The following section is information on OPC research related to grape seed extract. Some of the published research articles are selected for the 2 years of 2008-2010 and are critically summarized by our 3 PhD scientists in natural product and medicinal chemistry. All the writings are original and are based on our critical reading and understanding of the original scientific papers. All copyrights are reserved.
Disclaim: The following publications are about preliminary scientific studies of grape seed extract.
We do not claim any drug effects or therapeutic benefits for our FrenchGlory isotonic OPC products.
- Polyphenolic compounds for treating neurodegenerative disorders involving protein misfolding. Expert Rev Proteomics. 2010 Aug; 7(4): 579-89.
OPC grape seed extract as a dietary supplement is studied for neurodegenerative diseases, - the age-dependent intracellular formation of misfolded protein aggregates in the brain. There is not an effective drug intervention. Available drug treatments are limited to modest relief of disease symptoms and cannot stop or slow down the disease progression. OPC grape seed extract contain antioxidant polyphenols, which have been demonstrated the efficacy in vitro and in vivo in mitigating certain misfolded protein-mediated neuropathologic and clinical phenotypes. In this paper, the grape-seed polyphenolic extract OPCs are reviewed for their effects as antioxidant dietary supplement on neurodegenerative diseases, including Alzheimer's disease, Huntington's disease, Parkinson's disease and a number of tau-mediated disorders. There has been accumulating evidence implicating bioavailability of OPC grape seed extract components in the brain. The tolerability and safety of OPC grape seed extract are well established in animal models and in humans. All the available information supports that a variety of patients of neurodegenerative disorders involving misfolded protein-mediated neuropathologic mechanisms can benefit from supplement of OPC grape seed extract.
- Modulatory effect of grape-seed procyanidins on local and systemic inflammation in diet-induced obesity rats. J Nutr Biochem. 2010 Jul 22.
OPC grape seed extract (or grape-seed procyanidin extract as the authors called) is investigated for its antioxidant properties in improving local and systemic inflammation in diet-induced obesity rats. This OPC grape seed extract is analyzed in 2 different ways – preventive and corrective. 1, OPC grape seed extract (30 mg/kg a day) was used to feed rats of 60% kcal fat diet for 19 weeks. 2, Rats were induced cafeteria diet obesity for 13 weeks, and then OPC grape seed extract was tested for effect on the rat obesity by feeding OPC grape seed extract to 3 groups of rats in 0, 25 and 50 mg/kg, respectively, for 10 and 30 days. In the preventive study, OPC grape seed extract down-regulated 3 bio parameters: body weight, plasmatic systemic markers of inflammation tumor necrosis factor-alpha (TNF-alpha) and C-reactive protein (CRP). OPC grape seed extract increased adiponectin expression, and decreased TNF-alpha, interleukin-6 and CRP expression in mesenteric white adipose tissue and muscle TNF-alpha. The low expression rates of hepatic inflammatory markers caused by OPC grape seed extract resulted in reduction of liver NF-kappaB activity. The OPC grape seed extract dietary supplementation reduced expression of Emr1 (specific marker of macrophage F4/80), and reduced macrophage infiltration of NF-kappaB activity. The corrective study showed only the high dose of OPC grape seed extract reduced CRP plasma levels in the short treatment without changes in plasmatic TNF-alpha. OPC grape seed extract helps preventing imbalanced obesity cytokine pattern. No conclusion could be made about its corrective effects. The OPC grape seed extract antioxidant might help prevent low-grade inflammatory-related diseases.
- Grape seed extract to improve liver function in patients with nonalcoholic fatty liver change. Saudi J Gastroenterol. 2010 Jul-Sep; 16(3):194-7.
Antioxidants have been shown supplemental benefits by animal models in nonalcoholic fatty liver disease, while available therapeutic drug interventions have limited efficacy. OPC grape seed extract belongs to this class of antioxidants and a polyphenolic dietary supplement. Therapeutic effects of OPC grape seed extract were evaluated using 3 groups of people in comparison to vitamin C in a double-blind setting. Each group has 15 patients. Patients enrolled in this efficacy study of OPC grape seed extract were followed up by the same evaluation repeated in 1st, 2nd and 3rd months. The mean age and standard deviation was 43.2 +/- 10.3 years. The OPC grape seed extract exhibited 3 significantly beneficial effects. 1, OPC grape seed extract improved the grade of fatty liver change. 2, OPC grape seed extract decreased alanine aminotransferase; 3, OPC grape seed extract improved fatty liver disease from the initial grade of steatosis more than vitamin C. Therefore, OPC grape seed extract exhibited supplemental benefits in 3 months investigation in patients with nonalcoholic fatty liver disease. The antioxidant OPC as dietary supplement may be more beneficial with a longer period of follow-up after 3 months.
