Inhibitory activities of grape bioactive compounds against enzymes linked with human diseases.

A quest for identification of novel, safe and efficient natural compounds, as additives in the modern food and cosmetic industries, has been prompted by concerns about toxicity and side effects of synthetic products. Plant phenolic compounds are one of the most documented natural products due to their multifarious biological applications. Grape (Vitis vinifera) is an important source of phenolic compounds such as phenolic acids, tannins, quinones, coumarins and, most importantly, flavonoids/flavones. This review crisply encapsulates enzyme inhibitory activities of various grape polyphenols towards different key human-ailment-associated enzymes: xanthine oxidase (gout), tyrosinase (hyperpigmentation), α-amylase and α-glucosidase (diabetes mellitus), pancreatic lipase (obesity), cholinesterase (Alzheimer's disease), angiotensin i-converting enzymes (hypertension), α-synuclein (Parkinson's disease) and histone deacetylase (various diseases). The review also depicts the enzyme inhibitory mechanism of various grape polyphenols and briefly discusses their stature as potential therapeutic and drug development candidates. KEY POINTS: • Nineteen major bioactive polyphenols from the grape/grape products and their disease targets are presented • Sixty-two important polyphenols as enzyme inhibitors from grape/grape products are presented • A thorough description and graphical presentation of biological significance of polyphenols against various diseases.

Grape Polyphenols in the Treatment of Human Skeletal Muscle Damage Due to Inflammation and Oxidative Stress during Obesity and Aging: Early Outcomes and Promises.

Today, inactivity and high-calorie diets contribute to the development of obesity and premature aging. In addition, the population of elderly people is growing due to improvements in healthcare management. Obesity and aging are together key risk factors for non-communicable diseases associated with several co-morbidities and increased mortality, with a major impact on skeletal muscle defect and/or poor muscle mass quality. Skeletal muscles contribute to multiple body functions and play a vital role throughout the day, in all our activities. In our society, limiting skeletal muscle deterioration, frailty and dependence is not only a major public health challenge but also a major socio-economic issue. Specific diet supplementation with natural chemical compounds such as grape polyphenols had shown to play a relevant and direct role in regulating metabolic and molecular pathways involved in the prevention and treatment of obesity and aging and their related muscle comorbidities in cell culture and animal studies. However, clinical studies aiming to restore skeletal muscle mass and function with nutritional grape polyphenols supplementation are still very scarce. There is an urgent need for clinical studies to validate the very encouraging results observed in animal models.

A critical review on grape polyphenols for neuroprotection: Strategies to enhance bioefficacy.

The aging of populations worldwide is driving greater demands for dietary polyphenols which have been recognized as promising prophylactic and/or therapeutic agents in the context of neurodegeneration, and are ubiquitously present in plant-based diets. In particular, grape-derived products encompass a wide array of phenolic compounds purported with multiple health benefits including neuroprotective efficacy. Despite the increasing preclinical and clinical evidence demonstrating high potential of grape polyphenol (GPP)-rich botanicals in preventing and attenuating diverse neurodegenerative disorders, the limited bioavailability of GPPs, especially in the brain, generates questions as to their applications and effectiveness in neuroprotection. To address this issue, significant research efforts have been made to enhance oral bioavailability of GPPs via application of novel strategies. This review highlights some critical issues related to the bioavailability and neuroprotective efficacy of GPPs and GPP-rich botanicals. The representative bioavailability-enhancing strategies are critically reviewed to provide practical solutions for augmenting the bioefficacy of GPP-rich botanicals. Synergistic applications of encapsulation techniques (for physiochemical protection and bypassing xenobiotic metabolism) and dietary intervention strategies involving modulation of gut microbiota (for generating more bioavailable phenolic metabolites) appear promising, and may substantially enhance the bioefficacy, especially the neuroprotective efficacy, of orally consumed GPPs.

