Grape seed extract supplementation in non-alcoholic fatty liver disease.

Background: Despite rising non-alcoholic fatty liver disease (NAFLD) prevalence and its impact on liver health, there's a lack of studies on grape seed extract's (GSE) effect on oxidative stress and quality of life (QoL) in NAFLD patients. This study aims to fill this gap by the potential benefits of GSE in reducing oxidative stress and improving QoL. Methods: In this randomized clinical trial study, fifty patients with NAFLD were randomly assigned to receive either 2 tablets of GSE containing 250 mg of proanthocyanidins or placebo (25 participants in each group) for two months. QoL was evaluated using the SF-36 questionnaire, and oxidative stress variables (TAC, MDA, SOD, GPx, CAT, and IL-6) were measured at the beginning and end of the study. Results: Compared with the control group, the group supplemented with GSE experienced greater reductions in IL-6 and MDA (3.14±1.43 pg/ml vs. 2.80±0.31 pg/ml; 4.16±2.09 µM vs. 4.59±1.19 µM, p for all <0.05), as well as greater increases in TAC, SOD, and GPx levels (0.18±0.08 mM vs. -0.03±0.09 mM; 10.5±6.69 U/ml vs. 8.93±1.63 U/ml; 14.7±13.4 U/ml vs. 8.24±3.03 U/ml, p for all <0.05). Furthermore, the QoL questionnaire showed that physical limitations, general health, and total physical health were significantly improved in the GSE group compared with the placebo (17.0±42.0 vs. -12.0±37.5; 3.80±14.8 vs. -3.92±9.55; 5.08 5.26 vs. -7.01±13.7, p for all <0.05). Conclusions: GSE can be effective in improving oxidative stress and QoL in patients with NAFLD. More studies are needed to confirm the results of this study.

Grape seed polyphenol extract and cognitive function in healthy young adults: a randomised, placebo-controlled, parallel-groups acute-on-chronic trial.

Grapes are polyphenol-rich, and grape juice intake has shown cognitive benefits in middle-aged females and older adults with mild cognitive impairment. Extracts obtained from grape seeds have similarly been associated with cognitive benefits in older adults. The aim of this research was to investigate whether a highly purified grape seed-derived polyphenol extract was associated with cognitive benefits in healthy young adults following a single acute dose, and chronically following repeated daily dosage over 12 weeks. Following an acute-on-chronic, parallel groups, randomised, double-blind, placebo-controlled design, sixty adults aged 18-30 consumed either a 400 mg grape seed polyphenol extract (GSPE, n = 30) or a placebo (n = 30). Cognitive function was assessed acutely at baseline and 2, 4 and 6 h post consumption, and chronically at 6 and 12 twelve weeks with a computerised battery of multiple cognitive tests. Mood was assessed with the Positive and Negative Affect Schedule. Linear marginal model analysis with baseline included as a covariate did not reveal a consistent pattern of cognitive benefits following the GSPE relative to the placebo either acutely or chronically when considering all outcome measures. GSPE was associated with some improvements in reaction time (acutely) and psychomotor skill (chronically), however the placebo was also associated with some benefits to reaction time and memory. Therefore, a 400 mg GSPE did not consistently improve cognitive function in healthy young adults. These findings suggest that younger, healthy populations are perhaps less sensitive to polyphenol extract doses <400mg relative to older, or cognitively compromised populations.

Solid Lipid Nanoparticles Administering Antioxidant Grape Seed-Derived Polyphenol Compounds: A Potential Application in Aquaculture.

The supply of nutrients, such as antioxidant agents, to fish cells still represents a challenge in aquaculture. In this context, we investigated solid lipid nanoparticles (SLN) composed of a combination of Gelucire® 50/13 and Precirol® ATO5 to administer a grape seed extract (GSE) mixture containing several antioxidant compounds. The combination of the two lipids for the SLN formation resulted in colloids exhibiting mean particle sizes in the range 139-283 nm and zeta potential values in the range +25.6-43.4 mV. Raman spectra and X-ray diffraction evidenced structural differences between the free GSE and GSE-loaded SLN, leading to the conclusion that GSE alters the structure of the lipid nanocarriers. From a biological viewpoint, cell lines from gilthead seabream and European sea bass were exposed to different concentrations of GSE-SLN for 24 h. In general, at appropriate concentrations, GSE-SLN increased the viability of the fish cells. Furthermore, regarding the gene expression in those cells, the expression of antioxidant genes was upregulated, whereas the expression of hsp70 and other genes related to the cytoskeleton was downregulated. Hence, an SLN formulation containing Gelucire® 50/13/Precirol® ATO5 and GSE may represent a compelling platform for improving the viability and antioxidant properties of fish cells.

