Grape seed extract prevents chlorpyrifos-induced toxicity in rat liver through the modulation of phase I detoxification pathway.

Chlorpyrifos (CPF) poisoning is a public health problem for which there is not currently any effective prophylaxis. In this study, we investigated the protective effect of grape seed extract (GSE) against CPF-induced hepatotoxicity. Rats were daily treated either with CPF (2 mg/kg) or CPF and GSE (20 mg/kg) for 1 week, sacrificed, and their livers dissected for biochemical, molecular, and histopathological analyses. CPF generated liver dysfunction by altering carbohydrate, lipid, amino acid, ammonia and urea metabolism, and provoked mitochondrial impairment through disturbing tricarboxylic acid (TCA) cycle, oxidative phosphorylation (OXPHOS), and mitochondrial viability. CPF also induced cholinergic excitotoxicity along with oxidative stress and histopathological alterations. Interestingly, treatment with GSE prevented all the detrimental effects of CPF through the regulation of cytochrome P450 (CYP450) gene expression. Molecular docking analysis indicated that GSE-containing polyphenols acted as epigenetic modulators through inhibiting DNA (cytosine-5)-methyltransferase 1 (DNMT1), thus favoring the CYP2C6 detoxification pathway. Thereby, GSE might be a promising strategy in the protection of the liver against CPF toxicity.

Supplementation with grape seed extract, onion peel extract, or rosemary extract in the diet alleviates growth inhibition, liver damage, and oxidative stress induced by diquat in Lohmann chicks.

The present study aimed to assess the impact of grape seed extract (GSE), onion peel extract (OPE), and rosemary extract (ROE) on Diquat-induced growth restriction and oxidative stress in Lohmann chicks. A total of 200 chicks were randomly assigned to 5 diets: the positive control (PC) group, the negative control (NC) group, GSE group, OPE group, and ROE group. During the first 7 d of trial, compared with NC and PC groups, the GSE group enhanced average daily feed intake (ADFI). From day 8-21, diquat injection resulted in reduced growth performance, increased platelet volume distribution width (PWD), malondialdehyde (MDA) concentration, and activities of alanine aminotransferase (ALT) in chick serum; it also decreased total protein (TP), albumin (ALB), globulin (GLB) concentration, activities of superoxide dismutase (SOD) and glutathione S-transferase (GST) in chick serum; furthermore, it increased MDA concentration while decreasing GST activities in liver. The NC group exhibited lower average daily gain (ADG) than other groups. Compared with NC group, GSE group reduced ALT activities, MDA levels, and red cell distribution width (RDW), and PDW concentration; it also increased SOD, GST activities. The ROE group lowered ALT activities and MDA concentration. The OPE group decreased ALT activities, and MDA levels, RDW, and PDW concentration, and increased SOD activities of chicks. These results suggest that supplementing antioxidants in diets alleviated oxidative stress in chicks challenged by improving antioxidant capacity and liver function.

Grape seed tannin extract and polyunsaturated fatty acids affect in vitro ruminal fermentation and methane production.

Condensed tannins (CT), one of the most ubiquitous compounds in the plant kingdom, can modulate ruminal nutrient metabolism. Objectives were to study potential interactions of CT and polyunsaturated fatty acids (PUFA) on ruminal fermentation, biohydrogenation (BH), and methane production. Ruminal fluid obtained from lactating Holstein Friesian cows was used. All experiments were carried out as a completely randomized design with the same mixed diet: control (60:40 forage:concentrate) without supplement (CON), 2.5% soybean oil (SBO), and SBO + grape seed tannin extract (GSTE) at 0.2%, 0.4%, 0.6%, or 0.8% dietary DM (ST0.2, ST0.4, ST0.6, and ST0.8, respectively). Compared with CON (84.7 mM), total VFA concentration was not affected by SBO, but decreased (P < 0.001) with ST0.8 vs. ST0.6 (75.3 vs. 78.3 mM). Relative to CON, methane production was depressed (P < 0.001) by 17.7% and 28.0% in ST0.4 and ST0.8. The highest (P < 0.001) mean concentrations of c9,t11 CLA and C18:1 t11 were observed with ST0.4 compared with CON, but there was no difference between SBO and CT-containing diets. Disappearance of C18:2 c9,c12 was 49.1% vs. 50.3% in CON vs. SBO, whereas it ranged from 39.9% to 46.3% in CT-containing diets after 2 h incubation (P < 0.001). Concentrations of c9,t11 CLA with supplemental SBO and ST0.8 nearly peaked (P < 0.001) at 2 h incubation, but this fatty acid peaked (P > 0.05) at 6 h incubation and remained higher (P < 0.001; 15.9-17.0 µg/mL) at 24 h incubation with ST0.2, ST0.4, and ST0.6 compared with other diets (13.5-14.5 µg/mL). Compared with CON (50.6 µg/mL), concentration of C18:1 t11 with SBO and CT-containing diets reached a peak (P < 0.001; 241-265 µg/mL) at 12 h incubation. Concentration of C18:0 was 171%-231% higher (P < 0.001) with SBO and CT relative to CON at 24 h incubation. Overall, these results demonstrated that PUFA in SBO are more effective in modulating ruminal BH and CH4 production when combined with CT. However, high doses of added CT can reduce ruminal VFA concentration. Thus, a level of 0.4% GSTE added to diets containing 2.5% PUFA from plant origin might be suitable for optimizing ruminal fermentation and BH of C18:2 c9,c12 to fatty acid intermediates that could have beneficial effects to human health.

