Resveratrol Attenuates the Expression of HMG-CoA Reductase mRNA in Hamsters. EGCG (epigallocatechin-3-gallate) + RSV (282 and 80 mg/d, respectively) or placebo for 12 wk. Plin C., Tillement J.P., Berdeaux A., Morin D. Resveratrol Protects against Cold Ischemia-warm Reoxygenation-induced Damages to Mitochondria and Cells in Rat Liver. Yonamine C.Y., Pinheiro-Machado E., Michalani M.L., Alves-Wagner A.B., Esteves J.V., Freitas H.S., Machado U.F. Bhardwaj A., Sethi G., Vadhan-Raj S., Bueso-Ramos C., Takada Y., Gaur U., Nair A.S., Shishodia S., Aggarwal B.B. Moreover, RSV increased the antioxidant capacity of plasma with a consequent reduction in oxidative stress markers involved in DNA damage [189]. Lu M.C., Ji J.A., Jiang Z.Y., You Q.D. Larson A.M., Polson J., Fontana R.J., Davern T.J., Lalani E., Hynan L.S., Reisch J.S., Schidt F.V., Ostapowicz G., Shakil A.O., et al. National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database. The Protective Effect of Resveratrol on Dimethylnitrosamine-induced Liver Fibrosis in Rats. Effects of resveratrol supplementation on liver enzymes: A - PubMed Resveratrol Inhibits Nonalcoholic Fatty Liver Disease in Rats. Diagnosis and Management of Non-alcoholic Fatty Liver Disease. Resveratrol can provide Liver protection against chemical, cholestatic, and alcohol-mediated damage. Meza-Torres C., Hernndez-Camacho J.D., Corts-Rodrguez A.B., Fang L., Bui Thanh T., Rodrguez-Bies E., Navas P., Lpez-Lluch G. Resveratrol Regulates the Expression of Genes Involved in CoQ Synthesis in Liver in Mice Fed with High Fat Diet. The mechanisms underlying the beneficial effects of resveratrol have not been fully elucidated and have mainly been related to its antioxidant activity [8]. Mikolasevic I., Filipec-Kanizaj T., Mijic M., Jakopcic I., Milic S., Hrstic I., Sobocan N., Stimac D., Burra P. Nonalcoholic Fatty Liver Disease and Liver TransplantationWhere Do We Stand? Excess iron in the liver can lead to many adverse effects, such as damage from oxidative stress and inflammation, fibrosis, and liver damage. Resveratrol offered protection and prevented oxidative stress and inflammation associated with ischemia-reperfusion in rats [152]. Knop F.K., Konings E., Timmers S., Schrauwen P., Holst J.J., Blaak E.E. [102] examined the effect of resveratrol on CCI4-induced hepatotoxicity (carbon tetrachloride). Resveratrol: MedlinePlus Supplements [132,133]. The Role of Resveratrol in Cancer Therapy. This study, although conducted using a large sample size did not take into consideration the importance of the dose-dependent effect of resveratrol due to its low bioavailability [166]. Asghari S., Rafraf M., Farzin L., Asghari-Jafarabadi M., Ghavami S.M., Somi M.H. 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. RSV also increases hexokinase and pyruvate kinase activity and decreases the activity of lactate dehydrogenase and glucose-6-phosphatase [99]. Red arrow () indicates down-regulation; white arrow () indicates up-regulation. Carrizzo A., Forte M., Damato A., Trimarco V., Salzano F., Bartolo M., Maciag A., Puca A.A., Vecchione C. Antioxidant Effects of Resveratrol in Cardiovascular, Cerebral and Metabolic Diseases. Xin P., Han H., Gao D., Cui W., Yang X., Ying C., Sun X., Hao L. Alleviative Effects of Resveratrol on Nonalcoholic Fatty Liver Disease are Associated with up Regulation of Hepatic Low Density Lipoprotein Receptor and Scavenger Receptor Class B Type I Gene Expressions in Rats. It also increased hepatic Nrf2 and reduced iNOS (inducible nitric oxide synthase) expression. Yang T., Li S., Zhang X., Pang X., Lin Q., Cao J. Resveratrol, Sirtuins, and Viruses. Possible Protective Effects of Resveratrol in Hepatocellular Carcinoma. Non-alcoholic fatty liver disease (NAFLD) affects up to 30% of adults in Western countries and at least 15% in Asian countries. Resveratrol Improves Glycemic Control in Type 2 Diabetic Obese Mice by Regulating Glucose Transporter Expression in Skeletal Muscle and Liver. Almeida L., Vaz-da-Silva M., Falco A., Soares E., Costa R., Loureiro A.I., Fernandes-Lopes C., Rocha