Doses Of Resveratrol Research Articles

Effects of polyphenols on activity of glycosyl hydrolases in the cecum of rats fed obesity inducing diets

The results of experimental studies indicate that the preventive and therapeutic effects of polyphenols in obesity are accompanied by a significant decrease in the severity of dysbiosis caused by the predominance of fats and simple carbohydrates in the diet, especially fructose, and the restoration of the functional state of the microbiota. The aim of the work was to study the effect of quercetin and resveratrol - polyphenols, widely represented in the daily human diet, on the activity of bacterial glycosidases in rats receiving diets high in fructose or fat and fructose. Material and methods. Using spectrophotometric analysis, the activity of β-galactosidase (Gal), β-glucosidase (Glu) and β-glucuronidase (Gluс) was studied in the content of the cecum of Wistar rats receiving a semi-synthetic diet and a 20% solution of fructose instead of drinking water (hfr diet) or a semi-synthetic diet with a high (30%) fat content and a 20% solution of fructose instead of drinking water (hf/hfr diet). Results and discussion. Feeding rats with the hfr diet for 20 weeks led to the suppression of Gal activity by 35, Glu by 46 and Gluс by 31%. With the inclusion of quercetin in the hfr diet at a dose of 34 mg/kg b.w. enzyme activity was restored to the control values and exceeded the level of activity in rats fed hfr ration without quercetin by 60, 100 and 47%, respectively, for Gal, Glu, and Gluс. Feeding rats with the hf/hfr diet for 10 weeks did not have a significant impact on the activity of bacterial enzymes. The inclusion of resveratrol in the hf/hfr diet at a dose of 10 mg/kg b.w. resulted in a decrease in Glu activity by 58 and Gluс by 28%, and an increase in resveratrol dose to 100 mg/kg b.w. caused further suppression of Gal activity by 30, Glu by 76 and Gluc by 64% comparative to the activity in rats on the hf/hfr diet without resveratrol. Conclusion. The obtained data suggest that quercetin restores reduced by hfr diet activity of glycosyl hydrolases of the cecum microflora of rats, most likely due to an increase in the representation of the types of enzyme activity carriers. The suppressive effect of resveratrol on the activity of glycosyl hydrolases of the cecum microflora of rats fed a hf/hfr diet may be the result of its direct action on enzymes and is not associated with the effect on the composition of the intestinal microbiota.

Resveratrol-Coated Balloon Catheters in Porcine Coronary and Peripheral Arteries.

Angioplasty aiming at vascular dilatation causes endothelial denudation and induces complex inflammatory responses that affect vascular healing, including delayed reendothelialization and excessive neointima proliferation. Resveratrol is known for multiple beneficial effects on the vessel wall after systemic treatment or sustained release from a stent. It is also used as an additive on drug-coated balloon catheters (DCB). In this study, the effect of a single dose of resveratrol, three days to four weeks after administration as a balloon coating during angioplasty, was investigated. Sixteen pigs underwent angioplasty with resveratrol-coated or uncoated balloon catheters in coronary and peripheral arteries. Vessels were overstretched by approximately 20% to enhance vessel wall injury and to produce persistent vessel wall irritation. A significantly reduced number of micro vessels and macrophages in the adventitia, as well as an improved reendothelialization of the vessel lumen, were observed in resveratrol-treated peripheral arteries. The coronaries had a much higher injury score compared to peripheral vessels. Resveratrol-dependent reduction of macrophages, micro vessels or acceleration of reendothelialization was not evident in the coronary vessels. Additionally, no significant effect on neointima proliferation and inflammation score in either vessel territory was observed as a result of resveratrol treatment. In conclusion, the results suggest that resveratrol diminishes the inflammatory response and promotes vascular healing in peripheral arteries. These same effects are absent in more severely injured coronary arteries.