Modulation of the Liver Protein Carbonylome by the Combined Effect of Marine Omega-3 PUFAs and Grape Polyphenols Supplementation in Rats Fed an Obesogenic High Fat and High Sucrose Diet.

Diet-induced obesity has been linked to metabolic disorders such as cardiovascular diseases andtype 2 diabetes. A factor linking diet to metabolic disorders is oxidative stress, which can damagebiomolecules, especially proteins. The present study was designed to investigate the effect of marineomega-3 polyunsaturated fatty acids (PUFAs) (eicosapentaenoic acid (EPA) and docosahexaenoic acid(DHA)) and their combination with grape seed polyphenols (GSE) on carbonyl-modified proteins fromplasma and liver in Wistar Kyoto rats fed an obesogenic diet, namely high-fat and high-sucrose (HFHS)diet. A proteomics approach consisting of fluorescein 5-thiosemicarbazide (FTSC) labelling of proteincarbonyls, visualization of FTSC-labelled protein on 1-DE or 2-DE gels, and protein identification byMS/MS was used for the protein oxidation assessment. Results showed the efficiency of the combinationof both bioactive compounds in decreasing the total protein carbonylation induced by HFHS diet in bothplasma and liver. The analysis of carbonylated protein targets, also referred to as the 'carbonylome',revealed an individual response of liver proteins to supplements and a modulatory effect on specificmetabolic pathways and processes due to, at least in part, the control exerted by the supplements on theliver protein carbonylome. This investigation highlights the additive effect of dietary fish oils and grapeseed polyphenols in modulating in vivo oxidative damage of proteins induced by the consumption ofHFHS diets.

Grape Polyphenols' Effects in Human Cardiovascular Diseases and Diabetes.

The consumption of fruits and vegetables, as well as foods enriched in bioactive compounds and nutraceuticals, has increased due to consumers' interest in the relevance of food composition for human health. Considerable recent interest has focused on bioactive phenolic compounds in grape, as they possess many biological activities, such as antioxidant, cardioprotective, anticancer, anti-inflammation, anti-ageing and antimicrobial properties. Observational studies indicate that the intake of polyphenol-rich foods improves vascular health, thereby significantly reducing the risk of hypertension, and cardiovascular disease (CVD). Other researchers have described the benefits of a grape polyphenol-rich diet for other types of maladies such as diabetes mellitus. This is a comprehensive review on the consumption of polyphenolic grape compounds, concerning their potential benefits for human health in the treatment of cardiovascular diseases and diabetes.

Addition of grape pomace extract to probiotic fermented goat milk: the effect on phenolic content, probiotic viability and sensory acceptability.

BACKGROUND: Grape pomace is a source of phenolic compounds, which are associated with health benefits in humans. Additionally, fermented dairy foods with probiotics can be good vehicles to deliver these bioactive compounds. The effects of the addition of grape pomace extract (GPE) on the total phenolic (TP) content, physico-chemical characteristics and viability of Lactobacillus acidophilus LA-5 or Lactobacillus rhamnosus HN001 in fermented goat milks prepared with grape juice were investigated. RESULTS: The TP concentration increased significantly in fermented milks with the addition of GPE. A protective effect of GPE on the viability of L. acidophilus was observed. However, after 14 days of storage, the populations of L. acidophilus were significantly lower when compared with those of L. rhamnosus, and only the last probiotic maintained its viability above 7 log CFU mL-1 throughout the period investigated. The sensory scores of flavor, color and overall acceptability of the fermented milk containing L. rhamnosus HN001 were significantly increased when GPE was added. CONCLUSION: The use of GPE might increase the functionality of probiotic fermented goat milk processed with L. rhamnosus HN001 and grape juice because grape polyphenols are known for their antioxidant properties and positive effect on the modulation of gut microbiota. © 2016 Society of Chemical Industry.

Nutrient depletion modifies cell wall adsorption activity of wine yeast.