Nrf2 regulates downstream genes by targeting miR-29b in severe asthma and the role of grape seed proanthocyanidin extract in a murine model of steroid-insensitive asthma.

CONTEXT: Grape seed proanthocyanidin extract (GSPE) is effective in treating severe asthma (SA). OBJECTIVE: To examine the relationship between Nrf2-miR-29b axis and SA, and to detect whether preventive use of GSPE relieves SA via it. MATERIALS AND METHODS: We recruited 10 healthy controls, 10 patients with non-severe asthma (nSA), and 9 patients with SA from February 2017 to December 2017. Peripheral blood mononuclear cells from these volunteers were extracted. A murine model of steroid-insensitive asthma was established in six-week-old female BALB/c mice that were sensitised and challenged with OVA, Al(OH)3 and LPS for 31 days. Mice in the treated groups were injected with DXM (5 mg/kg/d), with or without GSPE (100 mg/kg/d). Control group received PBS. We performed quantitative real-time PCR, western blot and luciferase reporter assay in animal and cell models. RESULTS: SA group demonstrated significantly lower concentrations of Nrf2 protein, Nrf2 mRNA, and miR-29b than nSA group and control group. Conversely, higher levels of platelet derived growth factor C (PDGFC), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), and collagen type III alpha 1 (COL3A1) were measured in SA than in the other two groups. PDGFC, PIK3R1, and COL3A1 were the target genes of miR-29b. GSPE + DXM significantly elevated the expression of Nrf2 (+188%), Nrf2 mRNA (+506%), and miR-29b (+201%), and significantly reduced the expression of PDGFC (-72%), PIK3R1 (-40%), and COL3A1 (-65%) compared with OVA + LPS. CONCLUSIONS: Nrf2-miR-29b axis is involved in the pathogenesis of SA. GSPE, as an adjuvant drug, maybe a potential therapeutic agent for SA.

Emu oil and grape seed extract reduce tumour burden and disease parameters in murine colitis-associated colorectal cancer.

Ulcerative colitis is an incurable condition whereby patients are at an increased risk of developing colorectal cancer (CRC). We aimed to investigate the combination of Emu oil (EO) and grape seed extract (GSE) in an azoxymethane (AOM)/dextran sulphate sodium (DSS) model of colitis-associated CRC (CA-CRC). C57BL/6 mice (n = 10/group) were injected i.p. with saline or AOM (7.4 mg/kg) and underwent three DSS/water cycles. Mice were orally-gavaged thrice weekly with water (80 µl), EO (80 µl), GSE (80 µl; 400 mg/kg) or combined EO/GSE (160 µl). Mice were euthanized on day 63. AOM/DSS induced significant bodyweight loss (max -21%) and increased disease activity index (DAI) (max +83%) throughout the trial (P < 0.05). EO (max -53%), GSE (max -51%) and EO/GSE (max -71%) reduced DAI scores in AOM/DSS mice in all DSS cycles (P < 0.05). EO/GSE-treatment in AOM/DSS mice resulted in further DAI reduction compared with EO (max -62%) and GSE (max -71%) alone (P < 0.05). AOM/DSS mice presented with severe colonoscopically-assessed colitis at all time-points, which was reduced by EO, GSE and EO/GSE (P < 0.05). EO, GSE and EO/GSE reduced the number of colonic tumours compared with AOM/DSS controls (P < 0.05). Myeloperoxidase (acute inflammation) and fluorescein isothiocyanate-dextran levels (intestinal permeability) were increased in AOM/DSS controls (P < 0.05). EO (-58%) and EO/GSE (-77%) reduced fluorescein isothiocyanate-dextran compared with AOM/DSS controls (P < 0.05), with no effect on myeloperoxidase. Histologically-assessed severity scores were increased in the distal colon of AOM/DSS mice compared with saline (P < 0.05), with no effect observed following treatment. The combination of EO and GSE improved clinical indicators and reduced colonic tumours in AOM/DSS treated mice, suggesting potential in CA-CRC management.

