Grape Seed Polyphenols Research Articles

Alginate-millet starch composite matrices as novel carriers for controlled delivery of grape seed polyphenols: Preparation, characterization, and in vitro release behaviour

Grape seed polyphenols (GSP) were encapsulated in alginate-modified millet starch composite matrix using internal gelation. Millet starch was modified using ultrasound (US) for 10, 20, 30, and 40 min. The application of US reduced the long-range order and increased the short-range order of starch, consequently increasing its solubility. FESEM analysis revealed that US-treatment induced fissures and grooves on the surface of starch granules and disintegrated the starch particles. Particle size distribution analysis confirmed a significant reduction in mean particle size. US-treatment facilitated enhanced alginate-starch interactions owing to an increased surface area and improved hydrogen bonding, as corroborated by FTIR, XRD, and DSC results. The composite microencapsulates prepared from 40 min US-treated starch demonstrated the highest encapsulation efficiency (89.20 ± 1.10 %), heat and UV-light stability, and delayed GSP release in simulated gastrointestinal fluids. The best fit for the release behaviour of GSP from the composite microencapsulates was observed with Peppas-Sahlin model.

Effects of ultrasonic-assisted natural deep eutectic solvent on the extraction rate, stability and antifungal ability of polyphenols from Cabernet Sauvignon seeds

Ultrasonic-assisted extraction using a natural deep eutectic solvent (UAE-NADES) is an efficient method for extracting grape seed polyphenols (GSPs). In this study, response surface methodology was used to optimize the extraction of GSPs with UAE-NADES, and the theoretical extraction rate of GSPs was 139.014 mg GAE/g, the actual extraction rate was 135.78 ± 1.3 mg GAE/g. A pseudo-second-order kinetic extraction fitting was established to simulate the extraction process and mechanism (R2 > 0.99). Analysis of antioxidant capacity, Fourier-infrared spectroscopy and scanning electron microscopy revealed that UAE-NADES works synergetically to maintain the stability of extracted GSPs. The results of high-performance liquid chromatography showed that catechin (41.14 mg/g) is the main component of GSPs in the extract. The UAE-NADES extraction of GSPs can inhibit the growth of Alternaria alternata at 0.25 mg GAE/g, while the GSPs extracted by other methods can effectively inhibit the growth of Alternaria alternata at 0.35 mg GAE/g. Thus, this study demonstrates that UAE-NADES is a high-efficiency means of extracting GSPs and, in a wider sense, is a promising extraction technology for the green utilization of waste resources.

Grape-seed polyphenols inhibit AAA in mice via regulation of macrophage polarization

Abdominal aortic aneurysm (AAA) is characterized by macrophage polarization, and at present, no drug therapy is available. Although grape-seed polyphenols (GSP) showed an anti-AAA effect, the role of GSP in the phenotype shift in macrophages remains unknown. The main phenolic compounds in GSP were determined by LC-MS. Male C57BL/6 mice were divided into four equal groups, namely sham group, CaPO4 group, CaPO4+GSP low-dose group, and CaPO4+GSP high-dose group. GSP was administered intragastrically after CaPO4 application. Molecular expressions were histologically evaluated and analyzed by various staining assays and FACS. GSP administration inhibited CaPO4-induced AAA formation, which correlated with a decrease in macrophage infiltration and retainment of vascular smooth muscle layer as compared to those in the CaPO4 group. FACS assay showed that the GSP administration dose-dependently decreased the CD54 expression (low-dose group: 11.4 ± 2.1 % and high-dose group: 4.8 ± 1.4 % vs 23.2 ± 3.6 %; p < 0.05 and p < 0.01, respectively) and increased the CD206 expression of F4/80-positive cells in GSP-administered groups as compared with that in CaPO4-injured aortas in the CaPO4 group (low-dose group: 22.4 ± 3.3 % and high-dose group: 26.7 ± 4.2 % vs 8.1 ± 1.3 %; p < 0.05 and p < 0.01, respectively). GSP could be a pharmacologically potent agent in the treatment of AAA (Tab. 1, Fig. 3,Ref. 20). Text in PDF www.elis.sk Keywords: grape-seed polyphenols, abdominal aortic aneurysm, macrophage, inflammatory, polarization.