J.F., Nunes T., Wright L., et al. However, studies so far have not found specific doses and administration intervals for this compound. Dash S., Xiao C., Morgantini C., Szeto L., Lewis G.F. High-dose Resveratrol Treatment for 2 Weeks Inhibits Intestinal and Hepatic Lipoprotein Production in Overweight/Obese Men. Summary results of the clinical trials of Resveratrol in different models. RESVERATROL - Uses, Side Effects, and More - WebMD Nakamura et al. A few recent studies have shown the hepatoprotective effects of resveratrol in the high fat diet . Zhu L., Mou Q., Wang Y., Zhu Z., Cheng M. Resveratrol Contributes to the Inhibition of Liver Fibrosis by Inducing Autophagy via the microRNA-20a-mediated Activation of the PTEN/PI3K/AKT Signaling Pathway. a member of Resveratrol prevents liver damage in MCD . Trans-Resveratrol has been used in the form of micronized formulation, which is better absorbed, has strong antioxidants effects, is more effective than plain resveratrol . Apoptosis Control by Death and Decoy Receptors. Additionally, this effect was obtained at a dose of 50 mg/kg/day for 14 days in a model of chemically induced acute liver injury [105]. Effect of resveratrol on non-alcoholic fatty liver disease In fact, RSV administration reduces portal pressures, the activation of hepatic stellate cells, and improves hepatic endothelial functioning in cirrhotic rats, with an overall positive effect on cirrhosis and portal hypertension [47,48,49]. Reduction in DENA-induced lipid peroxidation, iNOS; Restoring of cellular antioxidant defenses, Blocking of VEGFR expression through HIF-1a downregulation, RSV dissolved in DMSO at a concentration of 25 mM, Reduction in cyclin D1, p38 MAP kinase, Akt, and Pak1 expression. Chambers K.F., Day P.E., Aboufarrag H.T., Kroon P.A. Resveratrol, an antioxidant and anti-inflammatory natural plant polyphenol, is widely used in agriculture for the prevention of oxidative stress-related diseases. All of these effects determine a shift in the metabolic pathways towards reduced hepatic glucose production. Calvo-Castro L.A., Schiborr C., David F., Ehrt H., Voggel J., Sus N., Behnam D., Bosy-Westphal A., Frank J. Ding L., Zhang B., Li J., Yang L., Wang Z. Effects of Pharmacologic Dose of Resveratrol Supplementation on Oxidative/Antioxidative Status Biomarkers in Nonalcoholic Fatty Liver Disease Patients: A Randomized, Double-Blind, Placebo-Controlled Trial. This was highlighted by a reduction in TBARS (thiobarbituric acid reactive substances), AST, ALT, conjugated dienes, and bilirubin levels. Liver diseases remain a heavy health burden worldwide. Xu M., Xue W., Ma Z., Bai J., Wu S. Resveratrol Reduces the Incidence of Portal Vein System Thrombosis after Splenectomy in a Rat Fibrosis Model. Bethesda, MD 20894, Web Policies Hassan-Khabbar S., Vamy M., Cottart C.H., Wendum D., Vibert F., Savouret J.F., Thrond P., Clot J.P., Waligora A.J., Nivet-Antoine V. Protective Effect of Post-ischemic Treatment with Trans-resveratrol on Cytokine Production and Neutrophil Recruitment by Rat Liver. Acetaminophen Overdose. IL-6 mRNA expression, an anti-inflammatory marker, was higher in the livers of BALB/c mice than those of C57BL/6 mice 24 h after administration. Naphthalene-induced liver damage and resveratrol hepatoprotective pharmacological effects have been investigated in mice. Resveratrol (10 mg/kg) for 15 days in streptozotocin (STZ)-induced diabetic rats has shown hepatoprotective effects against diabetes-induced liver damage via reduction of serum glucose level and oxidative damage and improving serum lipid profile. [11] showed that resveratrol reduces the diet-induced accumulation of hepatic fat through increased oxidation of fatty acids and reductions in lipogenesis. Most J., Timmers S., Warnke I., Jocken J.W., van Boekschoten M., de Groot P., Bendik I., Schrauwen P., Goossens G.H., Blaak E.E. In conclusion, patients undergoing peritoneal dialysis in oral therapy with 450 mg of RSV delivered daily over 12 weeks, demonstrated improved urinary ultrafiltration and decreased vascular endothelial growth