- Incorporation and interaction of grape seed extract in membranes and relation with efficacy in muscle foods. J Agric Food Chem. 2010 Jul 28; 58(14): 8365-74.
OPC grape seed extract as an antioxidant exhibits inhibitory activity against lipid oxidation of fish mince. OPC grape seed extract is studied for the interaction and location of phenolic antioxidants in model membranes with the aim to identify mechanisms involved in the antioxidant effectiveness in muscle foods. The OPC grape seed extract and its 3 components, catechin, epicatechin and procyanidin B(2) are located and induce changes in phospholipid model membranes. Their effects were studied by different biophysical techniques and related to their antioxidant efficiency. OPC grape seed extract prevent oxidation the most effectively in chilled minced fish muscle. The antioxidant efficiency found in fish muscle is not correlated well with in vitro antioxidant capacities of OPC grape seed extract and the 3 individual components - catechin, epicatechin and procyanidin B(2). Procyanidin B(2) was found in a more internal location than monomeric catechin and epicatechin within the phospholipid palisade, as indicated by the phospholipid/water partition coefficients and fluorescence quenching. Fluorescence anisotropy results indicated that OPC grape seed extract exhibited stronger effect than any of the 3 individual components - catechin, epicatechin and procyanidin B(2) in the increase of the lipid order at the DMPC fluid phase. Dehydration in DMPC membranes at the phospholipid/water interface was observed only with OPC grape seed extract, causing resistance to solubilization by nonionic detergents in DMPC membranes. Hydrogen bonding between procyanidins and the polar head groups of the phospholipids may account for the dehydration of OPC grape seed extract at the phospholipid/water interface and membrane-stabilization. Overall, OPC grape seed extract as a whole is demonstrated stronger antioxidant effects than any of the 3 individual components in inhibition of lipid oxidation in fish muscle, possibly by preventing radical propagation and/or scavenging oxidizing free radicals.
- Lipogenesis is decreased by grape seed proanthocyanidins according to liver proteomics of rats fed a high fat diet. Mol Cell Proteomics. 2010 Jul; 9(7):1499-513.
OPC grape seed extract contains bioactive proanthocyanidins and related flavonoids of health-beneficial effects on metabolic syndrome, type 2 diabetes, and cardiovascular disease. Grape seed proanthocyanidin extract – OPC was studied using 3 groups of rats, which were fed over a period of 13 weeks. Rats in Group 1 is a control group of a chow diet without OPC grape seed extract; Rats in Group 2 were fed a high fat diet without supplementation of OPC; Group 3 were fed both a high fat diet and OPC grape seed extract for the last 10 days. A Triton X-114-based two-phase separation technology was used to fraction the liver proteome, resulting in soluble and membrane protein fractions. This technology significantly improved the total proteome coverage. 90 Proteins were found to have a significant (p < 0.05) minimal expression difference of 20% in metabolic syndrome rats (Group 2) without supplementation of OPC grape seed extract. In Group 3, only 75 proteins had a minimal expression difference of 20%. It was reported earlier that OPC grape seed extract corrected dyslipidemia developed due to a high-fat diet feeding and down-regulated genes controlling lipogenesis and VLDL assembling in liver. This correction of dyslipidemia by OPC grape seed extract was attributed to the repression of hepatic lipogenesis. Data from the current study support those findings, and reveal an extensive list of proteins associated with the induction of hepatic glycogenesis, glycolysis, and fatty acid and triglyceride syntheses caused by high fat diet feeding. The pattern of corrective effects was observed to a large extent due to supplementation of OPC grape seed extract in Group 3 with a wider effect than previously thought. This study also reveals more possible targets associated with the correction of the metabolic syndrome by OPC grape seed extract. Further, this study provides new fundamental understanding of a list of novel candidate proteins, which may be useful as drug discovery targets in the treatment of metabolic syndrome.
- Folate targeted polymeric 'green' nanotherapy for cancer. Nanotechnology. 2010 Jul 16; 21(28): 285107.
OPC grape seed extract is encapsulated using poly (lactide-co-glycolide) (PLGA) nanoparticles in order to enhance the phytochemical supplement efficacy. OPC grape seed extract is made as ‘Nano-GSE’ or ‘Nano-OPC’ prepared by a nanoprecipitation technique. The OPC-loaded nanoparticles of size approximately 100 nm is demonstrated to have a high colloidal stability at physiological pH. Folate receptor over-expressing cancers are targeted by in vitro conjugation of this Nano-OPC with a potential cancer targeting ligand, folic acid. This folic acid conjugated Nano-OPC exhibited highly specific cellular uptake on folate receptor positive cancer cells, as shown by data from fluorescence microscopy and flow cytometry. The efficiency of targeted (FA conjugated) nanoformulations is compared with that of non-targeted (non-FA conjugated) in causing cancer cell death. The IC50 values of free Nano-OPC grape seed extract is approximately 3-folds higher that that of FA-Nano-OPC conjugate. Therefore, the bioavailability of FA-Nano-OPC conjugate for cancer cells is largely improved, as compared to the non-targeted Nano-OPC. The apoptotic index is substantially elevated by the receptor-targeting FA-Nano-OPC conjugate. In conclusion, nanoparticle-mediated delivery of anticancer polyphenols can enhance bioavailability and effectively target cancer by a so-called 'green' approach.