Yeast cell wall is a structure that helps yeasts to manage and respond to many environmental stresses. The mannosylphosphorylation is a modification in response to stress that provides the cell wall with negative charges able to bind compounds present in the environment. Phenotypes related to the cell wall modification such as the filamentous growth in Saccharomyces cerevisiae are affected by nutrient depletion. The present work aimed at describing the effect of carbon and/or nitrogen limitation on the aptitude of S. cerevisiae strains to bind coloured polyphenols. Carbon- and nitrogen-rich or deficient media supplemented with grape polyphenols were used to simulate different grape juice conditions-early, mid, 'adjusted' for nitrogen, and late fermentations. In early fermentation condition, the R+G+B values range from 106 (high adsorption, strain Sc1128) to 192 (low adsorption, strain Σ1278b), in mid-fermentation the values range from 111 (high adsorption, strain Sc1321) to 258 (low adsorption, strain Sc2306), in 'adjusted' for nitrogen conditions the values range from 105 (high adsorption, strain Sc1321) to 194 (low adsorption, strain Sc2306) while in late fermentation conditions the values range from 101 (high adsorption, strain Sc384) to 293 (low adsorption, strain Sc2306). The effect of nutrient availability is not univocal for all the strains and the different media tested modified the strains behaviour. In all the media the strains show significant differences. Results demonstrate that wine yeasts decrease/increase their parietal adsorption activity according to the nutrient availability. The wide range of strain variability observed could be useful in selecting wine starters.

Syrah Grape Polyphenol Extracts Protect Human Skeletal Muscle Cells from Oxidative and Metabolic Stress Induced by Excess of Palmitic Acid: Effect of Skin/Seed Ripening Stage.

Metabolic skeletal muscle (SM) dysfunction, triggered by increased oxidative stress and mitochondrial impairment, is a pivotal contributor to obesity-associated insulin resistance (IR). Addressing obesity and SM IR demands substantial lifestyle changes including regular exercise and dietary adjustments that are difficult to follow over time. This prompted exploration of alternative approaches. Grape polyphenols (GPPs) have demonstrated a positive impact on metabolism, although few studies have focused on SM. Since grape polyphenolic content and composition depend on tissue and ripening, we explored the antioxidant potential of GPPs from skin (Sk) and seeds (Sd) extracted before veraison (Bv) and at mature (M) stages, on palmitate-induced IR in primary human SM cells. Despite their important difference in polyphenol (PP) content: Sd-BvPP > Sd-MPP/Sk-BvPP > Sk-MPP, all extracts reduced lipid peroxidation by 44-60%, up-regulated the heme-oxygenase 1 protein level by 75-132% and mitochondrial activity by 47-68%. Contrary to the other extracts, which improved insulin response by 50%, Sd-BvPP did not. Our findings suggest that compounds other than stilbenoids or anthocyanin-type molecules, present only in grape Sk, could play an active role in regulating SM oxidative and metabolic stress and insulin sensitivity, paving the way for further exploration of novel bioactive compounds.

Integral Valorization of Grape Pomace for Antioxidant Pickering Emulsions.

Full harnessing of grape pomace (GP) agricultural waste for the preparation of antioxidant Pickering emulsions is presented herein. Bacterial cellulose (BC) and polyphenolic extract (GPPE) were both prepared from GP. Rod-like BC nanocrystals up to 1.5 µm in length and 5-30 nm in width were obtained through enzymatic hydrolysis (EH). The GPPE obtained through ultrasound-assisted hydroalcoholic solvent extraction presented excellent antioxidant properties assessed using DPPH, ABTS and TPC assays. The BCNC-GPPE complex formation improved the colloidal stability of BCNC aqueous dispersions by decreasing the Z potential value up to -35 mV and prolonged the antioxidant half-life of GPPE up to 2.5 times. The antioxidant activity of the complex was demonstrated by the decrease in conjugate diene (CD) formation in olive oil-in-water emulsions, whereas the measured emulsification ratio (ER) and droplet mean size of hexadecane-in-water emulsions confirmed the physical stability improvement in all cases. The synergistic effect between nanocellulose and GPPE resulted in promising novel emulsions with prolonged physical and oxidative stability.