Effects of dietary grapeseed extract on performance, energy and nitrogen balance as well as methane and nitrogen losses of lambs and goat kids.

The influence of phenol-rich dietary grapeseed extract on performance, energy and N balance and methane production was determined in sixteen lambs and thirteen goat kids (body weight 20·5 and 19·0 kg, 2 months of age, day 1 of study). Half of the animals received a concentrate containing grapeseed extract, and the others received concentrate without grapeseed extract (total extractable phenols analysed 27 v. 9 g/kg dietary DM; concentrate and hay 1:1). Diets were fed for 7 weeks with 1 week for determining intake, excretion and gaseous exchange in metabolism crates and respiration chambers. Overall, there was an adverse effect of the phenolic diet on apparent N digestibility and body N retention. Faecal N loss as proportion of N intake increased while urinary N loss declined. Relative to N intake, total N excretion was higher and body N retention lower in goat kids than lambs. Diets and animal species had no effect on methane emissions. The saliva of the goat kids had a higher binding capacity for condensed tannins (CT). Goat kids on the phenolic diet had higher CT concentrations in faeces and excreted more CT compared with the lambs (interaction species × diet P < 0·001). The lambs had overall higher (P < 0·001) urinary phenol concentrations than the goat kids (2·19 v. 1·48 g/l). The negative effect on body N retention and lack of effect on methane emissions make the use of the extract in the dosage applied not appealing. Species differences need to be considered in future studies.

Neuroprotective benefits of grape seed and skin extract in a mouse model of Parkinson's disease.

Parkinson's disease is a neurodegenerative disorder characterized by the progressive loss of midbrain dopaminergic (mDA) neurons in the substantia nigra pars compacta, and it involves oxidative stress. Our goal was to evaluate the neuroprotective effect of Vitis vinifera red grape seed and skin extract (GSSE) in a model of Parkinson's disease. GSSE is very rich in phenolic compounds, such as flavonoids, anthocyanins, catechins and stilbenes, which are present in the pulp, seeds, and leaves of the fruit. GSSE is known for its antioxidant properties and has shown beneficial effects against oxidative injury in different organs, such as the kidneys, liver, heart and brain. In this study, we revealed the neuroprotective effect of GSSE on midbrain dopaminergic neurons both in vitro and in vivo. We used the neurotoxin 6-hydroxydopamine (6-OHDA), which induces oxidative damage and mimics the degeneration of dopaminergic neurons observed in Parkinson's disease. We found that GSSE was effective in protecting dopamine neurons from 6-OHDA toxicity by reducing apoptosis, the level of reactive oxygen species (ROS) and inflammation. Furthermore, we found that GSSE treatment efficiently protected against neuronal loss and improved motor function in an in vivo 6-OHDA model of Parkinson's disease (PD). Altogether, our results show that GSSE acts at multiple levels to protect dopamine neurons from degeneration in a model of PD.

Effects of Fish Oil and Grape Seed Extract Combination on Hepatic Endogenous Antioxidants and Bioactive Lipids in Diet-Induced Early Stages of Insulin Resistance in Rats.

Diacylglycerols (DAG) and ceramides have been suggested as early predictors of insulin resistance. This study was aimed to examine the combined effects of fish oil (FO) and grape seed extract (GSE) on hepatic endogenous antioxidants, DAG and ceramides in diet-induced early stages of insulin resistance. Thirty-five rats were fed one of the following diets: (1) a standard diet (STD group), (2) a high-fat high-sucrose diet (HFHS group), (3) an HFHS diet enriched with FO (FO group), (4) an HFHS diet enriched with GSE (GSE group) or (5) an HFHS diet enriched with FO and GSE (FO + GSE group). In the liver, endogenous antioxidants were measured using spectrophotometric and fluorometric techniques, and non-targeted lipidomics was conducted for the assessment of DAG and ceramides. After 24 weeks, the FO + GSE group showed increased glutathione peroxidase activity, as well as monounsaturated fatty acid and polyunsaturated fatty acid-containing DAG, and long-chain fatty acid-containing ceramides abundances compared to the STD group. The FO and GSE combination induced similar activation of the antioxidant system and bioactive lipid accumulation in the liver than the HFHS diet without supplementation. In addition, the FO and GSE combination increased the abundances of polyunsaturated fatty acid-containing DAG in the liver.