factor, fetal liver kinase-1, and angiopoietin- 2 (markers of angiogenesis) levels when ingested at the highest dose available [191]. Azachi M., Yatuv R., Katz A., Hagay Y., Danon A. Yu L., Sun Z.J., Wu S.L., Pan C.E. In a study involving 10 healthy subjects, the administration of a single dose of 5 g RSV showed a significant increase in tumour necrosis factor- (TNF-) in patients plasma after 24 h. This increased production of TNF-, as well as the inhibition of IL-10, was confirmed by analysis of peripheral blood mononuclear cells (PBMCs), which were activated through several toll receptor agonists [188]. Obesity is a major risk factor for non-alcoholic fatty liver disease [].Resveratrol possesses beneficial properties that are fundamental in preventing this metabolic condition, therefore attenuating liver inflammation [11,12,13,14].The effects of resveratrol on non-alcoholic fatty liver disease (NAFLD) are correlated to the regulation of Low-Density Lipoprotein (LDL) receptors []. Resveratrol Prevents Hepatic Steatosis Induced by Hepatitis C Virus Core Protein. These findings were associated with an increase in Ki67 (+) hepatocytes, thereby promoting their proliferation [55]. Therefore, the role of resveratrol in liver protection against chemical damage derives mainly from its ability to suppress oxidative stress and apoptosis. de Oliveira M.R., Chenet A.L., Duarte A.R., Scaini G., Quevedo J. Molecular Mechanisms Underlying the Anti-depressant Effects of Resveratrol: A Review. Numerous studies have shown that resveratrol can prevent or slow the progression of a wide variety of diseases, including malignant tumours, neurodegenerative diseases, cardiovascular disorders, ischemic lesions, and viral infections [2,3,4,5]. A Novel Promising Frontier for Human Health: The Beneficial Effects of Nutraceuticals in Cardiovascular Diseases. Effects of Resveratrol on Biomarkers of Oxidative Stress and on the Activity of Delta Aminolevulinic Acid Dehydratase in Liver and Kidney of Streptozotocin-induced Diabetic Rats. Yun H., Park S., Kim M.J., Yang W.K., Im D.U., Yang K.R., Hong J., Choe W., Kang I., Kim S.S., et al. Yu B., Qin S.Y., Hu B.L., Qin Q.Y., Jiang H.X., Luo W. Resveratrol Improves CCL4-induced Liver Fibrosis in Mouse by Upregulating Endogenous IL-10 to Reprogramme Macrophages Phenotype from M(LPS) to M(IL-4). Another study, involving the application of a model of cholestatic liver damage induced by ANIT (-naphthyl isothiocyanate), showed that resveratrol pre-treatment effectively attenuated ANIT-induced acute cholestasis and liver injury in rats [56,57]. Natural Polyphenols: Potential in the Prevention of Sexually Transmitted Viral Infections. Rotches-Ribalta M., Andres-Lacueva C., Estruch R., Escribano E., Urpi-Sarda M. Pharmacokinetics of Resveratrol Metabolic Profile in Healthy Humans after Moderate Consumption of Red Wine and Grape Extract Tablets. Mech. Abdu S.B., Al-Bogami F.M. It can improve glucose . Res. C.I. Upadhyay G., Singh A.K., Kumar A., Prakash O., Singh M.P. Fontana R.J. On the other hand, another analysis showed an interesting reduction in TNF- in NAFLD patients [169]. Otherwise, at doses of 2.5 g or more per day, side effects may occurs, like nausea, vomiting, diarrhea and liver dysfunction in patients with non-alcoholic fatty liver disease . Gracia A., Fernndez-Quintela A., Miranda J., Eseberri I., Gonzlez M., Portillo M.P. Kirimlioglu et al. Delmas D., Rb C., Lacour S., Filomenko R., Athias A., Gambert P., Cherkaoui-Malki M., Jannin B., Dubrez-Daloz L., Latruffe N., et al. 4 Nonalcoholic Fatty Liver Disease Treatments Resveratrol: A Multitargeted Agent for Age-associated Chronic Diseases. Although proven safe, RSV does not have optimal pharmacokinetics and pharmacodynamics properties [194,195,196]. Resveratrol Enhances TNF- Production in Human Monocytes upon Bacterial Stimulation. Resveratrol is a potent activator of both SIRT1 and AMPK [26]. The anti-proliferative activity of resveratrol is mainly linked to triggering apoptosis of tumour cells [59,60,61,62,63,64]. Rafiee S., Mohammadi H., Ghavami A., Sadeghi