Grape Seed extract

The Effect of Supplementation of Grape Seed Proanthocyanidin Extract on Vascular Dysfunction in Experimental Diabetes.
Okudan N, Barışkaner H, Gökbel H, Sahin AS, Belviranlı M, Baysal H.
J Med Food. 2011 Jun 11

 Abstract Increased oxidative stress and impaired endothelium-dependent relaxation could underlie many of the vascular complications associated with diabetes. We aimed to investigate the effect of supplementation with grape seed proanthocyanidin extract (GSPE), a natural antioxidant, on vascular responses and oxidative stress in streptozotocin-induced diabetic rats. Male Sprague-Dawley rats were divided into three groups: control rats, untreated diabetic rats, and GSPE (100 mg/kg, for 6 weeks)-supplemented diabetic rats. Thoracic aorta rings of the rats were mounted in organ baths, and relaxant responses to acetylcholine (ACh), A23187, and sodium nitroprusside (SNP) were assayed in tissues precontracted with 60 mM KCl. Plasma samples used for the measurement of malondialdehyde (MDA) level and superoxide dismutase (SOD) activity. The endothelium-dependent relaxations in response to ACh and A23187 were impaired, but endothelium-independent relaxation in response to SNP did not change in diabetic rats. Supplementation with GSPE significantly improved the relaxant responses to ACh and A23187. The MDA level was significantly elevated and the plasma SOD activity was decreased in diabetic rats, but supplementation with GSPE attenuated the elevated MDA levels and increased plasma SOD activity. Thus supplementation of GSPE may attenuate oxidative stress through the inhibition of lipid peroxidation and may restore endothelial function and reduce the risk of vascular disease in diabetes. PMID: 21663473

  Grape seed extract for control of human enteric viruses.
Su X, D’Souza DH.
Appl Environ Microbiol. 2011 Jun;77(12):3982-7

 Grape seed extract (GSE) is reported to have many pharmacological benefits, including antioxidant, anti-inflammatory, anticarcinogenic, and antimicrobial properties. However, the effect of this inexpensive rich source of natural phenolic compounds on human enteric viruses has not been well documented. In the present study, the effect of commercial GSE, Gravinol-S, on the infectivity of human enteric virus surrogates (feline calicivirus, FCV-F9; murine norovirus, MNV-1; and bacteriophage MS2) and hepatitis A virus (HAV; strain HM175) was evaluated. GSE at concentrations of 0.5, 1, and 2 mg/ml was individually mixed with equal volumes of each virus at titers of ∼7 log(10) PFU/ml or ∼5 log(10) PFU/ml and incubated for 2 h at room temperature or 37°C. The infectivity of the recovered viruses after triplicate treatments was evaluated by standardized plaque assays. At high titers (∼7 log(10) PFU/ml), FCV-F9 was significantly reduced by 3.64, 4.10, and 4.61 log(10) PFU/ml; MNV-1 by 0.82, 1.35, and 1.73 log(10) PFU/ml; MS2 by 1.13, 1.43, and 1.60 log(10) PFU/ml; and HAV by 1.81, 2.66, and 3.20 log(10) PFU/ml after treatment at 37°C with 0.25, 0.50, and 1 mg/ml GSE, respectively (P < 0.05) in a dose-dependent manner. GSE treatment of low titers (∼5 log(10) PFU/ml) at 37°C also showed viral reductions. Room-temperature treatments with GSE caused significant reduction of the four viruses, with higher reduction for low-titer FCV-F9, MNV-1, and HAV compared to high titers. Our results indicate that GSE shows promise for application in the food industry as an inexpensive novel natural alternative to reduce viral contamination and enhance food safety. PMID: 21498749

  Protective effects of grape seed procyanidin extract against nickel sulfate-induced apoptosis and oxidative stress in rat testes.
Su L, Deng Y, Zhang Y, Li C, Zhang R, Sun Y, Zhang K, Li J, Yao S.
Toxicol Mech Methods. 2011 Jul;21(6):487-94.