Condensed tannins can modulate methane emissions and ruminal biohydrogenation, but effects depend on type and dose. We used an in vitro fermentation system to investigate the effect of increasing doses (0%, 0.2%, 0.4%, 0.6%, and 0.8% dry matter) of grape tannin seed extract (GSTE) in a diet supplemented at 2.5% dry matter with soybean oil on methane production and biohydrogenation. Feeding soybean oil and GSTE at 0.6% and 0.8% reduced content of ruminal volatile fatty acids. Methane production (mL/g dry matter) was lower in the diet containing GSTE at 0.4%. Inclusion of GSTE at 0.2% and 0.4% increased concentration of C18:2 c9,c112, C18:3n3, c9,t11 conjugated linoleic acid and total polyunsaturated fatty acids after 24 h of incubation. The present findings contribute to a better understanding of the effect of condensed tannins from grape seed extract on ruminal fermentation and biohydrogenation.

Effects of grapeseed extract on doxorubicin-induced cardiotoxicity in rats.

BACKGROUND: Doxorubicin (DX) is used for the treatment of many types of cancer; however, a side effect of this agent is cardiotoxicity, which may lead to cardiomyopathy or cardiac failure. Oxidative stress is thought to play a major role in the development of cardiotoxic effects. Proanthocyanidins found in grapeseed (GS) extract may inhibit chemically induced lipid peroxidation and apoptosis caused by oxidative stress. We aimed to investigate the cardioprotective effects of GS extract against DX-induced cardiotoxicity. METHODS: A total of 28 male Sprague Dawley rats were grouped to receive: (a) standard nutrition (n = 7); (b) standard nutrition with an additional dose of 10 mg/kg DX (n = 7); (c) standard nutrition plus 100 mg/kg/day of GS (n = 7); (d) standard nutrition with 100 mg/kg/day of GS plus a single dose of 10 mg/kg DX. After 35 days the rats were decapitated and blood samples were taken for biochemical testing. Cardiac tissue samples were prepared for microscopy and histopathological evaluation. RESULTS: Rats in the DX group exhibited significant elevations in biomarkers such as troponin and NT-proBNP as well as in oxidative stress markers compared with all other groups. Histopathological examination corroborated these findings by demonstrating significant and severe structural injury in the cardiac tissue of DX rates. Moreover, rats in the DX + GS group had significantly lower cardiac injury than rats in the DX group according to both biochemical (troponin and NT-proBNP) and histopathological analyses. Serum malondialdehyde levels (a marker of oxidative stress) in the DX + GS rats were significantly lower than in the DX rats. CONCLUSION: Our findings suggest that GS may reduce the severity of DX-induced cardiotoxicity and thus has the potential to prevent cardiac injury in this setting.

Utilization of plant-based protein-polyphenol complexes to form and stabilize emulsions: Pea proteins and grape seed proanthocyanidins.