Moderate Wine Consumption and Health: A Narrative Review.

Although it is clearly established that the abuse of alcohol is seriously harmful to health, much epidemiological and clinical evidence seem to underline the protective role of moderate quantities of alcohol and in particular of wine on health. This narrative review aims to re-evaluate the relationship between the type and dose of alcoholic drink and reduced or increased risk of various diseases, in the light of the most current scientific evidence. In particular, in vitro studies on the modulation of biochemical pathways and gene expression of wine bioactive components were evaluated. Twenty-four studies were selected after PubMed, Scopus and Google Scholar searches for the evaluation of moderate alcohol/wine consumption and health effects: eight studies concerned cardiovascular diseases, three concerned type 2 diabetes, four concerned neurodegenerative diseases, five concerned cancer and four were related to longevity. A brief discussion on viticultural and enological practices potentially affecting the content of bioactive components in wine is included. The analysis clearly indicates that wine differs from other alcoholic beverages and its moderate consumption not only does not increase the risk of chronic degenerative diseases but is also associated with health benefits particularly when included in a Mediterranean diet model. Obviously, every effort must be made to promote behavioral education to prevent abuse, especially among young people.

Grape polyphenols decrease circulating branched chain amino acids in overfed adults.

Introduction and aims: Dietary polyphenols have long been associated with health benefits, including the prevention of obesity and related chronic diseases. Overfeeding was shown to rapidly induce weight gain and fat mass, associated with mild insulin resistance in humans, and thus represents a suitable model of the metabolic complications resulting from obesity. We studied the effects of a polyphenol-rich grape extract supplementation on the plasma metabolome during an overfeeding intervention in adults, in two randomized parallel controlled clinical trials. Methods: Blood plasma samples from 40 normal weight to overweight male adults, submitted to a 31-day overfeeding (additional 50% of energy requirement by a high calorie-high fructose diet), given either 2 g/day grape polyphenol extract or a placebo at 0, 15, 21, and 31 days were analyzed (Lyon study). Samples from a similarly designed trial on females (20 subjects) were collected in parallel (Lausanne study). Nuclear magnetic resonance (NMR)-based metabolomics was conducted to characterize metabolome changes induced by overfeeding and associated effects from polyphenol supplementation. The clinical trials are registered under the numbers NCT02145780 and NCT02225457 at ClinicalTrials.gov. Results: Changes in plasma levels of many metabolic markers, including branched chain amino acids (BCAA), ketone bodies and glucose in both placebo as well as upon polyphenol intervention were identified in the Lyon study. Polyphenol supplementation counterbalanced levels of BCAA found to be induced by overfeeding. These results were further corroborated in the Lausanne female study. Conclusion: Administration of grape polyphenol-rich extract over 1 month period was associated with a protective metabolic effect against overfeeding in adults.

Productive Performance, Egg Quality and Yolk Lipid Oxidation in Laying Hens Fed Diets including Grape Pomace or Grape Extract.