<p>Resveratrol reduces liver endoplasmic reticulum stress and improves insulin sensitivity in vivo and in vitro</p>

Purpose: The aim of the study was to examine the effects of resveratrol upon hepatic endoplasmic reticulum stress (ERS) and insulin sensitivity in vivo and in vitro.Material and methods: C57BL/6J mice were fed a high-fat diet (HFD) for 8 weeks, and insulin resistance was evaluated by the intraperitoneal glucose tolerance test (IPGTT). Mice were then treated with resveratrol for 12 weeks and blood and liver samples collected. Blood biochemical indicators were determined by kits, liver protein expression was determined by western blot, and morphological changes were observed by histological staining. Palmitic acid (PA)-induced insulin-resistant HepG2 cells were established. Cells were exposed to 100, 50 or 20 μM resveratrol for 24 hrs, and proliferation/cytotoxicity was determined. Cells were divided into five groups: control, PA, PA + Rev (100 μM), PA + Rev (50 μM) and PA + Rev (20 μM) groups. After 24 hrs of treatment, cellular proteins were analyzed the same way as animal tissues.Results: The IPGTT confirmed that the insulin resistance model was established successfully. After resveratrol treatment, fasting blood glucose and cholesterol levels declined and the quantitative insulin sensitivity check index increased. Western-blot results showed that resveratrol-treated HFD mice had reduced hepatic levels of p-PERK, ATF-4 and TRIB3, and increased the levels of ATF-6, p-AKT and p-GSK3β. In the cell model, resveratrol with 100 and 50 μM enhanced ERS and insulin resistance, whereas 20 μM had beneficial effects, similar to the animal model.Conclusion: Resveratrol reduced hepatic ERS, thereby improving insulin sensitivity and glucose levels. However, high doses of resveratrol had harmful effects on cells, elevating ERS and insulin resistance. The safe dose of resveratrol needs further investigation.

The antinociceptive effect of resveratrol in bone cancer pain is inhibited by the Silent Information Regulator 1 inhibitor selisistat

To study the antinociceptive effect of single and repeated doses of resveratrol in a bone cancer pain model, and whether this effect is prevented by the Silent Information Regulator 1 (SIRT1) inhibitor selisistat. The femoral intercondylar bone of BALB/c mice was injected with 1000000 BJ3Z cancer cells. Bone resorption and tumour mass growth (measured by invivo X-ray and fluorescence imaging), as well as mechanical nociceptive thresholds (von Frey device) and dynamic functionality (rotarod machine), were evaluated during the following 4weeks. Acute resveratrol (100mg/kg i.p.) and/or selisistat (10mg/kg s.c.) were administered on day 14. Chronic resveratrol (100mg/kg i.p., daily) and/or selisistat (0.5μg/h s.c., Alzet pump) were administered between days 14 and 20. Tumour growth gradually incremented until day 31, while mechanical hyperalgesia started on day 3 after cancer cell injection. Acute resveratrol increased the mechanical threshold of pain (peaking at 1.5h), while the dynamic functionality decreased. Chronic resveratrol produced a sustained antinociceptive effect on mechanical hyperalgesia and improved the loss of dynamic functionality induced by the bone cancer tumour. Selisistat prevented all the effects of resveratrol. Acute and chronic resveratrol induces antinociceptive effect in the model of metastatic osseous oncological pain, an effect that would be mediated by SIRT1 molecular signalling.

The antidepressant- and anxiolytic-like effects of resveratrol: Involvement of phosphodiesterase-4D inhibition

Resveratrol is a natural non-flavonoid polyphenol found in red wine, which has numerous pharmacological properties including anti-stress and antidepressant-like abilities. However, whether the antidepressant- and anxiolytic-like effects of resveratrol are related to the inhibition of phosphodiesterase 4 (PDE4) and its subtypes remains unknown. The same holds true for the subsequent cAMP-dependent pathway. The first set of studies investigated whether resveratrol exhibited neuroprotective effects against corticosterone-induced cell lesion as well as its underlying mechanism. We found that 100 μM corticosterone induced PDE2A, PDE3B, PDE4A, PDE4D, PDE10 and PDE11 expression in HT-22 cells, which results in significant cell lesion. However, treatment with resveratrol increased cell viability in a dose- and time-dependent manner. These effects seem related to the inhibition of PDE4D, as evidenced by resveratrol dose-dependently decreasing PDE4D expression. In addition, the PKA inhibitor H89 reversed resveratrol's effects on cell viability. Resveratrol prevented corticosterone-induced reduction in cAMP, pVASP(s157), pCREB, and BDNF levels, indicating that cAMP signaling is involved in resveratrol-induced neuroprotective effects. Not to mention, PDE4D knockdown by PDE4D siRNA potentiated the effect of low dose of resveratrol on cAMP, pVASP, pCREB, and BDNF expression, while PDE4D overexpression reversed the effect of high dose of resveratrol on the expression of the above proteins. Finally, the subsequent in vivo data supports the in vitro findings, suggesting that resveratrol-induced antidepressant- and anxiolytic-like effects are mediated by PDE4D. Overall, these findings support the hypothesis that PDE4D-mediated cAMP signaling plays an important role in resveratrol's protective effects on stress-induced depression- and anxiety-like behavior.