Plant-based proteins and polyphenols are increasingly being explored as functional food ingredients. Colloidal complexes were prepared from pea protein (PP) and grape seed proanthocyanidin (GSP) and the ability of the PP/GSP complexes to form and stabilize oil-in-water emulsions were investigated. The main interactions between PP and GSP were hydrogen bonding. The stability of PP-GSP complexes to environmental changes were studied: pH (2-9); ion strength (0-0.3 M); and temperature (30-90 °C). Emulsions produced using PP-GSP complexes as emulsifiers had small mean droplet diameters (~200 nm) and strongly negative surface potentials (~-60 mV). Compared to PP alone, PP-GSP complexes slightly decreased the isoelectric point, thermostability, and salt stability of the emulsions, but increased their storage stability. The presence of GSP gave the emulsions a strong salmon (red-yellow) color, which may be beneficial for some specific applications. These results may assist in the creation of more efficacious food-based strategies for delivering proanthocyanidins.

Grape seed proanthocyanidins improves mitochondrial function and reduces oxidative stress through an increase in sirtuin 3 expression in EA.hy926 cells in high glucose condition.

Proanthocyanidins are phenolic compounds abundant in the diet, commonly found in grapes and derivatives, foods known for their health-promoting benefits. There is previous evidence showing the antidiabetic activity of proanthocyanidins, however, their mechanisms of action have not been fully elucidated. This study evaluated the capacity of grape seed proanthocyanidins extract (GSPE) to modulate oxidative stress, nitric oxide levels, mitochondrial dysfunction, apoptosis, and sirtuin expression in endothelial cells EA.hy926 under high glucose condition. In addition, the possible toxic effects of GSPE was evaluated in a zebrafish embryos model. The results showed that GSPE was able to enhance cell viability and avoid the disturbance in redox metabolism induced by high glucose. Moreover, GSPE was able to avoid mitochondria dysfunction and the increased in p53 and poly-(ADP-ribose) polymerase expression induced by high glucose exposition. These effects were attributed to the increase in expression of sirtuin 3, a protein able to regulate mitochondrial function. GSPE in an effective concentration did not show toxic effects in zebrafish embryos model. Taken together, these data elucidate the key molecular target of GSPE for future pharmacological interventions in diabetic patients.

Effects of grape seed extract on performance, immunity, antioxidant capacity, and meat quality in Pekin ducks.

This study was conducted to evaluate the effects of grape seed extract (GSE) on growth performance, immunity, antioxidant capacity, relative organ weight, jejunum morphology, ileal microflora, and meat quality in Pekin ducks. A total of 1,500 female 1-day-old Pekin ducklings (52.0 ± 0.2 g) were blocked based on body weight (BW) and randomly allocated into 3 treatments with 10 replicates of 50 birds each. The experiment lasted for 6 wk, and dietary treatments included corn-soybean meal-based diet supplemented with 0, 0.01, and 0.02% GSE. The supplementation of GSE increased (P < 0.05) body weight gain (BWG) and final BW linearly but decreased (P < 0.05) feed-to-gain ratio (F/G) linearly during day (D) 22 to 42 and the entire experiment. The inclusion of GSE increased (P < 0.05) serum superoxide dismutase, glutathione peroxidase, total antioxidative capacity, catalase, complement4, immunoglobin G, interleukin-2, and interferon-γ linearly but decreased (P < 0.05) serum malondialdehyde linearly. The relative weight of carcass, breast meat, and spleen in GSE treatments was increased (P < 0.05) linearly, whereas the relative weight of abdominal fat was decreased linearly (P < 0.05). Birds fed GSE1 and GSE2 diets had lower (P < 0.05) cook loss, 2-thiobarbituric acid reactive substances, and drip loss on day 3 and 5 linearly but higher (P < 0.05) pH24h and water-holding capacity. The addition of GSE decreased (P < 0.05) jejunum crypt depth and ileal Escherichia coli counts linearly but increased (P < 0.05) jejunum villus height: crypt depth ratio and ileal Lactobacilli linearly. Taken together, the inclusion of GSE increased final BW and BWG, decreased F/G during day 22 to 42 and day 1 to 42, partially improved antioxidant activities, immunity, meat quality, and gut health in Pekin ducks.

Molecular hybridization of grape seed extract: Synthesis, structural characterization and anti-proliferative activity in vitro.