An experiment was conducted to assess in laying hens the effect of including grape pomace (GP, at 30 or 60 g/kg) or grape extract (GE, at 0.5 or 1.0 g/kg) on egg production, feed conversion ratio, protein and polyphenol digestibility, egg weight, egg quality, yolk fatty acid profile and oxidative stability of yolk lipids. No differences were detected among diets for egg production (83.8%, on average) or egg mass (56.8 g/d, on average). However, the average egg weight was lower (p = 0.004) for dietary treatments GP 30, GP 60 and GE 0.5 (67.5 g, on average) than for control hens (68.5 g). Accordingly, in hens fed the GP diets the proportion of XL eggs was lower (p = 0.008) than in control hens, while the proportion of M eggs was higher (p < 0.001) in hens fed the diets GP 30, GP 60 and GE 0.5 than in the control group. The dietary inclusion of both GP and GE decreased daily feed intake (120.9 vs. 125.3 g/d, p < 0.001) and the feed conversion ratio (2.09 vs. 2.18, p = 0.01). Feeding GP at 60 g/kg or GE reduced excreta protein digestibility (54.7 vs. 62.8%, p < 0.001), whereas all GP and GE diets showed higher excreta polyphenol digestibility than the control treatment (57.2 vs. 41.0%, p < 0.001). While yolk colour score was increased with all grape diets (8.12 vs. 7.34, p < 0.001), the dietary inclusion of GP, either at 30 or 60 g/kg, and that of GE at 1.0 g/kg increased the Haugh units of the albumen (80.8 vs. 76.4 Haugh units, p = 0.001). Shell thickness remained unaffected by dietary treatments (365.2 µm, on average). When included in the diet at 60 g/kg, GP reduced the proportion of saturated fatty acids in the yolk (31.6 vs. 32.9%, p = 0.001) and that of monounsaturated fatty acids (39.5 vs. 41.4%, p < 0.001), while it increased the percentage of polyunsaturated fatty acids (28.9 vs. 25.7%, p < 0.001). In fresh eggs, no significant differences were found for the malondialdehyde (MDA) concentration (0.146 mg/kg, on average). In stored eggs, the MDA amount was lower in the eggs of the laying hens fed GP at 60 g/kg than in the eggs of the control hens (1.14 vs. 1.64 mg/kg, p = 0.025). In conclusion, the inclusion of grape pomace, either at 30 or 60 g/kg, and grape extract at 1.0 g/kg in the diet of laying hens improved some egg quality traits, but feeding grape pomace resulted in a lower average weight of eggs. Nevertheless, feeding laying hens with diets containing grape pomace resulted in a higher antioxidant potential in egg yolk than dietary inclusion of grape extract.

Polyphenol Supplementation Did Not Affect Insulin Sensitivity and Fat Deposition During One-Month Overfeeding in Randomized Placebo-Controlled Trials in Men and in Women.

Two randomized placebo-controlled double-blind paralleled trials (42 men in Lyon, 19 women in Lausanne) were designed to test 2 g/day of a grape polyphenol extract during 31 days of high calorie-high fructose overfeeding. Hyperinsulinemic-euglycemic clamps and test meals with [1,1,1-13C3]-triolein were performed before and at the end of the intervention. Changes in body composition were assessed by dual-energy X-ray absorptiometry (DEXA). Fat volumes of the abdominal region and liver fat content were determined in men only, using 3D-magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) at 3T. Adipocyte's size was measured in subcutaneous fat biopsies. Bodyweight and fat mass increased during overfeeding, in men and in women. While whole body insulin sensitivity did not change, homeostasis model assessment of insulin resistance (HOMA-IR) and the hepatic insulin resistance index (HIR) increased during overfeeding. Liver fat increased in men. However, grape polyphenol supplementation did not modify the metabolic and anthropometric parameters or counteract the changes during overfeeding, neither in men nor in women. Polyphenol intake was associated with a reduction in adipocyte size in women femoral fat. Grape polyphenol supplementation did not counteract the moderated metabolic alterations induced by one month of high calorie-high fructose overfeeding in men and women. The clinical trials are registered under the numbers NCT02145780 and NCT02225457 at ClinicalTrials.gov and available at https://clinicaltrials.gov/ct2/show/NCT02145780 and https://clinicaltrials.gov/ct2/show/NCT02225457.

Evaluation of a Dietary Grape Extract on Oxidative Status, Intestinal Morphology, Plasma Acute-Phase Proteins and Inflammation Parameters of Weaning Piglets at Various Points of Time.