Protective effects of polydatin and grape seed extract in rats exposed to cadmium.

The current study aimed to investigate the protective role of polydatin (PD) and grape seed extracts (GSEs) against the effects of cadmium chlorine (CD) application in the rats. Forty-nine adult Wistar albino male rats were used in the study. Rats were assigned into control (saline), CD (5 mg/kg CdCI2), PD (120 mg/kg PD), GSE (120 mg/kg GSE), CD + PD (5 mg/kg CdCI2 + 120 mg/kg PD), CD + GSE (5 mg/kg CdCI2 + 120 mg GSE), and CD + PD + GSE (5 mg/kg CdCI2+120 mg/kg PD +120 mg/kg GSE) treatments (n = 7 per group). The treatments were administered orally for four weeks. CD accumulation was observed in all tissues studied except for the brain tissue. PD and GSE inhibited CD accumulation in erythrocytes and tissues at varying levels. The liver, kidney, brain, and testes showed extensive degenerative histopathological changes in CD group. Liver total oxidant status (TOS) in the CD group increased significantly compared to the control. TOS of kidney, brain, and testis suggested that PD and GSE did not show a strong antioxidant effect in these tissues. Malondialdehyde (MDA) levels in blood and liver raised significantly in CD-treated rats compared to controls. PD, GSE, and their combinations increased antioxidant potential in all tissues and decreased MDA levels in blood plasma and liver. Overall, the protective effects of PD were more effective than GSE. Results suggested that although the initiation of histopathological changes was present in all tissues, the initiating factor was not the oxidative stress in the tissues studied except for the liver and blood.

Nanoparticle delivery of grape seed-derived proanthocyanidins to airway epithelial cells dampens oxidative stress and inflammation.

BACKGROUND: Chronic respiratory diseases, whose one of the hallmarks is oxidative stress, are still incurable and need novel therapeutic tools and pharmaceutical agents. The phenolic compounds contained in grape are endowed with well-recognized anti-oxidant, anti-inflammatory, anti-cancer, and anti-aging activities. Considering that natural anti-oxidants, such as proanthocyanidins, have poor water solubility and oral bioavailability, we have developed a drug delivery system based on solid lipid nanoparticles (SLN), apt to encapsulate grape seed extract (GSE), containing proanthocyanidins. METHODS: Plain, 6-coumarin (6-Coum), DiR- and GSE-loaded SLN were produced with the melt-emulsion method. Physicochemical characterization of all prepared SLN was determined by photon correlation spectroscopy and laser Doppler anemometry. MTT assay (spectrophotometry) and propidium iodide (PI) assay (cytofluorimetry) were used to assess cell viability. Flow cytometry coupled with cell imaging was performed for assessing apoptosis and necrosis by Annexin V/7-AAD staining (plain SLE), cell internalization (6-Coum-SLN) and reactive oxygen species (ROS) production (SLN-GSE). NF-κB nuclear translocation was studied by immunofluorescence. In vivo bio-imaging was used to assess lung deposition and persistence of aerosolized DiR-loaded SLN. RESULTS: Plain SLN were not cytotoxic when incubated with H441 airway epithelial cells, as judged by both PI and MTT assays as well as by apoptosis/necrosis evaluation. 6-Coum-loaded SLN were taken up by H441 cells in a dose-dependent fashion and persisted into cells at detectable levels up to 16 days. SLN were detected in mice lungs up to 6 days. SLN-GSE possessed 243 nm as mean diameter, were negatively charged, and stable in size at 37 °C in Simulated Lung Fluid up to 48 h and at 4 °C in double distilled water up to 2 months. The content of SLN in proanthocyanidins remained unvaried up to 2 months. GSE-loaded SLN determined a significant reduction in ROS production when added 24-72 h before the stimulation with hydrogen peroxide. Interestingly, while at 24 h free GSE determined a higher decrease of ROS production than SLN-GSE, the contrary was seen at 48 and 72 h. Similar results were observed for NF-κB nuclear translocation. CONCLUSIONS: SLN are a biocompatible drug delivery system for natural anti-oxidants obtained from grape seed in a model of oxidative stress in airway epithelial cells. They feature stability and long-term persistence inside cells where they release proanthocyanidins. These results could pave the way to novel anti-oxidant and anti-inflammatory therapies for chronic respiratory diseases.