The grape seed extract (GSE) hybridized with medium-chain saturated fatty acids (decanoic acid) exhibited higher lipophilicity, antioxidant activity, and anti-proliferative activity than its parents. The chemical structures of individual hybridized GSE derivatives were identified as 3'-O-decanoyl catechin, 3'-O-decanoyl epicatechin, 3', 5'-2-O-decanoyl epigallocatechin, and 3', 4', 3″, 5″-4-O-decanoyl epicatechin gallate by HPLC-MS2 and 1H and 13C NMR. For growth inhibitory effect on HepG2 cells, hybridized GSE derivatives (EC50 = 44.38 µg/mL) were significantly (p < 0.01) stronger than natural GSE (EC50 = 60.83 µg/mL) due to increased lipophilicity. The effects of GSE derivatives on apoptosis and cell cycle in HepG2 cells were further evaluated by flow cytometry. The results showed that the percentage of apoptotic cells increased markedly in the presence of hybridized GSE derivatives. Moreover, hybridized GSE derivatives were capable of inducing cell cycle arrest in G1 phase. This research suggests that hybridized GSE derivatives are effective lipophilic antioxidants and show the potential as adjuvant therapy for cancer.

Phenolic Metabolites in Plasma and Thigh Meat of Chickens Supplemented with Grape Byproducts.

Grape byproducts are rich sources of polyphenols with powerful antioxidant and health-promoting effects. The impact of supplementing chicken diets with grape byproducts on plasma and thigh meat concentrations of phenolic metabolites was evaluated by analyzing samples by high-performance liquid chromatography quadrupole time of flight mass spectrometry. Chickens were fed three experimental diets: Control diet, Control+8% grape pomace, and Control+0.1% grape seed extract. In plasma, 32 phenolic metabolites were identified, some of which were conjugated catechin/epicatechin metabolites exclusively identified in chickens fed diets enriched in grape byproducts. Also, these chickens showed significantly higher plasmatic concentrations of 21 phenolic metabolites. In thigh meat, 14 phenolic metabolites were identified, but no differences were found between diets. Higher plasmatic tocopherol was found when supplementing diets with grape byproducts, while no changes were observed in meat. Thus, supplementing chicken diets with grape byproducts leads to a significant increase in the circulation of phenolic metabolites and tocopherol.

Effect of grape seed extract on maternal toxicity and in utero development in mice treated with zearalenone.

The aims of this study were to determine the polyphone content of grape seed extract (GSE) and to assess their protective effects against zearalenone (ZEN)-induced maternal toxicity and in utero development defects in mice. Five groups of pregnant mice were treated orally during days 6-13 of gestation as follows: control group, corn oil as vehicle (0.1 ml/mice)-treated group, ZEN-treated group (25 mg/kg b.w), GSE-treated group (150 mg/kg b.w.), and ZEN plus GSE-treated group. All animals were sacrificed on the 19th day of gestation and samples of bone marrow were collected for the micronucleus assay. The maternal and developmental toxicity were carried out. The HPLC analyses revealed that GES is rich in gallic acid, syringic acid, vanillin, quercetin, and coumaric acid. ZEN administration resulted in severe maternal and developmental toxicity which included an increase of micronuclei formation in bone marrow, decreased maternal weight gain, and litter weight. It also induces fetal growth retardation, increased number of the aborted dams and resorbed fetuses, abnormality of fetal bone ossification, and number of fetuses with a hematoma. GSE showed positive effects on the pregnant mice and the developing fetuses. Moreover, it counteracted the detrimental effects of ZEN in dams and fetuses. It could be concluded that polyphenols in GSE are a promising candidate to protect against ZEN toxicity in highly endemic areas.

Novel Antihypertensive Prodrug from Grape Seed Proanthocyanidin Extract via Acid-Mediated Depolymerization in the Presence of Captopril: Synthesis, Process Optimization, and Metabolism in Rats.

Grape seed extract contains a high content of proanthocyanidins that can be depolymerized into C-4-substituted (epi)catechin derivatives in the presence of nucleophiles. However, the biological and medicinal values of depolymerization products have been rarely investigated. Recently, we developed a novel depolymerization product (-)-epicatechin-4ß- S-captopril methyl ester (ECC) derived from the reaction of grape seed proanthocyanidin extract with captopril in the presence of acidified methanol. A central composite design was employed to select the most appropriate depolymerization temperature and time to obtain the target product ECC with a high yield. A total of 16 metabolites of ECC in rat urine, feces, and plasma were identified using liquid chromatography quadrupole time-of-flight tandem mass spectrometry. The in vivo results suggested that ECC could release captopril methyl ester and epicatechin, followed by the generation of further metabolites captopril and epicatechin sulfate conjugates. Therefore, ECC may be used as a potential prodrug with synergistic or additive hypotensive effects.