- Development of a grape seed polyphenolic extract with anti-oligomeric activity as a novel treatment in progressive supranuclear palsy and other tauopathies. J Neurochem. 2010 Sep;114(6):1557-68.
OPC grape seed extract was earlier demonstrated to effectively prevent neurotoxic aggregates of tau fibrillization and therapeutically cause the dissociation of preformed tau aggregates [J. Alzheimer's Dis. (2009) vol. 16, pp. 433]. Safety, bioavailability, bioactivity and functional preclinical studies of OPC grape seed extract were also well studied in laboratory animals and in humans. In the current article, the studies of OPC grape seed extract antioxidant are reviewed as dietary supplement for tauopathies - a diverse group of neurodegenerative diseases - including progressive supranuclear palsy (PSP), corticobasal degeneration and Alzheimer's disease, etc.. These neurodegenerative diseases are characterized by progressive, age-dependent intracellular formation of misfolded protein aggregates. OPC grape seed extract is potentially a novel phytomedicine for the treatment of certain forms of tauopathies including PSP. The biochemical characterization of OPC grape seed extract and its potential preventative and therapeutic roles are discussed in model systems of neurodegenerative diseases.
- Dietary-feeding of grape seed extract prevents azoxymethane-induced colonic aberrant crypt foci formation in fischer 344 rats. Carcinog. 2010 Jul; 49(7): 641-52.
OPC and related polyphenolic bioflavonoids have emerged as very valuable dietary supplements as a novel approach in chemoprevention of various malignancies, including colorectal cancer. In this study, an OPC grape seed extract is investigated for its effectiveness in preventing azoxymethane-induced aberrant crypt foci (ACF) formation in Fischer 3-4-4 rats. The OPC grape seed extract is studied using 3 groups of rats. All the 3 groups of rats are injected with azoxymethane at the age of 6 weeks. Group 1 rats are fed control diet, Group 2 rats are fed OPC grape seed extract of 0.25% by weight, and Group 3 are fed OPC grape seed extract of 0.5% by weight, in pre- and post- azoxymethane or only post-azoxymethane experimental protocols. 10 Weeks later after the azoxymethane feeding, rats are sacrificed and colon ACF formation is assessed. In the meanwhile, cell proliferation, apoptosis, and molecular analyses are conducted by immunohistochemistry. The supplement of OPC grape seed extract antioxidant protects the rats against azoxymethane -induced ACF formation. The OPC grape seed extract reduces the number of ACF by up to 60% (P < 0.001) and reduces crypt multiplicity by 66% (P < 0.001). The OPC grape seed extract inhibits azoxymethane -induced cell proliferation, and stimulates apoptosis in colon including ACF. OPC grape seed extract also decreases the levels of cyclin D1, COX-2, iNOS and survivin. This OPC supplement suppresses azoxymethane-induced increase of the levels of beta-catenin and NF-kappaB in colon tissues. This study demonstrates the chemopreventive effect of OPC grape seed extract against the early development and progression of colon carcinogenesis in rats. The supplementation of antioxidant polyphenol grape seed extract may affect beta-catenin and NF-kappaB signaling, and may have the preventive effect on human CRC.
- Grape seed extract inhibits the growth and pathogenicity of Staphylococcus aureus by interfering with dihydrofolate reductase activity and folate-mediated one-carbon metabolism. Int J Food Microbiol. Jun 30;141 (1-2):17-27
OPC grape seed extract, a natural food product rich in polyphenol antioxidants, was demonstrated the activity to inhibit dihydrofolate reductase and growth of S. aureus, which is among the 3 most common pathogens that cause infectious and food borne diseases worldwide. OPC grape seed extract was found to reduce the intracellular content of tetrahydrofolate, the major folate species identified in S. aureus. The growth inhibition by OPC grape seed extract was offset by adding 3 different materials: tetrahydrofolate, 5,10-methylenetetrahydrofolate or methionine to the medium. The differential rescuing effects elicited by thymidine and methionine indicated that the impact of OPC grape seed extract in folate-mediated one-carbon metabolism is more significant on methionine cycle than on thymidine monophosphate synthesis. Zebrafish exhibited significantly reduced inflammatory responses and mortality when zebrafish was infected with S. aureus pre-incubated with OPC grape seed extract. OPC grape seed extract may be useful in the control of S. aureus-induced food poisoning.