Reports of the underlying mechanisms of dietary grape extract (GE) in overcoming weaning challenges in piglets have been partly inconsistent. Furthermore, evaluations of the effects of GE at weaning in comparison to those of widely used therapeutic antibiotics have been scarce. To explore the mode of action of GE in selected tissues and plasma, we evaluated gut morphology, antioxidant and inflammation indices. Accordingly, 180 weaning piglets were allocated to three treatment groups: negative control (NC), NC and antibiotic treatment for the first 5 days of the trial (positive control, PC), and NC and GE (entire trial). The villus surface was positively affected by GE and PC on day 27/28 of the trial in the jejunum and on day 55/56 of the trial in the ileum. In the colon, NC tended (p < 0.10) to increase crypt parameters compared to PC on day 55/56. The PC group tended (p < 0.10) to increase catalase activity in the ileum and decrease Cu/Zn-SOD activity in the jejunum, both compared to NC. There were no additional effects on antioxidant measurements of tissue and plasma, tissue gene expression, or plasma acute-phase proteins. In conclusion, GE supplementation beneficially affected the villus surface of the small intestine. However, these changes were not linked to the antioxidant and anti-inflammatory properties of GE.

Taurisolo®, a Grape Pomace Polyphenol Nutraceutical Reducing the Levels of Serum Biomarkers Associated With Atherosclerosis.

Trimethylamine-N-oxide (TMAO) is a gut microbiota-derived metabolite recognized as strongly related to cardiovascular diseases (CVD), mainly increasing the risk of atherosclerosis development. Currently, no pharmacological approaches have been licensed for reduction of TMAO serum levels and conventional anti-atherosclerosis treatments only target the traditional risk factors, and the cardiovascular risk (CVR) still persist. This underlines the need to find novel targeted strategies for management of atherosclerosis. In this study we tested the ability of a novel nutraceutical formulation based on grape pomace polyphenols (Taurisolo®) in reducing both the serum levels of TMAO and oxidative stress-related biomarkers in humans (n = 213). After chronic treatment with Taurisolo® we observed significantly reduced levels of TMAO (-49.78 and -75.80%, after 4-week and 8-week treatment, respectively), oxidized LDL (oxLDL; -43.12 and -65.05%, after 4-week and 8-week treatment, respectively), and reactive oxygen species (D-ROMs; -34.37 and -49.68%, after 4-week and 8-week treatment, respectively). On the other hand, no significant changes were observed in control group. Such promising, the results observed allow indicating Taurisolo® as an effective nutraceutical strategy for prevention of atherosclerosis. Clinical Trial Registration: This study is listed on the ISRCTN registry with ID ISRCTN10794277 (doi: 10.1186/ISRCTN10794277).

Combining Grape Byproducts to Maximise Biological Activity of Polyphenols in Chickens.