Black rhinoceros (Diceros bicornis) and domestic horse (Equus caballus) hindgut microflora demonstrate similar fermentation responses to grape seed extract supplementation in vitro.

The domestic horse is used as a nutritional model for rhinoceros maintained under human care. The validity of this model for browsing rhinoceros has been questioned due to high prevalence of iron overload disorder (IOD) in captive black rhinoceros (Diceros bicornis), which is associated with high morbidity and mortality. Iron chelators, such as tannins, are under investigation as dietary supplements to ameliorate or prevent IOD in prone species. Polyphenolic compounds variably affect microbial fermentation, so the first objective of this experiment was to evaluate the effects of grape seed extract (GSE; a concentrated source of condensed tannins; CT) on black rhinoceros hindgut fermentation. Equine nutrition knowledge is used to assess supplements for rhinoceros; therefore, the second objective was to evaluate the domestic horse model for black rhinoceros fermentation and compare fermentation responses to GSE using a continuous single-flow in vitro culture system. Two replicated continuous culture experiments were conducted using horse and black rhinoceros faeces as inoculum sources comparing four diets with increasing GSE inclusion (0.0%, 1.3%, 2.7% and 4.0% of diet dry matter). Diet and GSE polyphenolic compositions were determined, and sodium sulphite effect on neutral detergent fibre extraction of CT-containing forages was tested. Increasing GSE inclusion stimulated microbial growth and fermentation, and proportionally increased diet CT concentration and iron-binding capacity. Horse and black rhinoceros hindgut microflora nutrient digestibility and fermentation responses to GSE did not differ, and results supported equine fermentation as an adequate model for microbial fermentation in the black rhinoceros. Interpretation of these results is limited to hindgut fermentation and further research is needed to compare foregut digestibility and nutrient absorption between these two species. Supplementation of GSE in black rhinoceros diets up to 4% is unlikely to adversely affect hindgut nutrient digestibility or microbial viability and fermentation.

Effect of dietary supplementation of grape seed extract on the growth performance, lipid profile, antioxidant status and immune response of broiler chickens.

Grape seed extracts (GSE) contain several beneficial bioactive constituents; therefore, can be utilized as a potential feed additive in broiler chickens. An experiment was conducted to investigate the effect of supplementation of broiler chicken diets with GSE as a natural antioxidant at levels of 125, 250, 500, 1000 and 2000 ppm on the growth performance, serum lipid profile, liver glutathione-reduced, thigh muscle malondialdehyde and humoral immune response against Newcastle disease virus vaccines. This experiment was performed during the life-span of chickens from 0 to 42 days of age. The results of broilers fed on diet supplemented by GSE were compared with those fed on the basal diet (control) or the basal diet supplemented by butylated hydroxytoluene as a synthetic antioxidant (BHT, 125 ppm). No significant differences were observed in the growth performance, percent livability, total lipid, high and very low-density lipoprotein cholesterols when the use of GSE or BHT were compared with the control. Total cholesterol and low-density lipoprotein cholesterol were significantly decreased after intake of GSE compared with BHT in the feed diet. The glutathione-reduced level in liver tissues was significantly increased by inclusion of GSE, but not by BHT. Inclusion of GSE or BHT decreased significantly the malondialdehyde level found in meat tissue. The antibody titer against Newcastle disease virus vaccines was significantly elevated in 28 and 35-day-old broiler chickens fed with a diet supplemented with GSE or BHT, the former providing a higher response. It can be concluded that GSE can be used as an effective natural antioxidant and immunostimulant agent in broiler chicken diets, and that 125 to 250 ppm can be considered as the optimum dosage.

Grape seed procyanidin extract attenuates hypoxic pulmonary hypertension by inhibiting oxidative stress and pulmonary arterial smooth muscle cells proliferation.