Morphometric and histopathological evaluation of the effect of grape seed proanthocyanidin on alveolar bone loss in experimental diabetes and periodontitis.

OBJECTIVE: Grape seed proanthocyanidine extract (GSPE) is a strong antioxidant derived from the grape seeds (Vitis vinifera, Terral J.F.) and has a polyphenolic structure with a wide range of biological activity. The aim of the present study was to evaluate the effects of GSPE on alveolar bone loss and histopathological changes in rats with diabetes mellitus and ligature-induced periodontitis. MATERIAL AND METHODS: Forty rats were divided into 6 study groups. Control (C, 6 rats) group, periodontitis (P, 6 rats) group, diabetes (D, 6 rats) group, diabetes and periodontitis (D+P, 6 rats) group, diabetes, periodontitis and 100 mg/kg/day GSPE (GSPE-100, 8 rats), and diabetes, periodontitis and 200 mg/kg/day GSPE (GSPE-200, 8 rats) group. Diabetes mellitus was induced by intraperitoneal injection of a single dose of streptozotocin (60 mg/kg). Periodontitis was induced via ligation method. Silk ligatures were placed at the mandibular right first molars. GSPE was administered by oral gavage. After 30 days, all rats were killed. Alveolar bone loss was measured morphometrically via a stereomicroscope. For histopathological analyses, Alizarin red staining, and matrix metalloproteinase (MMP)-8, vascular endothelial growth factor and hypoxia inducible factor (HIF)-1α immunohistochemistry were performed. Tartrate-resistant acid phosphatase-positive osteoclast cells and relative total inflammatory cells were also determined. RESULTS: The highest alveolar bone loss was observed in the D+P group (P < .05). GSP-200 group decreased alveolar bone loss (P < .05). The D+P group had the highest osteoclast counts, but the difference was not significant compared to the P, GSPE-100 and GSPE-200 groups (P > .05). The inflammation in the D+P group was also higher than the other groups (P < .05). The osteoblast numbers increased in the GSPE-100 and GSPE-200 groups compared to the P and D+P groups (P < .05). MMP-8 and HIF-1α levels were highest in the D+P group and GSPE significantly decreased these levels (P < .05). CONCLUSION: Within the limits of this animal study, it can be suggested that GSPE administration may decrease periodontal inflammation and alveolar bone loss via decreasing MMP-8 and HIF-1α levels and increase osteoblastic activity in diabetic rats with experimental periodontitis.

A high-fat high-sucrose diet affects the long-term metabolic fate of grape proanthocyanidins in rats.

PURPOSE: Polyphenol metabolites are key mediators of the biological activities of polyphenols. This study aimed to evaluate the long-term effects of a high-fat high-sucrose (HFHS) diet on the metabolism of proanthocyanidins from grape seed extract (GSE). METHODS: Adult female Wistar-Kyoto rats were fed a standard (STD) or HFHS diet supplemented or not with GSE for 16 weeks. PA metabolites were determined by targeted HPLC-MS/MS analysis. RESULTS: A lower concentration of total microbial-derived PA metabolites was present in urine and the aqueous fraction of faeces in the HFHS + GSE group than in the STD + GSE group. In contrast, a tendency towards the formation of conjugated (epi)catechin metabolites in the HFHS + GSE group was observed. CONCLUSIONS: These results show that a HFHS diet significantly modifies PA metabolism, probably via: (1) a shift in microbial communities not counteracted by the polyphenols themselves; and (2) an up-regulation of hepatic enzymes.

Protective effect of grape seed and skin extract against high-fat diet-induced dyshomeostasis of energetic metabolism in rat lung.