 This study determined whether nickel sulfate (Ni)-induced reproductive damage occurs via apoptosis and oxidative stress and to examine the expression of Bax and c-kit and their effects on Ni exposure. The study also explored the protective effects of grape seed proanthocyanidin extract (GSPE) against Ni toxicity in the testes. Wistar rats were treated with normal saline, Ni alone (1.25, 2.5, and 5 mg/kg/day), and Ni (2.5 mg/kg/day) plus GSPE (50 and 100 mg/kg/day). After 30 days, Ni significantly decreased sperm motility and the percentage of S-phase cells and enhanced testicular apoptosis in the 2.5 and 5 mg groups. The levels of malondialdehyde (MDA), hydrogen peroxide (H(2)O(2)), and nitric oxide (NO) significantly increased. The decreased activity of glutathione peroxidase and catalase in the Ni groups showed that Ni could increase oxidative stress, especially at 2.5 and 5 mg. Western blot analysis showed that the expression of Bax protein and c-kit increased in 2.5 and 5 mg Ni groups compared with controls. Conversely, these changes were partially attenuated in rats simultaneously administered GSPE, especially in the 100 mg group. These results demonstrate the following: (1) Ni exhibits reproductive toxicity in rats by decreasing sperm at concentrations of 2.5 and 5 mg; (2) intratesticular apoptosis, oxidative stress, and c-kit overexpression play pivotal roles in reproductive damage induced by Ni; and (3) GSPE enhances sperm motility by down-regulating c-kit expression and offsetting the apoptosis and oxidative stress induced by Ni by directly decreasing MDA and NO, scavenging H(2)O(2), and down-regulating Bax expression. PMID: 21417627

  Acute administration of grape seed proanthocyanidin extract modulates energetic metabolism in skeletal muscle and BAT mitochondria.
Pajuelo D, Díaz S, Quesada H, Fernández-Iglesias A, Mulero M, Arola-Arnal A, Salvadó MJ, Bladé C, Arola L.
J Agric Food Chem. 2011 Apr 27;59(8):4279-87

 Proanthocyanidin consumption might reduce the risk of developing several pathologies, such as inflammation, oxidative stress and cardiovascular diseases. The beneficial effects of proanthocyanidins are attributed to their antioxidant properties, although they also can modulate gene expression at the transcriptional level. Little is known about the effect of proanthocyanidins on mitochondrial function and energy metabolism. In this context, the objective of this study was to determine the effect of an acute administration of grape seed proanthocyanidin extract (GSPE) on mitochondrial function and energy metabolism. To examine this effect, male Wistar rats fasted for fourteen hours, and then they were orally administered lard oil containing GSPE or were administered lard oil only. Liver, muscle and brown adipose tissue (BAT) were used to study enzymatic activity and gene expression of proteins related to energetic metabolism. Moreover, the gastrocnemius muscle and BAT mitochondria were used to perform high-resolution respirometry. The results showed that, after 5 h, the GSPE administration significantly lowers plasma triglycerides, free fatty acids, glycerol and urea concentrations. In skeletal muscle, GSPE lowers FATP1 mRNA levels and increases mitochondrial oxygen consumption, using pyruvate as the substrate, suggesting a promotion of glycosidic metabolism. Furthermore, GSPE increased the genetic expression of key genes in energy metabolism such as peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC1α), and modulated the enzyme activity of proteins, which are involved in the citric acid cycle and electron transport chain (ETC) in BAT. In conclusion, GSPE affects mainly the skeletal muscle and BAT mitochondria, increasing their oxidative capacity rapidly after acute supplementation. PMID: 21401106

  Grape seed proanthocyanidin extract protects human lens epithelial cells from oxidative stress via reducing NF-кB and MAPK protein expression.
Jia Z, Song Z, Zhao Y, Wang X, Liu P.
Mol Vis. 2011 Jan 20;17:210-7.