Hypoxia-induced oxidative stress and excessive proliferation of pulmonary artery smooth muscle cells (PASMCs) play important roles in the pathological process of hypoxic pulmonary hypertension (HPH). Grape seed procyanidin extract (GSPE) possesses antioxidant properties and has beneficial effects on the cardiovascular system. However, the effect of GSPE on HPH remains unclear. In this study, adult Sprague-Dawley rats were exposed to intermittent chronic hypoxia for 4 weeks to mimic a severe HPH condition. Hemodynamic and pulmonary pathomorphology data showed that chronic hypoxia significantly increased right ventricular systolic pressures (RVSP), weight of the right ventricle/left ventricle plus septum (RV/LV+S) ratio and median width of pulmonary arteries. GSPE attenuated the elevation of RVSP, RV/LV+S, and reduced the pulmonary vascular structure remodeling. GSPE also increased the levels of SOD and reduced the levels of MDA in hypoxia-induced HPH model. In addition, GSPE suppressed Nox4 mRNA levels, ROS production and PASMCs proliferation. Meanwhile, increased expression of phospho-STAT3, cyclin D1, cyclin D3 and Ki67 in PASMCs caused by hypoxia was down-regulated by GSPE. These results suggested that GSPE might potentially prevent HPH via antioxidant and antiproliferative mechanisms.

Antioxidative and prooxidative effects in food lipids and synergism with α-tocopherol of açaí seed extracts and grape rachis extracts.

Extracts of açaí seed and of grape rachis alone or in combination with α-tocopherol were evaluated as antioxidants in (i) bulk soybean oil, (ii) soybean oil liposomes and (iii) soybean-oil/water emulsions. The extracts made with 57% aqueous ethanol showed an antioxidant activity not dependent on concentration for grape rachis extracts and a concentration-dependent prooxidative activity for açaí seed extracts in bulk soybean oil. Both the extracts, however, protected liposome suspensions and oil/water emulsions against lipid oxidation. Synergism was demonstrated when extracts were combined with α-tocopherol, effects explained by the solubility of extract components in the water-phase and of α-tocopherol in the lipid-phase. Phenolic profiling of the extracts by U-HPLC-ESI-LTQ-MS was used to identify active antioxidants. Açaí seed and grape rachis extracts served as good sources of procyanidins and flavan-3-ols, imparted high antioxidant activity especially when combined with α-tocopherol and are suggested for protection of food oil/water emulsions.

MicroRNA-19a/b mediates grape seed procyanidin extract-induced anti-neoplastic effects against lung cancer.

Oncomirs are microRNAs (miRNA) associated with carcinogenesis and malignant transformation. They have emerged as potential molecular targets for anti-cancer therapy. We hypothesize that grape seed procyanidin extract (GSE) exerts antineoplastic effects through modulations of oncomirs and their downstream targets. We found that GSE significantly down-regulated oncomirs miR-19a and -19b in a variety of lung neoplastic cells. GSE also increased mRNA and protein levels of insulin-like growth factor II receptor (IGF-2R) and phosphatase and tensin homolog (PTEN), both predicted targets of miR-19a and -19b. Furthermore, GSE significantly increased PTEN activity and decreased AKT phosphorylation in A549 cells. Transfection of miR-19a and -19b mimics reversed the up-regulations of IGF2R and PTEN gene expression and abrogated the GSE induced anti-proliferative response. Additionally, oral administration of leucoselect phytosome, comprised of standardized grape seed oligomeric procyanidins complexed with soy phospholipids, to athymic nude mice via gavage, significantly down-regulated miR-19a, -19b and the miR-17-92 cluster host gene (MIR17HG) expressions, increased IGF-2R, PTEN, decreased phosphorylated-AKT in A549 xenograft tumors, and markedly inhibited tumor growth. To confirm the absorption of orally administered GSE, plasma procyanidin B1 levels, between 60 and 90 min after gavage of leucoselect phytosome (400 mg/kg), were measured by LC/MS at week 2 and 8 of treatment; the estimated concentration that was associated with 50% growth inhibition (IC50) (1.3 µg/mL) in vitro was much higher than the IC50 (0.032-0.13 µg/ml) observed in vivo. Our findings reveal novel antineoplastic mechanisms by GSE and support the clinical translation of leucoselect phytosome as an anti-neoplastic and chemopreventive agent for lung cancer.

Influence of solvents on the composition of condensed tannins in grape pomace seed extracts.