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 and type 2 diabetes. A factor linking diet to metabolic disorders is oxidative stress, which can damage biomolecules, especially proteins. The present study was designed to investigate the effect of marine omega-3 polyunsaturated fatty acids (PUFAs) (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) and their combination with grape seed polyphenols (GSE) on carbonyl-modified proteins from plasma 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 protein carbonyls, visualization of FTSC-labelled protein on 1-DE or 2-DE gels, and protein identification by MS/MS was used for the protein oxidation assessment. Results showed the efficiency of the combination of both bioactive compounds in decreasing the total protein carbonylation induced by HFHS diet in both plasma 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 specific metabolic pathways and processes due to, at least in part, the control exerted by the supplements on the liver protein carbonylome. This investigation highlights the additive effect of dietary fish oils and grape seed polyphenols in modulating in vivo oxidative damage of proteins induced by the consumption of HFHS diets.

Grape Seed Polyphenols Ameliorated Dextran Sulfate Sodium-Induced Colitis via Suppression of Inflammation and Apoptosis

Background: Ulcerative colitis (UC) is an inflammatory bowel disease. Its onset is typically gradual, usually followed by periods of spontaneous remission and subsequent relapses. Grape seed polyphenols (GSP), a natural product extracted from grape seeds, have strong anti-inflammatory functions. Objectives: In this study, we investigated whether GSP has an inhibitory effect on UC and its related mechanism or not. Methods: We induced UC by 2.5% dextran sulfate sodium (DSS) and GSP at different doses (500 and 750 mg/kg body weight per day) was administrated to the mice by gavage. Body weight, diarrhea, and bloody stool were recorded every day to evaluate disease activity index. Hemotoxylin-eosin staining and immunohistochemical staining were used to identify the histological damages and inflammatory infiltration in colon tissues. Real-time polymerase chain reaction was used to evaluate mRNA expression of interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α and the expression of phosphorylated-signal transducer and activator of transcription 3 (STAT3) and STAT3 were assessed by western blot. The immunofluorescent assay was used to evaluate the apoptosis of intestinal epithelial cells (IECs). Results: GSP could alleviate the loss of body weight, diarrhea, bloody stool, the mucosal damage, and inflammatory infiltration. GSP could also downregulate the mRNA expression of inflammatory cytokines IL-6, IL-1β, and TNF-α as well as the phosphorylation of STAT3 and ameliorate the apoptosis of IECs. Conclusions: Our study suggests that GSP has protective effects against DSS-induced UC, which may through suppression of inflammation and apoptosis.

Effects of dietary grape seed polyphenols supplementation during late gestation and lactation on antioxidant status in serum and immunoglobulin content in colostrum of multiparous sows1.

The aim of this study was to determine the effects of dietary grape seed polyphenols (GSP) supplementation during the late gestation and lactation period on reproductive performance, antioxidative status in serum, nutrient composition, and Ig content in colostrum of multiparous sows. On day 80 of gestation, a total of 64 sows with similar body condition were allocated to a completely randomized block design with 4 dietary treatments (n = 16 sows per treatment): 1) basal diet (CON, control group); 2) basal diet supplemented with 200 IU/kg vitamin E (200VE, positive control group); 3) basal diet supplemented with 200 mg/kg GSP (200GSP); and 4) basal diet supplemented with 300 mg/kg GSP (300GSP). The trial lasted 56 d until the piglets were weaned on day 21 of lactation. Reproductive performance, parameters of antioxidative status, and levels of progesterone (P4) and estradiol (E2) in serum, nutrient composition, and Ig content in colostrum of sows were determined. The number of dead fetuses was reduced, and farrowing survival was significantly improved in the litters from 300GSP-fed (P < 0.05). Preweaning survivability significantly increased in the litters from sows fed 200GSP and 200VE (P < 0.05). The activity of superoxide dismutase and glutathione peroxidase (GSH-Px) in the serum was significantly increased in sows fed 200GSP and 300GSP (P < 0.05). The activity of GSH-Px in the serum also significantly increased in sows fed 200VE (P < 0.05). Sows fed 300GSP had the greatest levels of P4 and E2 in the serum, which was significantly greater than sows fed 200VE and CON (P < 0.05). No significant differences were found among treatments for the content of solids-not-fat, fat, protein, and lactose in colostrum (P > 0.05). However, sows fed GSP had greater IgM and IgG content in colostrum compared with sows fed 200VE and CON (P < 0.05). In conclusion, dietary GSP supplementation during late gestation and lactation improved the farrowing survival and preweaning survivability, enhanced the antioxidant status and hormone levels in serum, and increased the IgM and IgG content in colostrum of sows.