Activation of AMPK in Human Placental Explants Impairs Mitochondrial Function and Cellular Metabolism

Adenosine monophosphate-activated protein kinase (AMPK) is a cellular energy sensor whose phosphorylation increases energy production. We sought to evaluate the placenta-specific effect of AMPK activation on the handling of nutrients required for fetal development. Explants were isolated from term placenta of 29 women (pregravid body mass index: 29.1 ± 9.9 kg/m2) and incubated for 24 hours with 0 to 100 µmol/L resveratrol or 0 to 1 mmol/L of 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR). Following treatment, uptake and metabolism of radiolabeled fatty acids and glucose were measured. Phosphorylation of AMPK was measured by Western blotting. Adenosine diphosphate (ATP) production was assessed using the mitochondrial ToxGlo assay kit. P < .05 was considered statistically significant. Resveratrol and AICAR increased AMPK phosphorylation in human placental explants. Exposure to resveratrol decreased the uptake of polyunsaturated fatty acids, arachidonic acid, and docosahexaenoic acid at 100 µmol/L ( P < .0001). Fatty acid oxidation was decreased by 100 µmol/L ( P < .05) resveratrol, while esterification was unchanged. Resveratrol decreased glucose uptake at the 50 and 100 µmol/L doses ( P < .05). Glycolysis was not significantly affected. AICAR had similar effects, decreasing fatty acid uptake and glycolysis ( P < .05). Production of ATP declined at doses found to decrease nutrient metabolism ( P < .05). Activation of AMPK in the human placenta leads to global downregulation of metabolism, with mitotoxicity induced at the doses of resveratrol and AICAR used to activate AMPK. Although activation of this pathway has positive metabolic effects on other tissues, in the placenta there is potential for harm, as inadequate placental delivery of critical nutrients may compromise fetal development.

Regulatory Effect of Resveratrol and Prednisolone on MDR1 Protein Expression in Acute Lymphoblastic Leukemia Cell Line (CCRF-CEM)

Objective:Chemotherapy is the most widely recognized technique to regard leukemia and also different sorts of human tumors. In any case, tranquilize protection has stayed as the primary test against the adequacy of medications. Besides, having different unfriendly impacts, chemotherapy drugs are getting to be traded by characteristic modalities for growth treatment. In such manner, natural segments, for example, resveratrol and prednisolone have been recognized to sharpen the leukemic cells to modified cell demise through an arrangement of complex procedures. In this investigation, we have analyzed effect of 15, 50 and 100μM of resveratrol and 700μM of prednisolone on the human multidrug protection quality 1 (MDR1) as a notable marker for cell sedate protection. We assessed the impact of resveratrol and prednisolone on MDR1 protein expression in the CCRF-CEM cell line as an agent for intense lymphoblastic leukemia. The investigation was planned to clear up whether. Materials and methods:CCRF-CEM cells linage get under drug treatment with use of resveratrol and prednisolone. Western blot use at 24 and 48 hours with different doses of resveratrol and prednisolone to analysis of MDR1 expression changes. Results:Effect of 15, 50, and 100 micro molar of resveratrol and 700 micro molars of prednisolone on CCRF-CEM cells led to the MDR1 decrease. Western blot use for evaluation of MDR1 protein expression changes. Conclusion:In the present study, we observed that resveratrol and prednisolone, with a dose-dependent effect, can reduce the expression of the MDR1 protein. This reduction of expression demonstrates that resveratrol and prednisolone can overcome to drug resistance created by MDR1.

GADD45α-targeted suicide gene therapy driven by synthetic CArG promoter E9NS sensitizes NSCLC cells to cisplatin, resveratrol, and radiation regardless of p53 status.