Grape seeds (GS) and grape skins (GK) are natural sources of polyphenols with antioxidant capacity. An experiment was conducted to investigate in chickens the effect of including GS and GK (40 g/kg), individually or combined in different proportions (20 g/kg GS-20 g/kg GK; 30 g/kg GS-10 g/kg GK; 10 g/kg GS-30 g/kg GK), in a corn-soybean diet on growth performance, ileal and excreta contents of total extractable polyphenols (TEP) and tannins, ileal digestibility of protein, plasma and meat α-tocopherol concentration and lipid oxidation (assessed by measuring the thiobarbituric acid reactive substances, TBARS) of stored thigh meat. Neither growth performance parameters nor ileal digestibility of protein were affected by dietary treatments. As compared with control birds, chickens fed the grape byproduct diets showed higher ileal (p < 0.001) and excreta (p < 0.001) TEP and tannins contents. Dietary inclusion of grape byproducts increased α-tocopherol concentration both in plasma (p < 0.001) and in thigh meat (p < 0.01 at 1 d; p < 0.001 at 7 d), as compared with the control group. The highest plasma α-tocopherol concentrations were reached with the 30 g/kg GS-10 g/kg GK and 20 g/kg GS-20 g/kg GK combinations. On day 1 of meat storage, no differences on meat α-tocopherol concentration were found among the grape byproducts treatments but on day 7 of storage, the 20 g/kg GS-20 g/kg GK and 10 g/kg GS-30 g/kg GK combinations led to the highest α-tocopherol concentrations in chicken thigh meat. After seven days of refrigerated storage of meat, the TBARS value was lower in chickens fed the grape byproducts diets than in control birds (1.27 vs. 2.49 mg MDA/kg, p < 0.001). Moreover, among the different grape byproduct treatments, the lowest MDA values were reached with the diets containing GK at rates from 20 to 40 g/kg. In conclusion, dietary incorporation of 40 g/kg of GS and GK added separately or combined increased the plasma and meat α-tocopherol content. Furthermore, the combinations of GS and GK with a proportion of GK of at least 50% optimised α-tocopherol concentration both in plasma and in thigh meat and mitigated lipid oxidation in 7-day stored meat.

Grape Polyphenols Attenuate Diet-Induced Obesity and Hepatic Steatosis in Mice in Association With Reduced Butyrate and Increased Markers of Intestinal Carbohydrate Oxidation.

A Western Diet (WD) low in fiber but high in fats and sugars contributes to obesity and non-alcoholic fatty liver disease (NAFLD). Supplementation with grape polyphenols (GPs) rich in B-type proanthocyanidins (PACs) can attenuate symptoms of cardiometabolic disease and alter the gut microbiota and its metabolites. We hypothesized that GP-mediated metabolic improvements would correlate with altered microbial metabolites such as short chain fatty acids (SCFAs). To more closely mimic a WD, C57BL/6J male mice were fed a low-fiber diet high in sucrose and butterfat along with 20% sucrose water to represent sugary beverages. This WD was supplemented with 1% GPs (WD-GP) to investigate the impact of GPs on energy balance, SCFA profile, and intestinal metabolism. Compared to WD-fed mice, the WD-GP group had higher lean mass along with lower fat mass, body weight, and hepatic steatosis despite consuming more calories from sucrose water. Indirect and direct calorimetry revealed that reduced adiposity in GP-supplemented mice was likely due to their greater energy expenditure, which resulted in lower energy efficiency compared to WD-fed mice. GP-supplemented mice had higher abundance of Akkermansia muciniphila, a gut microbe reported to increase energy expenditure. Short chain fatty acid measurements in colon content revealed that GP-supplemented mice had lower concentrations of butyrate, a major energy substrate of the distal intestine, and reduced valerate, a putrefactive SCFA. GP-supplementation also resulted in a lower acetate:propionate ratio suggesting reduced hepatic lipogenesis. Considering the higher sucrose consumption and reduced butyrate levels in GP-supplemented mice, we hypothesized that enterocytes would metabolize glucose and fructose as a replacement energy source. Ileal mRNA levels of glucose transporter-2 (GLUT2, SLC2A2) were increased indicating higher glucose and fructose uptake. Expression of ketohexokinase (KHK) was increased in ileum tissue suggesting increased fructolysis. A GP-induced increase in intestinal carbohydrate oxidation was supported by: (1) increased gene expression of duodenal pyruvate dehydrogenase (PDH), (2) a decreased ratio of lactate dehydrogenase a (LDHa): LDHb in jejunum and colon tissues, and (3) decreased duodenal and colonic lactate concentrations. These data indicate that GPs protect against WD-induced obesity and hepatic steatosis by diminishing portal delivery of lipogenic butyrate and sugars due to their increased intestinal utilization.

Vasorelaxant Effects Induced by Red Wine and Pomace Extracts of Magliocco Dolce cv.

