the MetS. In this context, the use of functional foods, and the assumption of natural bioactive compounds (NBCs), could exert beneficial effects on body weight, blood pressure and glucose metabolism control, on endothelial damage, on the improvement of lipid profile, on the inflammatory state, and on oxidative stress. This review focuses on the possible beneficial role of NBCs in the prevention and in the clinical management of MetS and its comorbidities.

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The effects of resveratrol on lipid profiles and liver enzymes in patients with metabolic syndrome and related disorders: a systematic review and meta-analysis of randomized controlled trials

Cited by 38 publications

References 60 publications

Towards resolving the enigma of the dichotomy of resveratrol: cis- and trans-resveratrol have opposite effects on TyrRS-regulated PARP1 activation

Towards resolving the enigma of the dichotomy of resveratrol: cis- and trans-resveratrol have opposite effects on TyrRS-regulated PARP1 activation

The Role of Resveratrol in Liver Disease: A Comprehensive Review from In Vitro to Clinical Trials

Natural Bioactive Compounds Useful in Clinical Management of Metabolic Syndrome

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