Background: GADD45α is a tumor suppressor protein often upregulated by environmental stresses and DNA-damage agents to cause growth arrest, apoptosis, tumor growth inhibition, and anti-angiogenesis. A novel suicide gene therapy vector pE9NS.G45α was engineered by cloning GADD45α opening reading frame downstream to the synthetic CArG promoter E9NS, which contains nine repeats of CArG element with modified core A/T sequence and functions as a molecular switch to drive the expression of GADD45α. The current study aims to determine the efficacy of this suicide gene therapy vector in combination with cisplatin, resveratrol, and radiation in NSCLC cell lines with various p53 statuses.Methods: Three NSCLC cell lines, H1299 (deleted p53), A549 (wild-type p53), and H23 (mutated p53), were examined in the present investigation to represent NSCLC with different p53 functions. MTT assay was conducted to select suitable doses of cisplatin, resveratrol, and radiation for gene therapy, and dual luciferase assay was performed to validate the activation of promoter E9NS. The efficacy of gene therapy combinations was evaluated by the amount of GADD45α expression, cell survival, and apoptosis.Results: All the combinations successfully activated promoter E9NS to elevate intracellular GADD45α protein levels and subsequently enhanced cell viability reduction and apoptosis induction regardless of p53 status.Conclusion: Our study demonstrates that GADD45α-targeted suicide gene therapy controlled by synthetic promoter E9NS sensitizes NSCLC cells to cisplatin, resveratrol, and radiation and is effective against NSCLC at least in vitro.

The Effect of Resveratrol dose and Duration of Treatment on Blood Pressure in Patients with Cardiovascular Disorders: A Systematic Review.

Hypertension is an important risk factor that causes many deaths in the world every year. Researchers continue to undertake studies to find an effective drug for reducing blood pressure. One of the phytochemicals that recently attracted the attention of researchers is resveratrol-polyphenol, found in grapes. The purpose of this systematic review is to investigate the effect of resveratrol as a cardioprotective agent effective in reducing hypertension in patients with hypertension. Studies and clinical articles from databases Scopus, Pubmed, Ovid and Cochrane have been collected until September 2017; the keywords are Blood Pressure, Hypertension, Hypertensive, Cardiovascular, and Resveratrol. Data from five studies with a total of 229 hypertensive and pre-hypertensive patients (men and women) showed that resveratrol plays an important role in reducing blood pressure. Resveratrol appears to have anti-hypertensive effects, depending on the dose and duration of treatment. Researchers attribute one of the important blood pressure reducing mechanisms of resveratrol to increasing levels of NO. Based on the results of this systematic review, it is suggested that more clinical studies be conducted to find the appropriate dose and duration of treatment.

Effects of resveratrol on oxidative stress in high fat diet /streptozocin induced diabetic wistar albino rats

Background: Diabetes mellitus is a common chronic disease. One of the pathophysiology is found to be oxidative stress. This study aims to evaluate the effect of resveratrol on oxidative stress in high fat diet (HFD)/streptozotocin induced diabetic rats.Methods: Wistar albino rats, fed with HFD rendered diabetic with streptozotocin, were divided into 6 groups, namely the diabetic control treated with vehicle (DC), standard control which received metformin (SC), test groups treated with 5,10, and 20 mg/kg b.w. of resveratrol and combination of half dose of metformin and resveratrol (10 mg/kg)(TC). A group of six normal animals served as normal control (NC), another six as HFD control. Fasting blood glucose, lipid profile and serum MDA and SOD were measured one week after induction of diabetes. The animals were then treated orally for 2 weeks after which the same parameters were repeated. The in-vivo results were analysed by one way ANOVA followed by Tukey’s multiple comparison test.Results: The DC group demonstrated a increase in the fasting blood glucose compared to NC, HFD control while a significant decrease in the fasting blood glucose was observed with SC, Test groups (p&lt;0.05) as compared to the DC group. TC showed a significant improvement in dyslipidemia compared to their baseline values (p&lt;0.05). There was significant change in the serum MDA level and SOD activity.Conclusions: Resveratrol improves oxidative stress in diabetic rats.