Grape-seed Polyphenols Play a Protective Role in Elastase-induced Abdominal Aortic Aneurysm in Mice

Abdominal aortic aneurysm (AAA) is a kind of disease characterized by aortic dilation, whose pathogenesis is linked to inflammation. This study aimed to determine whether grape-seed polyphenols (GSP) has anti-AAA effects and what mechanism is involved, thus to find a way to prevent occurrence and inhibit expansion of small AAA. In our study, AAA was induced by incubating the abdominal aorta of the mice with elastase, and GSP was administrated to the mice by gavage at different doses beginning on the day of the AAA inducement. In in vivo experiments, 800 mg/kg GSP could significantly reduce the incidence of AAA, the dilatation of aorta and elastin degradation in media, and dramatically decrease macrophage infiltration and activation and expression of matrix metalloproteinase (MMP) −2 and MMP-9 in the aorta, compared to the AAA model group. Meanwhile, 400 mg/kg GSP could also but not completely inhibit the occurrence and development of AAA. In in vitro experiments, GSP dose-dependently inhibited mRNA expression of interleukin (IL)-1β, IL-6 and monocyte chemoattractant protein-1 (MCP-1), and significantly inhibited expression and activity of MMP-2 and MMP-9, thus prevented elastin from degradation. In conclusion, GSP showed great anti-AAA effects and its mechanisms were related to inhibition of inflammation.

Study on hypolipidemic and anti-atherosclerosis effects of grapeseed polyphenols

Aim: To study hypolipidemic and anti-atherosclerosis effects and mechanisms of grapeseed polyphenols (GSP) in LDLR-/- mice.

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.

In vitro release of grape-seed polyphenols encapsulated from uncoated and chitosan-coated liposomes

Grape-seed extract (GSE), a rich source for polyphenols, was incorporated into liposomes (1.1% w/w soy lecithin) using high-pressure homogenization (22,500psi). A chitosan coating (1% w/w) was used to obtain more stable liposomes. Physiochemical properties (ζ-potential, mean particle size) of all liposomes were analyzed. In vitro release of GSE-polyphenols from various liposomes was investigated by measuring the total phenolic content of the dialysate (acetate buffer, pH3.8±0.1, 25mM) over time. Diverse kinetic models were used to describe the release of the polyphenols incorporated from liposomes. Z-average particle diameters increased with the incorporation of GSE and chitosan coating. Chitosan-coated liposomes containing GSE had larger particle sizes than coated liposomes without GSE. The ζ-potential changed from −38mV in uncoated liposomes to +65mV in coated liposomes. Entrapment efficiency for uncoated and coated liposomes was 88.2±4.7% and 99.5±2.3%, respectively. The release rate increased gradually by increasing time. In vitro release of GSE polyphenols from both uncoated and coated liposomes followed an exponential equation (first order Q(t)=a·(1−exp(−k·t))). The release from coated liposomes was much lower than uncoated liposomes. The release rate after 24h from uncoated liposomes was 0.55 and from coated liposomes was 0.24. This study indicates that the release of bioactive compounds from liposomes can be reduced by coating with chitosan, allowing an application of coated liposomes with a controlled release of GSE polyphenols in water-based foods.

Electrospun grape seed polyphenols/gelatin composite fibers contained silver nanoparticles as biomaterials

GSP/gelatin composite nanofiber membranes containing silver nanoparticles were successfully fabricated as a novel biomaterial by electrospinning. The silver nanoparticles (AgNPs) were synthesized with the grape seed polyphenols (GSP) as reducing agent in aqueous solution of gelatin, and then the GSP/gelatin/AgNPs mixed solution was electrospun into nanofibers at 55 °C. The scanning electron microscopy (SEM) confirmed that the composite fibers were uniform and the average fiber diameter ranged between 150 nm and 230 nm with an increase in applied potentials from 14 kV to 22 kV. And the transmission electron microscopy (TEM) showed that silver nanoparticles distributed individually in the fibers with the average particle size of about 11 nm. Furthermore, the ultraviolet visible spectrophotometer (UV-vis spectroscopy) test demonstrated that all of Ag+ converted to Ag0 when the concentration of gelatin was 24 wt% and the mass ratio of GSP to AgNO3 was about 5:2. The antibacterial activities of the fiber membranes against E.coli and S.aureus were measured via a shake flank test and demonstrated good performance after the importation of silver nanopaticles. Cytotoxicity testing also revealed that fiber membranes contained silver nanoparticles had no cyto-toxic. All the results indicated that the GSP was effective for the formation and stabilization of silver nanoparticles in composite nanofibers mats which had the potential for applications in antimicrobial tissue engineering and wound dressing.