Several epidemiological studies demonstrate that moderate (red) wine consumption may afford protection against cardiovascular diseases. Protection is ascribed to the biological activity of wine components, many of which, however, are discarded during winemaking. In vitro rat thoracic aorta rings contracted with phenylephrine or KCl were used to assess the vasorelaxant activity of extracts from wine pomaces (seeds and skins) of the Calabrian autochthonous grape variety Magliocco dolce (Arvino). NMR spectroscopy was used to ascertain their chemical composition. Data demonstrate that seed and skin, but not must, extracts are capable of relaxing vascular preparations in an endothelium-dependent manner, similarly to the red wine extract, due to the presence of comparable amounts of bioactive constituents. In rings pre-contracted with 20-30 mM KCl, only seed extracts showed a moderate relaxation. The most efficacious vasodilating extract (wine) showed a good antioxidant profile in both [(2,2-diphenyl-1-picrylhydrazyl)acid] radical (DPPH) and [2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid)] radical (ABTS) assays. In conclusion, winemaking from Magliocco dolce grape can provide potentially health-promoting by-products useful in cardiovascular disease management.

Biodiversity and dairy traits of indigenous milk lactic acid bacteria grown in presence of the main grape polyphenols.

The present work was developed to select lactic acid bacteria (LAB) to be used as starter cultures in functional cheese production. The indigenous milk LAB populations were isolated from fermented raw ewes' milks (four bulks) added with 0.5 mg/mL of nine polyphenols commonly found in winery by-products. After 48 h of fermentation, all milks were characterized by an increase of LAB levels of about 3-4 Log cycles. All different colonies were purified and characterized for the main physiological and biochemical traits and then differentiated genetically at strain level and identified. Ten species belonging to the LAB genera Lactobacillus, Streptococcus, Enterococcus, Leuconostoc and Lactococcus were identified. Only Lactococcus lactis and Leuconostoc mesenteroides strains were evaluated for the technological traits including acidification and autolytic kinetics, diacetyl formation, exopolysaccharide production and generation of antimicrobial compounds. A total of four strains (Mise36, Mise94 Mise169 and Mise190) belonging to Lc. lactis displayed potential for production of cheeses containing grape polyphenols.

Effect of grape polyphenols on selected inflammatory mediators: A systematic review and meta-analysis randomized clinical trials.

Grapes contain different polyphenols and might prevent inflammation by reducing Nitric Oxide (NO) inactivation through antioxidative enzymes. The aim of this article was to demonstrate the effects of grape polyphenols on the selected inflammatory mediators, such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-a), and high-sensitivity C-reactive protein (hs-CRP). To find papers assessing the effects of grape polyphenols on inflammatory mediators, electronic data bases, including ISI web of science, PubMed/Medline, SCOPUS, and Google scholar, were searched up to March 2019. Delphi checklist was used for evaluating the qualities of the included articles. The protocol was registered in PROSPERO (No. CRD42019116695). The mean changes in the intervention and control groups were calculated by subtracting the end values from the baselines. Then, the difference between the two changes was measured and utilized as the effect size in meta-analysis. 9 and 8 articles were included in the systematic review and meta-analysis, respectively. Our results indicated that grape polyphenols did not reduce hs-CRP levels, but omission of one article could lead to a significant reduction in hs-CRP (Weight Mean Difference (WMD): -0.54 mg/L, 95 % CI: -1.02, -0.06; P=0.026, I2=0.0 %). Regarding IL-6 and TNF-α, no significant changes were observed in the intervention compared to the control group (WMD: 0.04 pg/mL, 95 % CI: -0.02, 0.28; P=0.744, I2=0.0 %, WMD: -0.10 pg/mL, 95 % CI: -0.25, 0.05; P=0.183, I2=0.0 %, respectively). We found no beneficial effects of grape polyphenols on the selected inflammatory mediators. Still, more studies with higher doses of polyphenols, longer treatment durations, different sources of grape polyphenols, and larger numbers of participants are required.