Resveratrol Improves Brain-Gut Axis by Regulation of 5-HT-Dependent Signaling in the Rat Model of Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS) is at high risk of co-morbid depression and anxiety, which reduces patients’ quality of life and increases the burden of health care costs. However, the pathophysiological mechanisms responsible for IBS still remain unknown. This study investigated the effects of resveratrol on stress-related depression, anxiety, intestinal and visceral dysfunction in rat model of IBS. Rats received chronic acute combining stress (CACS) for 22 days exhibited depression/anxiety-like behavior, visceral hypersensitivity and altered intestinal motility, as measured by the forced swimming, marble bury, abdominal withdrawal reflex (AWR) and intestinal tract motility (ITM) tests. These abnormalities were accompanied by reduced 5-hydroxytryptamine (5-HT) level in the hippocampus and increased 5-HT expression in the gut (ileum and colon) after CACS. Chronic treatment of IBS rats with resveratrol dose-dependently normalized CACS-induced both central nervous and peripheral dysfunction, which were consistent with its differentially regulating 5-HT contents in the brain and intestine. Pretreatment with the 5-HT1A receptor antagonist NAN-190 hydrobromide (NAN-190) prevented such effects. While sub-threshold of 5-HT1A receptor agonist 8-OH-DPAT potentiated the effects of low dose of resveratrol (10 mg/kg) on CACS-related behavioral abnormalities. Furthermore, resveratrol markedly increased PKA, p-cAMP-response element binding protein (p-CREB) and brain derived neurotrophic factor (BDNF) expression in the hippocampus of IBS rats, while decreased PKA, pCREB and BDNF levels were found in the ileum and colon. These effects were prevented by NAN-190, which were consistent with the behavioral changes. The present results suggested that resveratrol improved anti-IBS-like effects on depression, anxiety, visceral hypersensitivity and intestinal motility abnormality through regulating 5-HT1A-dependent PKA-CREB-BDNF signaling in the brain-gut axis.

Neonatal Resveratrol and Nicotinamide Riboside Supplementations Sex-Dependently Affect Beige Transcriptional Programming of Preadipocytes in Mouse Adipose Tissue.

Nutritional programming of the thermogenic and fuel oxidation capacity of white adipose tissue (WAT) through dietary interventions in early life is a potential strategy to enhance future metabolic health. We previously showed that mild neonatal supplementations with the polyphenol resveratrol (RSV) and the vitamin B3 form nicotinamide riboside (NR) have sex-dependent, long-term effects on the thermogenic/oxidative phenotype of WAT of mice in adulthood, enhancing this phenotype selectively in male animals. Here, we tested the hypothesis that these dietary interventions may impact the commitment of progenitor cells resident in the developing WAT toward brown-like (beige) adipogenesis. NMRI mice received orally from postnatal day 2–20 (P2–20) a mild dose of RSV or NR, in independent experiments; control littermates received the vehicle. Sex-separated primary cultures were established at P35 from the stromovascular fraction of inguinal WAT (iWAT) and of brown adipose tissue (BAT). Expression of genes related to thermogenesis and oxidative metabolism was assessed in the differentiated cultures, and in vivo in the iWAT depot of young (P35) animals. Neonatal RSV and NR treatments had little impact on the animals’ growth during early postnatal life and the expression of thermogenesis- and oxidative metabolism-related genes in the iWAT depot of young mice. However, the expression of brown/beige adipocyte marker genes was upregulated in the iWAT primary cultures from RSV supplemented and NR supplemented male mice, and downregulated in those from supplemented female mice, as compared to cultures derived from sex-matched control littermates. RSV supplementation had similar sex-dependent effects on the expression of thermogenesis-related genes in the BAT primary cultures. A link between the sex-dependent short-term effects of neonatal RSV and NR supplementations on primary iWAT preadipocyte differentiation observed herein and their previously reported sex-dependent long-term effects on the thermogenic/oxidative capacity of adult iWAT is suggested. The results provide proof-of-concept that the fate of preadipocytes resident in WAT of young animals toward the beige adipogenesis transcriptional program can be modulated by specific food bioactives/micronutrients received in early postnatal life.

The attenuative effects of oral resveratrol on renal changes induced by vanadium injection in rats