E., Safari Z., Askari G. Efficacy of Resveratrol Supplementation in Patients with Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis of Clinical Trials. Influence of Resveratrol on Liver Fibrosis Induced by Dimethylnitrosamine in Male Rats. A possible reason for the conflicting results could be that a low dose or a single high dose [188] has no positive effects on health and may even cause undesired effects. One of the hepatotoxic chemicals, cadmium, was investigated. Moreover, there was a dose-dependent effect, as the largest reduction was seen at a dose of 2.5 g. Therefore, the preventive chemo action of RSV in humans was shown to act through the IGF system, which serves as a biomarker [183]. Resveratrol also reduced the pyrogallol-induced increase in the activity of the metabolizing enzymes CYP1A2 (cytochrome P450 1A2) and CYP2E1 (cytochrome P450 2E1) [137]. Ylmaz Z., Kalaz E.B., Aydn A.F., Olga V., Doru-Abbasolu S., Uysal M., Koak-Toker N. The Effect of Resveratrol on Glycation and Oxidation Products in Plasma and Liver of Chronic Methylglyoxal-treated Rats. Yu H., Pardoll D., Jove R. STATs in Cancer Inflammation and Immunity: A Leading Role for STAT3. The aim of the present study was to investigate the effect of a micronized formulation of trans-resveratrol in humans with non-alcoholic fatty liver disease (NAFLD). Evans H.M., Howe P.R., Wong R.H. Resveratrol and liver: A systematic review - PMC - National Center for The high production of alcohol-derived acetate triggers mechanisms that promote inflammation [124,125,126,127]. HHS Vulnerability Disclosure, Help In another clinical study, 17 volunteers with T2D (type 2 diabetes) were treated with 150 mg/day of RV for 30 days, showing a decreased intrahepatic lipid content and systolic blood pressure. critical revision of the manuscript. Resveratrol Induces Extensive Apoptosis by Depolarizing Mitochondrial Membranes and Activating Caspase-9 in Acute Lymphoblastic Leukemia Cells. Licensee MDPI, Basel, Switzerland. Rivera et al. Furthermore, resveratrol has been shown to elicit a remarkable anti-angiogenic effect during the development of DENA-induced hepatocellular carcinogenesis, blocking VEGF (vascular endothelial growth factor) expression through HIF-1 (hypoxia-inducible factor-1) downregulation [89]. In these studies, dietary resveratrol prevented ethanol-induced lipid peroxidation in rats, resulting in a decrease in MDA (Malondialdehyde) content, an indicator of oxidative stress. The metabolic activities of cytochromes on alcohol metabolites cause the release of free radicals, which, in turn, stimulate inflammatory processes in the liver [128,129,130]. Wang L.F., Wang X.N., Huang C.C., Hu L., Xiao Y.F., Guan X.H., Qian Y.S., Deng K.Y., Xin H.B. Filardo S., Di Pietro M., Mastromarino P., Sessa R. Therapeutic Potential of Resveratrol Against Emerging Respiratory Viral Infections. It may also decrease pain and swelling, reduce levels of sugar in the blood, and . Are miRNA-103, miRNA-107 and miRNA-122 Involved in the Prevention of Liver Steatosis Induced by Resveratrol? Deschnes M., Belle S.H., Krom R.A., Zetterman R.K., Lake J.R. Approximately 25% of people carry at least one copy of the variant which increases risk of AD two-to-three-fold relative to those who carry the 3 variant. Espinoza J.L., Trung L.Q., Inaoka P.T., Yamada K., An D.T., Mizuno S., Nakao S., Takami A. Additionally, it is capable of altering the fatty acid composition of the liver cells. Category and Working Principle: Liv Pure is a dietary supplement that supports weight loss by improving liver function with the help of high-quality ingredients. Paracetamol Toxicity: Epidemiology, Prevention and Costs to the Health-care System. Timmers S., Konings E., Bilet L., Houtkooper R.H., van de Weijer T., Goossens G.H., Hoeks J., van der Krieken S., Ryu D., Kersten S., et al. To better understand paracetamol-induced liver injury, two mouse models have been used. The molecular mechanisms highlighted as underlying this process in cultured cells of hepatocytes included reduction in MDA (malondialdehyde) levels