 Oxidative damage induced by H₂O₂ treatment can irreversibly damage the lens epithelium, resulting in cell death and cataract. Grape seed extract (GSE) is a widely consumed dietary supplement that has the capability to scavenge oxidants and free radicals. GSE contain 70%-95% standardized proanthocyanidins. The study described herein investigated the protective effect of Grape seed proanthocyanidin extract (GSPE) on H₂O₂-induced oxidative stress in human lens epithelial B-3 (HLEB-3) cells and the possible molecular mechanism involved. HLE-B3 cells exposed to different doses of H₂O₂ were cultured with various concentrations of GSPE and subsequently monitored for cell viability by the 4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT) assay. The apoptosis rate and ROS generation were detected by flow cytometric analysis. Expression of NF-кB/P65 and mitogen activated protein kinase (MAPK) proteins were measured by western blot. GSPE clearly reduced H₂O₂ induced cell apoptosis and reactive oxygen species (ROS) generation and protected HLEB-3 cells from H₂O₂ induced oxidative damage. GSPE depressed H₂O₂-induced activation and translocation of NF-кB/p65. GSPE also depressed H₂O₂-induced phosphorylation of the p38 and c-Jun N-terminal kinase (JNK) proteins of the MAPK family at various time points studied. GSPE could be useful in attenuation of H₂O₂-induced oxidative stress and the activation of NF-кB and MAPK signaling in HLE-B3 cells, which suggests that GSPE has a potential protective effect against cataractogenesis. PMID: 21264233

 Grape seed extract alleviates high-fat diet-induced obesity and heart dysfunction by preventing cardiac siderosis.
Charradi K, Sebai H, Elkahoui S, Ben Hassine F, Limam F, Aouani E.
Cardiovasc Toxicol. 2011 Mar;11(1):28-37.

 Obesity is a tremendous public health problem, characterized by ectopic accumulation of fat into non-adipose tissues, leading to oxidative stress and chronic inflammation, in which the heart is the most severely affected organ. We used an experimental model of high-fat-diet (HFD)-induced obesity to analyze the link between oxidative stress and heart dysfunction. We also studied the cardioprotective effect of a grape seed and skin extract (GSE). Exposure of rats to HFD during 45 days induced heart hypertrophy, inflammation as assessed by plasma CRP elevation and contractile dysfunction as revealed after ischemia/reperfusion of Langendorff-perfused hearts. HFD also induced cardiac steatosis and lipotoxicity, which are linked to an oxidative stress status, worsened by increased siderosis and resulting in Ca(2+) overload. Importantly, GSE alleviated all the deleterious effects of HFD treatment. These studies suggest that GSE is a safe anti-obesity and cardioprotective agent that should also find potential applications in other inflammatory damaging conditions as stroke. PMID: 21234706

  Protective effect of grape seed extract on gentamicin-induced acute kidney injury.
Safa J, Argani H, Bastani B, Nezami N, Rahimi Ardebili B, Ghorbanihaghjo A, Kalagheichi H, Amirfirouzi A, Mesgari M, Soleimany Rad J.
Iran J Kidney Dis. 2010 Oct;4(4):285-91.

 This study was designed to determine the protective effect of red grape seed extract (RGSE) on gentamicin-induced nephrotoxicity in rats. Thirty male Wistar rats were divided into 3 groups to receive RGSE, for 60 days followed by intraperitoneal injection of saline solution (as placebo) for 8 days (group 1); RGSE followed by gentamicin for 8 days (group 2); and gentamicin without pre-medication of RGSE (group 3). Oral RGSE, 40 mg/kg/d, and intraperitoneal injection of gentamicin, 100 mg/kg/d, were administered in these groups of rats. Blood and urine samples were collected on days 0 and 68 of the study. Then, the kidneys were removed for pathologic examination. On day 68, serum creatinine and blood urea nitrogen concentrations were highest in group 3, which was significantly higher than in group 1 (P = .001 and P = .004, respectively), while slightly higher than in group 2 (P = .30 and P = .50, respectively). Fractional excretion of sodium was not significantly different between the three groups. Histopathological evaluation showed that rats in group 3 had significantly higher degrees of severe acute tubular necrosis and interstitial mononuclear cell infiltration than the rats in groups 1 and 2 (P < .001). This animal study suggests that pretreatment with RGSE protects against gentamicin-induced acute kidney injury as evident on tissue histology. However, this was not accompanied with significant improvement in biochemical markers of kidney injury. PMID: 20852368