Introduction: Resveratrol (trans-3,5,4’-trihydroxystilbene) as a polyphenol with potential antioxidant and anti-inflammatory properties is known as an effective herbal medicine in different disorders in rats. Objectives: The present study was carried out to investigate the protective effects of oral consumption of resveratrol on vanadium induced renal injury in male Wistar rats. Materials and Methods: Animals received either ammonium metavanadate (AMV, 5 mg/ kg/d, (intraperitoneally; 14 consecutive days) or resveratrol solution (10 mg/kg and 50 mg/kg, gastric gavage) along with AMV treatment. The last group received resveratrol alone (50 mg/ kg, gastric gavage) for 4 weeks. Results: AMV injection caused progressive tubular damages resembling acute tubular necrosis. Microscopic views revealed tubular attenuation and blebbing. In addition, progressive peritubular congestion of the capillaries observed while no evidence of renal fibrosis was present in trichrome staining. Further, levels of the renal transforming growth factor β1 (TGF-β1) as an index of fibrosis had no difference in treated animals as compared with the control (13.4±1.2 versus 11.24±0.93 pg/mg protein) at the P&lt;0.05. However, in AMVtreated animals receiving the higher dose of resveratrol (50 mg/kg), the renal superoxide dismutase (SOD) activity, showed no difference as compared with the saline-treated rats (42±1.3 versus 51±1.4). Conclusions It is evident that AMV injection had no ability to induce renal fibrosis in rats while it evokes renal destructive lesions based on pathological results and enzyme levels. Moreover, our preliminary results suggest that resveratrol in high dose (50 mg/kg) could confer a minor role against AMV induced renal tubular necrosis in rats due to pathological results.

Resveratrol ameliorates gouty inflammation via upregulation of sirtuin 1 to promote autophagy in gout patients.

Resveratrol exerts an anti-inflammatory effect on collagen-induced arthritis and osteoarthritis in rats via activation of sirtuin 1 (SIRT1). Autophagy can be induced by resveratrol and leads to amelioration of interleukin-1 beta (IL-1β) release in vitro. We aimed to determine the anti-inflammatory mechanisms of resveratrol in patients with gout. Blood samples were obtained from patients with acute gout, intercritical gout (IG) and healthy controls (HC). The mRNA and protein levels of SIRT1 and nuclear factor-kappa B (NF-kB) p65 were determined in peripheral blood mononuclear cells (PBMCs) lysate from these patients. In the in vitro experiment, SIRT1, autophagy-related genes (beclin-1 and microtubule-associated protein 1 light-chain 3) and key genes involved in the gouty inflammatory pathway, including NF-κB p65, NLR family pyrin domain containing 3 (NLRP3), caspase-1 and IL-1β, were determined in PBMCs lysate or plasma from IG patients exposed to monosodium urate (MSU) crystals with or without resveratrol. The mRNA and protein levels of SIRT1 were downregulated in PBMCs from gout patients in comparison with HC. In the in vitro experiment, the protein levels of SIRT1 were downregulated in PBMCs from IG patients exposed to MSU crystals and were restored by resveratrol in a dose-dependent manner. Furthermore, high doses of resveratrol ameliorated the release of the inflammatory cytokine IL-1β. In addition, the mRNA levels of NLRP3 and NF-κB p65 were regulated by resveratrol, but caspase-1 and IL-1β were not. Furthermore, resveratrol promoted MSU-induced autophagy in PBMCs from patients with gout. These findings suggest that resveratrol ameliorates gouty inflammation via upregulation of SIRT1 to promote autophagy in patients with gout.

Modulation of fat metabolism and gut microbiota by resveratrol on high-fat diet-induced obese mice.

PurposeThe antioxidant resveratrol (RSV) has low bioavailability and can reach the colon to access the gut microbial ecosystem. RSV administration together with high-fat diet prevented abnormal changes of intestinal microbiota. However, whether or not RSV can reshape the intestinal microbiota of obese mice and alleviate obesity-related diseases remains to be studied. This study aimed to explore the role of RSV in alleviating high-fat-induced obesity and its relationship with oxidative stress and gut microbiota.MethodsMale C57BL/6 mice were divided into five groups and administered for 16 weeks with: standard diet (CON), high-fat diet (60% energy for lard, HFD), and HFD with low, medium, and high dose of RSV, 50, 75, and 100 mg/kg body weight administered daily via drinking water, respectively.ResultsMedium and high RSV treatment significantly prevented body weight gain, decreased relative weight of liver and adipose tissue compared with HFD (P<0.05). All doses significantly prevented HFD-induced increase of serum triglyceride, low density lipoprotein cholesterol, glucose, and endotoxemia (P<0.05). Medium and high dose also prevented chronic inflammation by decreasing serum interleukin-1 and tumor necrosis factor-alpha (P<0.05), and oxidative stress in liver and brain indicated by increase in superoxide dismutase, catalase, glutathione peroxidase activity (P<0.05). Formation of malondialdehyde was prevented by all doses compared with HFD (P<0.05). Both medium and high doses of RES increased alpha diversity of gut microbiota according to the Chao1 and Shannon indices (P<0.05). Medium dose induced obvious shift in gut microbiota composition according to principal component analysis. High dose of RSV effectively prevented HFD-induced increase of Coriobacteriaceae and Desulfovi-brionaceae (P<0.05), which show a significant correlation with body weight (r>0.8 P<0.00).ConclusionRSV prevented HFD-induced endotoxemia, oxidative stress, and gut microbiota change.