BACKGROUND: Obesity is currently one of the major epidemics of this millennium and affects poeples throughout the world. It causes multiple systemic complications as it significantly interferes with respiratory function. OBJECTIVE: We aimed in the present work to study the effect of high fat diet (HFD) on lung oxidative stress and energy metabolism alterations, as well as the putative protection afforded by grape seed and skin extract (GSSE). METHODS: We started by characterizing the GSSE and its composition using gas chromatography coupled to mass spectrometry (GC-MS). We used a rat model of high-fat-diet and we evaluated the effect of GSSE on oxidative stress and energetic disturbances induced by HFD. We analyzed the effect of HFD on lung oxidative status by assessing lipid oxidation level, non-protein thiols (NPSH) and superoxide anion level… We also evaluated the effect of HFD on creatine kinase (CK), malate dehydrogenase (MDH) and mitochondrial complex IV. RESULTS: HFD induced body weight gain, increased lung weight and lipid content without affecting insulinemia and dropped adiponectemia. HFD also provoked on lung oxidative stress characterized by increased carbonylation (+ 95%; p = 0.0045), decreased of NPSH (- 32%; p = 0.0291) and inhibition of antioxidant enzyme activities such as glutathione peroxidase (- 25%; p = 0.0074). HFD also altered lung intracellular mediators as superoxide anion O2¯ (+ 59%; p = 0.0027) and increased lung xanthine oxidase activity (+ 27%; p = 0.0122). HFD induced copper depletion (- 24%; p = 0.0498) and lead (- 51%: p = 0.0490) from the lung. Correlatively HFD decreased the copper associated enzyme tyrosinase (- 29%; p = 0.0500) and decreased glutamine synthetase activity (- 31%; p = 0.0027). HFD altered also lung energy metabolism by increasing CK activity (+ 22%; p = 0.0108) and decreasing MDH and mitochondrial complex IV activities (- 28%; p = 0.0120, - 31%; p = 0.0086 respectively). Importantly all these alterations were efficiently corrected with GSSE treatment. CONCLUSION: In conclusion, GSSE has the potential to alleviate the deleterious lipotoxic effect of HFD on lung and it could find potential application in the protection against HFD-induced lung complications.

Brain proteomic modifications associated to protective effect of grape extract in a murine model of obesity.

In recent years, the obesity epidemic has developed into a major health crisis worldwide. With current treatments limited to expensive, high-risk surgery and minimally efficacious pharmacotherapy, new therapeutic options are urgently needed to fight against this alarming trend. Though brain dysfunction has been studied linked to high fat diet (HFD) and grape seed and skin extract (GSSE) correction, the proteomic modifications linking the two effects on brain lipotoxicity are not well understood. To this end rats were exposed for 8 weeks to HFD treatment, to GSSE (500mg/kg BW) and to binary mixture of HFD and GSSE to gain insight into the potential pathways altered with metabolic disease and the protection afforded by GSSE. Significant modifications of brain proteins were detected using mass spectrometry-based differential proteomics. These proteins were mainly related to oxidative stress, glycolysis and calcium signaling. Additionally, proteins involved in the cytoskeleton were also affected by HFD treatment. Interestingly, whether up- or down regulated protein abundances, GSSE corrected most of the disturbances of HFD treatment. These findings provide impetus for future therapeutic investigation on GSSE against other metabolic disorders.

Oral administration of grape seed polyphenol extract restores memory deficits in chronic cerebral hypoperfusion rats.

Chronic cerebral hypoperfusion (CCH) has been recognized as an important cause of both vascular dementia and Alzheimer's disease (AD), the two most prominent neurodegenerative diseases causing memory impairment in the elderly. However, an effective therapy for CCH-induced memory impairment has not yet been established. Grape seed polyphenol extract (GSPE) has powerful antioxidant properties and protects neurons and glia during ischemic injury, but its potential use in the prevention of CCH-induced memory impairment has not yet been investigated. Here, CCH-related memory impairment was modeled in rats using permanent bilateral occlusion of the common carotid artery. A Morris water maze task was used to evaluate memory, the levels of acetylcholinesterase, choline acetyltransferase, acetylcholine were used to evaluate cholinergic function, and oxidative stress was assessed by measuring the enzyme activity of superoxide dismutase, glutathione peroxidase, malonic dialdehyde, and catalase. We found that oral administration of GSPE for 1 month can rescue memory deficits. We also found that GSPE restores cholinergic neuronal function and represses oxidative damage in the hippocampus of CCH rats. We propose that GSPE protects memory in CCH rats by reducing ischemia-induced oxidative stress and cholinergic dysfunction. These findings provide a novel application of GSPE in CCH-related memory impairments.