Effects of vitamin E, vitamin C and polyphenols on the rate of blood pressure variation: results of two randomised controlled trials.

High blood pressure (BP) variability, which may be an important determinant of hypertensive end-organ damage, is emerging as an important predictor of cardiovascular health. Dietary antioxidants can influence BP, but their effects on variability are yet to be investigated. The aim of the present study was to assess the effects of vitamin E, vitamin C and polyphenols on the rate of daytime and night-time ambulatory BP variation. To assess these effects, two randomised, double-blind, placebo-controlled trials were performed. In the first trial (vitamin E), fifty-eight individuals with type 2 diabetes were given 500mg/d of RRR-α-tocopherol, 500mg/d of mixed tocopherols or placebo for 6 weeks. In the second trial (vitamin C-polyphenols), sixty-nine treated hypertensive individuals were given 500mg/d of vitamin C, 1000mg/d of grape-seed polyphenols, both vitamin C and polyphenols, or neither (placebo) for 6 weeks. At baseline and at the end of the 6-week intervention, 24h ambulatory BP and rate of measurement-to-measurement BP variation were assessed. Compared with placebo, treatment with α-tocopherol, mixed tocopherols, vitamin C and polyphenols did not significantly alter the rate of daytime or night-time systolic BP, diastolic BP or pulse pressure variation (P>0·05). Treatment with the vitamin C and polyphenol combination resulted in higher BP variation: the rate of night-time systolic BP variation (P=0·022) and pulse pressure variation (P=0·0036) were higher and the rate of daytime systolic BP variation was higher (P=0·056). Vitamin E, vitamin C or grape-seed polyphenols did not significantly alter the rate of BP variation. However, the increase in the rate of BP variation suggests that the combination of high doses of vitamin C and polyphenols could be detrimental to treated hypertensive individuals.

Mass spectrometry quantitation and analysis of urinary metabolites of grape seed extract polyphenols in a rat model of menopause (1025.11)

Differences in urinary biomolecules following ovariectomy, and the impact of dietary polyphenols (grapeseed extract [GSE]) in rodents were examined by nanoLC‐tandem mass spectrometry, and the impact of dietary polyphenols (grapeseed extract [GSE]). Urines from sham‐ovariectomy (OVX) and ovariectomized ((OVX) rats were analyzed, where both groups were given GSE, thus, any differences were due to the OVX. In positive mode LC‐MS/MS, 5,589 peaks were resolved with unique retention times. Of these, 12% were significantly different in abundance (p&lt;0.05), with 2% of this subgroup (p&lt;0.001). Conclusive identification of significant peaks required both the METLIN software on the Scripps XCMS server (Tautenhahn et al., Anal. Chem, 2012) and the Human Metabolome Database (Wishart et al., Nucleic Acids Res, 2007). Experiments are ongoing to continue identification of peaks using MS/MS, as well as to populate the appropriate databases with conjugated forms of polyphenols to enable deeper analysis. In TARGETED metabolomics analysis, we determined that glucuronidated grapeseed polyphenols were increased in the urines of OVX rats, indicating that OVX increased the amount or activity of the relevant glucuronosyltransferases. This is the first metabolomics analysis of urinary biomolecules in a model of menopause, and of effects and fate of dietary polyphenols.Grant Funding Source: NIH/NCCAM R21‐AT00480531

Absorption enhancement of grape seed polyphenols by complexation with phosphatidyl choline