Effect of resveratrol-loaded nanostructured lipid carriers supplementation in cryopreservation medium on post-thawed sperm quality and fertility of roosters

The objective of this study was to assess the effect of resveratrol and resveratrol-loaded nanostructured lipid carriers (NLC) supplementation of semen extender on values for fertility variables of cryopreserved rooster semen. Rooster semen was cryopreserved in modified Beltsville extender containing 0 (control group), resveratrol at 20, 40 and 60 μM and resveratrol-loaded NLC at 20, 40 and 60 μM. After thawing, motility properties, abnormal morphology, viability, membrane functionality, mitochondrial activity, apoptotic status, malondialdehyde (MDA) and antioxidant activities (glutathione peroxidase (GPx), superoxide dismutase (SOD), and total antioxidant capacity (TAC)) and fertility potential (fertility and hatchability rates) were assessed. Using 40 μM resveratrol and resveratrol-loaded NLC improved total motility. The results indicated that sperm fertility and hatching rate, viability and membrane functionality were greater in the 40 μM resveratrol and resveratrol-loaded NLC compared to control group. The percentage of apoptotic spermatozoa in 40 μM resveratrol and resveratrol-loaded NLC group was less compared with the 60 μM resveratrol, 60 resveratrol-loaded NLC and control groups. Mitochondria activity was greater in the 40 μM resveratrol and resveratrol-loaded NLC extender group compared to 20 and 60 μM resveratrol, 60 resveratrol-loaded, and control groups. Also, the 40 μM resveratrol and resveratrol-loaded NLC extender group had a greater TAC and reduced MDA. Morphology and SOD were not affected by dose of resveratrol. The results indicate supplementation of the modified Beltsville extender with 40 μM resveratrol and resveratrol-loaded NLC resulted in a greater quality of frozen-thawed rooster sperm.

Potential Involvement of Peripheral Leptin/STAT3 Signaling in the Effects of Resveratrol and Its Metabolites on Reducing Body Fat Accumulation.

Bioactive compounds such as polyphenols have increased in importance in recent years, and among them, resveratrol (3,5,4′-trihydroxy-trans-stilbene) has generated great interest as an anti-obesity agent. Recent investigations have highlighted the importance of leptin signaling in lipid metabolism in peripheral organs. The aims of this study were (1) to investigate whether resveratrol can reduce fat accumulation in peripheral tissues by increasing their leptin sensitivity and (2) to identify which resveratrol-derived circulating metabolites are potentially involved in these metabolic effects. Serum leptin levels and the leptin signaling pathway were assessed in diet-induced obese rats. Moreover, serum metabolites of resveratrol were studied by ultra-high performance liquid chromatography–mass spectrometry (UHPLC-MSn). The daily consumption of 200 mg/kg of resveratrol, but not doses of 50 and 100 mg/kg, reduced body weight and fat accumulation in obese rats and restored leptin sensitivity in the periphery. These effects were due to increases in sirtuin 1 activity in the liver, leptin receptors in muscle and protection against endoplasmic reticulum (ER)-stress in adipose tissue. In general, the resveratrol metabolites associated with these beneficial effects were derived from both phase II and microbiota metabolism, although only those derived from microbiota increased proportionally with the administered dose of resveratrol. In conclusion, resveratrol reversed leptin resistance caused by diet-induced obesity in peripheral organs using tissue-specific mechanisms.

Resveratrol suppresses hyperglycemia-induced activation of NF-κB and AP-1 via c-Jun and RelA gene regulation.