The extracting effectiveness of some solvents (water, ethanol, acetone, ethyl acetate), used as pure or in binary and ternary mixtures, was studied for the extraction of seeds from the fermented pomace of Nebbiolo cv. The aqueous mixtures of acetone provided the highest extraction yields in total polyphenols and total flavonoids. Polyphenolic extracts were also obtained with aqueous mixtures of ethanol or acetone at variable concentrations, and the condensed tannins were quantified with the phloroglucinolysis method. The aqueous mixtures of acetone were more effective than the corresponding aqueous mixtures of ethanol. The solvent influenced the extraction yield and the composition of the extracts: with the increase of the yield, the mean degree of polymerization (mDP) of the condensed tannins increased. A significant correlation was noticed between mDP and the molar percentages of (+)-catechin as terminal unit (negative correlation), and of (-)-epicatechin and (-)-epicatechin-3O-gallate as extension units (positive correlation).

Green electrospun grape seed extract-loaded silk fibroin nanofibrous mats with excellent cytocompatibility and antioxidant effect.

Silk fibroin (SF) from Bombyx mori has an excellent biocompatibility and thus be widely applied in the biomedical field. Recently, various SF-based composite nanofibers have been developed for more demanding applications. Additionally, grape seed extract (GSE) has been demonstrated to be powerful on antioxidation. In the present study, we dedicate to fabricate a GSE-loaded SF/polyethylene oxide (PEO) composite nanofiber by green electrospinning. Our results indicated the successful loading of GSE into the SF/PEO composite nanofibers. The introduction of GSE did not affect the morphology of the SF/PEO nanofibers and GSE can be released from the nanofibers with a sustained manner. Furthermore, comparing with the raw SF/PEO nanofibrous mats, the GSE-loaded SF/PEO nanofibrous mats significantly enhanced the proliferation of the skin fibroblasts and also protected them against the damage from tert-butyl hydroperoxide-induced oxidative stress. All these findings suggest a promising potential of this novel GSE-loaded SF/PEO composite nanofibrous mats applied in skin care, tissue regeneration and wound healing.

Lack of tissue accumulation of grape seed flavanols after daily long-term administration in healthy and cafeteria-diet obese rats.

After ingestion flavanols are metabolized by phase-II enzymes and the microbiota and are distributed throughout the body depending on several factors. Herein we aim to evaluate whether flavanols are tissue-accumulated after the long-term administration of a grape seed polyphenol extract (GSPE) in rats and to study if compounds present in tissues differ in a cafeteria-diet obesity state. For that, plasma, liver, mesenteric white adipose tissue (MWAT), brain, and aorta flavanol metabolites from standard chow-diet-fed (ST) and cafeteria-diet-fed (CAF) rats were analyzed by high-performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) 21 h after the last 12-week-daily GSPE (100 mg/kg) dosage. Results showed that long-term GSPE intake did not trigger a flavanol tissue accumulation, indicating a clearance of products at each daily dosage. Therefore, results suggest that polyphenol benefits in a disease state would be due to a daily pulsatile effect. Moreover, obesity induced by diet also influences the metabolism and bioavailability of flavanols in rats.

Novel application of brain-targeting polyphenol compounds in sleep deprivation-induced cognitive dysfunction.

Sleep deprivation produces deficits in hippocampal synaptic plasticity and hippocampal-dependent memory storage. Recent evidence suggests that sleep deprivation disrupts memory consolidation through multiple mechanisms, including the down-regulation of the cAMP-response element-binding protein (CREB) and of mammalian target of rapamycin (mTOR) signaling. In this study, we tested the effects of a Bioactive Dietary Polyphenol Preparation (BDPP), comprised of grape seed polyphenol extract, Concord grape juice, and resveratrol, on the attenuation of sleep deprivation-induced cognitive impairment. We found that BDPP significantly improves sleep deprivation-induced contextual memory deficits, possibly through the activation of CREB and mTOR signaling pathways. We also identified brain-available polyphenol metabolites from BDPP, among which quercetin-3-O-glucuronide activates CREB signaling and malvidin-3-O-glucoside activates mTOR signaling. In combination, quercetin and malvidin-glucoside significantly attenuated sleep deprivation-induced cognitive impairment in -a mouse model of acute sleep deprivation. Our data suggests the feasibility of using select brain-targeting polyphenol compounds derived from BDPP as potential therapeutic agents in promoting resilience against sleep deprivation-induced cognitive dysfunction.