Grape seed polyphenols (GPP) are reported to have various biological effects along with strong antioxidant potential. Pharmacokinetic studies of GPP reveal its poor absorption through the intestine. The objective of the present study was to enhance bioavailability of GPP by its complexation with phosphatidyl choline. A complex of GPP was prepared with phosphatidyl choline and characterized on the basis of solubility, melting point, DSC, and IR. Everted intestine sac technique was used to study ex vivo drug absorption of GPP-PC complex and plain GPP. Pharmacokinetic studies were performed in rats and the hepatoprotective activity of GPP-PC complex was also compared with GPP and GPP-PC physical mixture in isolated rat hepatocytes. Analytical reports along with spectroscopic data revealed the formation of the complex. The results of ex vivo study show that the GPP-PC complex has significantly increased absorption compared with GPP, when given in equimolar doses. The complex showed enhanced bioavailability, improved pharmacokinetics, and increased hepatoprotective activity as compared to GPP or GPP-PC physical mixtures. Enhanced bioavailability of GPP-PC complex may be due to the amphiphilic nature of the complex, which greatly enhance the lipid miscibility of GPP. The present study clearly indicates the superiority of complex over GPP, in terms of better absorption, enhanced bioavailability, and improved pharmacokinetics.

Grape Seed Polyphenols Protect Cardiac Cells from Apoptosis via Induction of Endogenous Antioxidant Enzymes

Grape seed extract (GSE) has been reported to exert protective effects on various forms of cardiac disorders. The cardiovascular protective effects of GSE are believed to be ascribed to its antioxidative properties. A series of studies have demonstrated that polyphenols are instrumental for the antioxidative properties of GSE. This study was undertaken to investigate whether two major polyphenols isolated from GSE (catechin and proanthocyanidin B4) could increase the endogenous antioxidant enzymes in cardiomyocytes, and whether such increased cellular defenses could provide protection against oxidative cardiac cell injury. Incubation of cardiac H9C2 cells with micromolar concentrations of catechin or proanthocyanidin B4 resulted in a significant induction of cellular antioxidant enzymes in a concentration-dependent fashion. Furthermore, catechine or proanthocyanidin B4 pretreatment led to a marked reduction in xanthine oxidase (XO)/xanthine-induced intracellular reactive oxygen species (ROS) accumulation and cardiac cell apoptosis. These results indicated that grape seed polyphenols (GSP) could protect against cardiac cell apoptosis via the induction of endogenous antioxidant enzymes. This may be an important mechanism underlying the protective effects of GSE observed with various forms of cardiovascular disorders.

Protective Effect of Grape Seed Polyphenols against High Glucose-Induced Oxidative Stress

We aimed to clarify whether grape seed polyphenols (GSPs) are candidates therapeutic agents against diabetes mellitus, and to determine what degree of GSP oligomerization has the most potent efficacy. We studied the protective effects of various molecular weight GSPs (monomer, oligomer, polymer, and oligonol) on high glucose-induced cytotoxicity. In the present study, a high concentration of glucose (30 mM) induced cytotoxicity and oxidative stress (reactive oxygen species and nitric oxide) in cultured LLC-PK1 cells, but treatment with GSPs, especially oligomer GSPs, had potent protective effects against high glucose-induced oxidative stress. In addition, high glucose induced nuclear translocation of nuclear factor-kappa B, and increased expression of cyclooxygenase-2, inducible nitric oxide synthase, and bax, but GSP treatment inhibited them. These results indicate that GSPs have protective effects against high glucose-induced cytotoxicity, and among them, oligomer GSPs have more potent effects than other GSPs (monomer, polymer, and oligonol) on high glucose-induced renal cell damage.

The combination of vitamin C and grape-seed polyphenols increases blood pressure: a randomized, double-blind, placebo-controlled trial