Background: Resveratrol (RSV) provides several important biological functions in wide variety of cells. In this study, we investigated the molecular mechanisms underlying anti-inflammatory effect of RSV on HepG2 cells by assessing the gene expression of RelA and c-Jun- subunits of NF-κB and AP-1 transcription factors. Methods: HepG2 cells were settled in a serum- free medium with high concentrations of glucose (30 mM) and insulin (1 µM) overnight and were then incubated with RSV (5, 10, and 20 µM) for 24 and 48 hours. Real time quantitative polymerase chain reaction (qRT-PCR) was used to determine RelA and c-Jun expression. Results: RSV diminished hyperglycemia/hyperinsulinemia stimulated expression of c-Jun dose- dependently after 24 and 48 hours (p<0.05). In addition, RelA gene expression was decreased dose-dependently in all RSV doses after 48-hour incubation (p<0.05). Our results indicated that RSV may reduce NF-κB and AP-1 activity via RelA and c-Jun gene regulation. Conclusion: The findings of the present study demonstrated that RSV may be considered as a preventative and therapeutic agent for antagonizing inflammation in Hepatocellular carcinoma (HCC).

Resveratrol improves cardiac function and exercise performance in MI-induced heart failure through the inhibition of cardiotoxic HETE metabolites

Numerous epidemiological studies have demonstrated that approximately 40% of myocardial infarctions (MI) are associated with heart failure (HF). Resveratrol, a naturally occurring polyphenol, has been shown to be beneficial in the treatment of MI-induced HF in rodent models. However, the mechanism responsible for the effects of resveratrol are poorly understood. Interestingly, resveratrol is known to inhibit cytochrome P450 1B1 (CYP1B1) which is involved in the formation of cardiotoxic hydroxyeicosatetraenoic acid (HETE) metabolites. Therefore, we investigated whether resveratrol could improve MI-induced cardiac remodeling and HF in rats through the inhibition of CYP1B1 and its metabolites. To do this, rats were subjected to either sham surgery or a surgery to ligate the left anterior descending artery to induce a MI and subsequent HF. Three weeks post-surgery, rats with established HF were treated with control diet or administered a diet containing low dose of resveratrol. Our results showed that low dose resveratrol treatment significantly improves % ejection fraction in MI rats and reduces MI-induced left ventricular and atrial remodeling. Furthermore, non-cardiac symptoms of HF such as reduced physical activity improved with low dose resveratrol treatment. Mechanistically, low dose resveratrol treatment of rats with established HF restored levels of fatty acid oxidation and significantly improved cardiac energy metabolism as well as significantly inhibited CYP1B1 and cardiotoxic HETE metabolites induced in MI rats. Overall, the present work provides evidence that low dose resveratrol reduces the severity of MI-induced HF, at least in part, through the inhibition of CYP1B1 and cardiotoxic HETE metabolites.

Antioxidative, anti-inflammatory and hepatoprotective effects of resveratrol on oxidative stress-induced liver damage in tilapia (Oreochromis niloticus)

Resveratrol, a dietary polyphenol, has been shown to exert antioxidation, hepatoprotection, anti-inflammation and immunostimulation. However, the effects and underlying mechanism of resveratrol on liver injury in fish are still unclear. In the present study, we investigated the potential protective effects and mechanism of resveratrol on oxidative stress-induced liver damage in tilapia. Fish were fed diet containing four doses of resveratrol (0, 0.1, 0.3, and 0.6 g/kg diet) for 60 days, and then given an intraperitoneal injection of H2O2 or saline. The results showed that administration of resveratrol significantly ameliorated H2O2-induced liver injury. In serum and liver, resveratrol treatment suppressed the oxidative stress, as evidenced by the decline of lipid peroxidation level and increase of antioxidant activity. Resveratrol also activated erythroid 2-related factor 2 (Nrf2) signaling pathway and enhanced the heme oxygenase 1 (HO-1), NAD(P) H:quinone oxidoreductase 1 (NQO-1), glutathione S-transferase (GST) mRNA levels. Meanwhile, resveratrol treatment repressed TLR2-Myd88-NF-κB signaling pathway to decrease the inflammatory response in H2O2-induced liver injury as evidenced by the lower interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and IL-8 mRNA levels and higher IL-10 mRNA level. Moreover, resveratrol treatment attenuated immunotoxicity in liver of H2O2-treated fish, accompanied by upregulation of hepcidin (HEP), complement 3 (C3) and lysozyme (LZM) mRNA levels. Overall results suggested that the protection of resveratrol on H2O2-induced liver injury, inflammation and immunotoxicity was due to its antioxidant property and its ability to modulate the Nrf2 and TLR2-Myd88-NF-κB signaling pathways.