Chronic administration of grape-seed polyphenols attenuates the development of hypertension and improves other cardiometabolic risk factors associated with the metabolic syndrome in cafeteria diet-fed rats.

The effects of grape-seed polyphenols against the development of hypertension and other cardiometabolic conditions associated with the metabolic syndrome (MetS) were studied in rats fed a high-fat, high-carbohydrate diet, known as the cafeteria (CAF) diet. Two groups of Wistar rats were fed standard (STD) or CAF diets for 12 weeks. The CAF diet-fed rats were administered different doses of a low-molecular-weight grape-seed polyphenol extract (LM-GSPE) (25, 100 and 200 mg/kg per d) or vehicle daily, and the STD diet-fed rats were administered LM-GSPE (100 mg/kg per d) or vehicle using ten animals per group. Body weight (BW), waist perimeter (WP) and systolic and diastolic blood pressures (BP) by the tail-cuff method were recorded weekly. The animals were housed in metabolic chambers every 2 weeks to estimate daily food and liquid intakes and to collect faeces and urine samples. The plasma lipid profile was analysed at time 0 and on the 4th, 7th, 10th and 12th weeks of the experiment. Moreover, plasma leptin was measured at the end of the experiment. Results demonstrated that LM-GSPE, when administered with the CAF diet, attenuated the increase in BP, BW, WP and improved lipid metabolism in these animals. However, although the 25- and 100-mg/kg per d doses were sufficient to produce beneficial effects on BP and lipid metabolism, a 200-mg/kg per d dose was necessary to have an effect on BW and WP. The present findings suggest that LM-GSPE is a good candidate for a BP-lowering agent that can also ameliorate other conditions associated with the MetS.

Effect of different concentrations and application times of proanthocyanidin gels on dentin erosion.

PURPOSE: To analyze the effect of different concentrations and application times of proanthocyanidin gels on dentin before an erosive challenge in order to evaluate if there is a dose-response or application time-response relationship in the use of these gels for erosion prevention. METHODS: 80 bovine root dentin blocks were randomly and equally divided into 10 groups and treated according to the two factors under study (purified grape seed proanthocyanidin gel concentration and time of application): 0.05P1: 0.05% proanthocyanidin gel during 1 minute; 0.05P5: 0.05% proanthocyanidin gel during 5 minutes; 1P1: 1% proanthocyanidin gel during 1 minute; 1P5: 1% proanthocyanidin gel during 5 minutes; 5P1: 5% proanthocyanidin gel during 1 minute; 5P5: 5% proantho-cyanidin gel during 5 minutes; 10P1: 10% proanthocyanidin gel during 1 minute; 10P5: 10% proanthocyanidin gel during 5 minutes; Control 1: placebo gel during 1 minute; and Control 5: placebo gel during 5 minutes. The gels were applied over dentin blocks once before the first erosive challenge. After that, the blocks were subjected to three erosive cycles per day, during 5 days. Profilometry was used to quantify the dentin loss (µm). Data were analyzed by two-way ANOVA and Fisher's test (P< 0.05). RESULTS: Statistical analysis showed that there was no significant difference between the application times. The different concentrations of proanthocianidin gels presented similar results (P> 0.05). All tested gels resulted in significantly less wear when compared to the placebo gel. CLINICAL SIGNIFICANCE: Grape seed proanthocyanidin gels could be considered as a promising therapy to diminish erosive dentin wear because it may interact with the exposed collagen, enhancing the demineralized organic matrix stabilization, which acts as a barrier against the diffusion of the acids from erosion.

Resveratrol and Grape Extract-loaded Solid Lipid Nanoparticles for the Treatment of Alzheimer's Disease.