There is growing evidence that oxidative stress contributes to the pathogenesis of hypertension and endothelial dysfunction. Thus, dietary antioxidants may beneficially influence blood pressure (BP) and endothelial function by reducing oxidative stress. To determine if vitamin C and polyphenols, alone or in combination, can lower BP, improve endothelial function and reduce oxidative stress in hypertensive individuals. A total of 69 treated hypertensive individuals with a mean 24-h ambulatory systolic blood pressure > or = 125 mmHg participated in a randomized, double-blind, placebo-controlled, factorial trial. Following a 3-week washout, participants received 500 mg/day vitamin C, 1000 mg/day grape-seed polyphenols, both vitamin C and polyphenols, or neither for 6 weeks. At baseline and post-intervention, 24-h ambulatory BP, ultrasound-assessed endothelium-dependent and -independent vasodilation of the brachial artery, and markers of oxidative damage, (plasma and urinary F2-isoprostanes, oxidized low-density lipoproteins and plasma tocopherols), were measured. A significant interaction between grape-seed and vitamin C treatments for effects on BP was observed. Vitamin C alone reduced systolic BP versus placebo (-1.8 +/- 0.8 mmHg, P = 0.03), while polyphenols did not (-1.3 +/- 0.8 mmHg, P = 0.12). However, treatment with the combination of vitamin C and polyphenols increased systolic BP (4.8 +/- 0.9 mmHg versus placebo; 6.6 +/- 0.8 mmHg versus vitamin C; 6.1 +/- 0.9 mmHg versus polyphenols mmHg, each P < 0.0001) and diastolic BP (2.7 +/- 0.6 mmHg, P < 0.0001 versus placebo; 1.5 +/- 0.6 mmHg, P = 0.016 versus vitamin C; 3.2 +/- 0.7 mmHg, P < 0.0001 versus polyphenols). Endothelium-dependent and -independent vasodilation, and markers of oxidative damage were not significantly altered. Although the mechanism remains to be elucidated, these results suggest caution for hypertensive subjects taking supplements containing combinations of vitamin C and polyphenols.

Protective Effects of Oligomers of Grape Seed Polyphenols Against β‐Amyloid‐Induced Oxidative Cell Death

beta-Amyloid (Abeta) is considered to be responsible for the formation of senile plaques that accumulate in the brains of patients with Alzheimer's disease (AD). There is compelling evidence supporting the notion that Abeta-induced cytotoxicity is mediated through the generation of reactive oxygen species (ROS). Recently, considerable attention has been focused on a wide array of non-vitamin antioxidants present in edible plants that are able to scavenge ROS, thereby protecting against oxidative damage. In this study, we have investigated the possible protective effects of formulated polyphenol oligomers (Oligonol) derived from grape seed extracts on Abeta-induced oxidative cell death. Rat pheochromocytoma (PC12) cells treated with Abeta exhibited increased accumulation of intracellular ROS and underwent apoptosis, as determined by positive in situ terminal end labeling, decreased mitochondrial membrane potential, and the cleavage of poly(ADP-ribose)polymerase. Oligonal attenuated Abeta-induced cytotoxicity, apoptotic features, intracellular ROS accumulation, and lipid peroxidation and increased the cellular glutathione pool. Moreover, Abeta transiently induced the activation of nuclear factor kappaB in PC12 cells, which was suppressed by pretreatment with Oligonol.

Effects of Grape Seed Polyphenols on Serum and Hepatic Lipid Contents and Fecal Steroid Excretion in Normal and Hypercholesterolemic Rats.

The effects of grape seed polyphenol (GSP) administered orally at doses of 0.01-1.0 g/kg per day to normal and hypercholesterolemic rats for 28 and 36 days, respectively, was evaluated by measuring changes both in the concentrations of serum and hepatic lipids and in fecal steroid excretion. Body weight gain decreased dose-dependently both in normal and hypercholesterolemic rats. Relative weight of the liver was significantly lower in normal rats given more than 0.2 g/kg GSP compared with control rats. Compared with control groups, relative weight of the liver was significantly lower in normal rats given more than 0.2 g/kg GSP, and in hypercholesterolemic rats given more than 0.1 g/kg GSP, respectively. In hypercholesterolemic rats, food or calorie intake was significantly lower in rats given more than 0.1 g/kg GSP than in control rats. Dose-dependency was observed in serum concentrations of serum triglycerides and thiobarbituric acid reactive substances and the content of hepatic phospholipids in normal rats, and in serum concentration and hepatic content of triglycerides in hypercholesterolemic rats. A significant increase in fecal excretions of neutral steroids and bile acids was found in normal rats given a dose of 1.0 g/kg GSP. Dose-dependent decrease of 12-keto lithocholic acid and increase of lithocholic acid were also observed. By contrast, there was no significant change in fecal excretions of neutral steroids and bile acids in hypercholesterolemic rats. Thus, GSP seems to affect lipid metabolism in rats by lowering the concentrations of serum and hepatic triglycerides rather than by altering the metabolism of cholesterol.