and increases in GPx and SOD levels, as well as an inhibition of mRNA expression of inflammatory mediators, including inducible NO, TNF- (tumour necrosis factor-), and IL-1 (interleukin-1) [53,54]. Synthesis Phase; PTEN/AKT: phosphatase and tensin homolog/protein kinase B; mTOR: target of rapamycin in mammals; ROS: reactive oxygen species; TNF: tumor necrosis factor; ALT: alanine aminotransferase; AKT-P: protein kinase B. An increase in mitochondrial capacity and stimulation of fat oxidation was observed, along with an improved oxidative capacity of skeletal muscles and preservation of fasting and postprandial fat oxidation. Received 2021 Feb 16; Accepted 2021 Mar 11. Baur J.A., Sinclair D.A. Apoptosis of Lymphocytes in Allograft in a Rat Liver Transplantation Model Induced by Resveratrol. Administration of 75 mg/day of RSV every 12 weeks to postmenopausal women with normal weight and glucose tolerance, highlighted no changes in inflammatory markers, body composition, resting metabolism, plasma lipids, in the liver, in the skeleton density muscles mass, and adipose tissue or insulin sensitivity [190]. Supplement Name: Liv Pure. Resveratrol Up-regulates Hepatic Uncoupling Protein 2 and Prevents Development of Nonalcoholic Fatty Liver Disease in Rats Fed a High-fat Diet. An official website of the United States government. Resveratrol: Protector of the Heart and Liver. Resveratrol might have many effects in the body, including expanding blood vessels and reducing blood clotting. 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. Attia S.M. Lee E.S., Shin M.O., Yoon S., Moon J.O. Its administration can significantly increase the survival rate after liver transplantation, reduce fat deposition and ischemia-induced necrosis and apoptosis in Wistar rats. Miura D., Miura Y., Yagasaki K. Restoration by Prostaglandins E(2) and F (2) (alpha) of Resveratrol-Induced Suppression of Hepatoma Cell Invasion in Culture. It would appear that a low dose of resveratrol (0.005%) is more effective than higher doses (0.02%) at reducing the development of hepatic steatosis, along with increases in body weight, plasma TAG levels, and total cholesterol levels [21]. randomized double-blind study, 38 overweight and obese subjects, Increase in mitochondrial capacity and stimulated fat oxidation, without leading to increased tissue-specific insulin sensitivity, Health condition associated with oxidative stress and inflammation, Plasma cytokine levels were measured over 48 h after oral administration in 10 healthy subjects, Repeated doses of resveratrol on circulating immune cells in healthy individuals, Increase in circulating T cells and regulatory T cells, 72 patients undergoing peritoneal dialysis randomly assigned to 12 week treatment of low-dose or high-dose trans-resveratrol or a placebo, Improvement in mean net UF volume and UF rate through a reduction in VEGF, Flk-1 (fetal liver kinase-1) and Ang-2 (angiopoietin) levels. Supplementation with High-dose Trans-resveratrol Improves Ultrafiltration in Peritoneal Dialysis Patients: A Prospective, Randomized, Double-blind Study. Apoptosis can be activated through two main pathways: the intrinsic pathway mediated by mitochondria-apoptosomes and the extrinsic pathway induced by death receptors [65,66]. Clment M.V., Hirpara J.L., Chawdhury S.H., Pervaiz S. Chemopreventive Agent Resveratrol, a Natural Product Derived from Grapes, Triggers CD95 Signaling-dependent Apoptosis in Human Tumor Cells. Resveratrol has been shown to elicit relevant antioxidant properties in a wide range of hepatic disorders [29,30,31,32,33]. Most of the clinical trials of resveratrol have focused on cancer, neurological disorders, cardiovascular diseases, diabetes, non-alcoholic fatty liver disease (NAFLD), and obesity. The Keap1-Nrf2-ARE Pathway as a Potential Preventive and Therapeutic Target: An Update. The aim of the present study was to investigate the effect of a micronized formulation of trans-resveratrol in humans with non-alcoholic fatty liver disease (NAFLD).
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