The aggregation of amyloid-ß peptide (Aß) has been linked to the formation of neuritic plaques, which are pathological hallmarks of Alzheimer's disease (AD). Various natural compounds have been suggested as therapeutics for AD. Among these compounds, resveratrol has aroused great interest due to its neuroprotective characteristics. Here, we provide evidence that grape skin and grape seed extracts increase the inhibition effect on Aß aggregation. However, after intravenous injection, resveratrol is rapidly metabolized into both glucuronic acid and sulfate conjugations of the phenolic groups in the liver and intestinal epithelial cells (within less than 2 h), which are then eliminated. In the present study, we show that solid lipid nanoparticles (SLNs) functionalized with an antibody, the anti-transferrin receptor monoclonal antibody (OX26 mAb), can work as a possible carrier to transport the extract to target the brain. Experiments on human brain-like endothelial cells show that the cellular uptake of the OX26 SLNs is substantially more efficient than that of normal SLNs and SLNs functionalized with an unspecific antibody. As a consequence, the transcytosis ability of these different SLNs is higher when functionalized with OX-26.

Effects of grape seed extract beverage on blood pressure and metabolic indices in individuals with pre-hypertension: a randomised, double-blinded, two-arm, parallel, placebo-controlled trial.

The aim of the present study was to test grape seed extract (GSE) as a functional ingredient to lower blood pressure (BP) in individuals with pre-hypertension. A single-centre, randomised, two-arm, double-blinded, placebo-controlled, 12-week, parallel study was conducted in middle-aged adults with pre-hypertension. A total of thirty-six subjects were randomised (1:1) to Placebo (n 18) or GSE (n 18) groups; twenty-nine of them completed all the protocol-specified procedures (Placebo, n 17; GSE, n 12). Subjects consumed a juice (167 kJ (40 kcal)) containing 0 mg (Placebo) or 300 mg/d GSE (150 mg) twice daily for 6 weeks preceded by a 2-week Placebo run-in and followed by 4-week no-beverage follow-up. Compliance was monitored. BP was measured at screening, 0, 6 and 10 weeks of intervention and blood samples were collected at 0, 3, 6 and 10 weeks of intervention. GSE significantly reduced systolic BP (SBP) by 5·6 % (P=0·012) and diastolic BP (DBP) by 4·7 % (P=0·049) after 6 weeks of intervention period, which was significantly different (SBP; P=0·03) or tended to be different (DBP; P=0·08) from Placebo. BP returned to baseline after the 4-week discontinuation period of GSE beverage. Subjects with higher initial BP experienced greater BP reduction; nearly double the effect size. Fasting insulin and insulin sensitivity tended to improve after 6 weeks of GSE beverage supplementation (P=0·09 and 0·07, respectively); no significant changes were observed with fasting plasma lipids, glucose, oxidised LDL, flow-mediated dilation or vascular adhesion molecules. Total plasma phenolic acid concentrations were 1·6 times higher after 6 weeks of GSE v. Placebo. GSE was found to be safe and to improve BP in people with pre-hypertension, supporting the use of GSE as a functional ingredient in a low-energy beverage for BP control.

The Protective Effect of Grape-Seed Proanthocyanidin Extract on Oxidative Damage Induced by Zearalenone in Kunming Mice Liver.

Although grape-seed proanthocyanidin extract (GSPE) demonstrates strong anti-oxidant activity, little research has been done to clearly reveal the protective effects on the hepatotoxicity caused by zearalenone (ZEN). This study is to explore the protective effect of GSPE on ZEN-induced oxidative damage of liver in Kunming mice and the possible protective molecular mechanism of GSPE. The results indicated that GSPE could greatly reduce the ZEN-induced increase of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities. GSPE also significantly decreased the content of MDA but enhanced the activities of antioxidant enzymes SOD and GSH-Px. The analysis indicated that ZEN decreased both mRNA expression levels and protein expression levels of nuclear erythroid2-related factor2 (Nrf2). Nrf2 is considered to be an essential antioxidative transcription factor, as downstream GSH-Px, γ-glutamyl cysteine synthetase (γ-GCS), hemeoxygenase-1 (HO-1), and quinone oxidoreductase 1 (NQO1) decreased simultaneously, whereas the pre-administration of GSPE groups was shown to elevate these expressions. The results indicated that GSPE exerted a protective effect on ZEN-induced hepatic injury and the mechanism might be related to the activation of the Nrf2/ARE signaling pathway.