- Procyanidin oligomers (OPC) of grape-seed extract activate the insulin receptor and key targets of the insulin signaling pathway differently from insulin. Journal of Nutritional Biochemistry. June 2010; 21(6): 476-481.
Earlier studies showed that oligomeric procyanidins (OPCs) can suppress hyperglycaemia in streptozotocin-diabetic rats and OPCs stimulate glucose uptake in insulin-sensitive cell lines. In the current study, grape seed extract OPCs were studied for possible mechanisms of stimulating the uptake of glucose, as OPCs may interact with signal transduction pathways. The questions are whether and how grape seed extract OPCs induce the autophosphorylation of the insulin receptor. This study showed that OPC treatment led to down-steam phosphorylation of protein kinase B at Thr-308, while insulin-induced the phosphorylation at much up-steam. The grape seed extract OPC phosphorylates Akt at Ser473, similar to what insulin does. Further, p44/p42 and p38 mitogen-associated protein kinases are phosphorylated at much higher extents induced by the grape seed extract OPCs than by insulin. Therefore, the grape seed extract OPCs interact with the signaling pathways by activating Akt and MAPK proteins. The differences between grape seed extract OPCs and insulin provide us the insight for us to understand the mechanism how OPCs exert a wide range of biological effects as a dietary supplement.
- Grape seed extract prevents azathioprine toxicity in rats. Phytother Res. 2010 Nov;24(11):1710-5.
OPC grape seed extract is studied for its effects on the azathioprine toxicity in rats. Azathioprine, a commonly used drug for autoimmune system disorders, induces hepatotoxicity and related side effects that limit its use. The effect of OPC grape seed extract on azathioprine toxicity was studied as compared to that of folic acid using 3 groups of rats (Group 1, control; Group 2, OPC; Group 3, folic acid). OPC grape seed extract or folic acid was daily applied by gavage simultaneously with azathioprine for 4 weeks. Some hematological parameters and liver histology were determined. The azathioprine treatment (25 mg/kg body weight) in Group 1 rats causes anemia, so that erythrocyte and leukocyte counts and reticulocyte and hematocrit percentages are decreased with the increased prothrombin time. Azathioprine also significantly suppresses phagocytic activity and lowers lymphocyte percentage. Azathioprine induced hepatic damage with pronounced changes in the histological structure and a number of related bio-parameters. Co-feeding of OPC grape seed extract and azathioprine in Group 2 largely reduces the azathioprine toxicities previously mentioned with improved bio-parameters. The significantly protected hepatic tissue may be contributed from the protection due to the antioxidant activity of OPC grape seed extract. In Group 3, folic acid co-administration with azathioprine showed only limited improvement of the anemia. The OPC grape seed extract is, therefore, significantly more effective in preventing oxidative damages, and exhibits potent protecting effect against azathioprine hepatotoxicity.
- PProtective Role of Grape Seed Extract against Doxorubicin-Induced Cardiotoxicity and Genotoxicity in Albino Mice. J Med Food. 2010 Jun 16.
Cardiotoxicity and genotoxicity of doxorubicin is a major problem for its large dose clinical uses in cancer treatments. Doxorubicin cardiotoxicity includes a dose-dependent decline in mitochondrial oxidative phosphorylation. In this study, OPC grape seed extract is evaluated for the possible protective effect as polyphenolic antioxidant against doxorubicin-induced toxicities in male Mus musculus var. albino mice. This study involves the micronucleus (MN) test in erythrocytes and the chromosome aberration (CA) test in bone marrow cells, and also involves measurement of levels of reduced glutathione (GSH) and lipid peroxidation as malondialdehyde in heart homogenates. The changes in heart histology are compared with and without the antioxidant supplement of OPC grape seed extract with 6 groups of mice. Group 1 is a blank control group with intraperitoneal injections of isotonic saline (0.02 mL/g) for 6 days. Group 2 is a doxorubicin control group with intraperitoneal injections of doxorubicin (2.5 mg/kg of body weight, six doses every other day; cumulative dosage, 15 mg/kg of body weight) for 6 days, without OPC grape seed extract. Group 3 rats are injected OPC grape seed extract (50 mg/kg of body weight, 21 doses every other day; cumulative dosage, 1,050 mg/kg of body weight) for 21 days. Group 4 rats are injected OPC grape seed extract (150 mg/kg of body weight, 21 doses every other day; cumulative dosage, 3,150 mg/kg of body weight) for 21 days. Rats in Group 5 are injected OPC grape seed extract (50 mg/kg of body weight, 28 doses every other day; cumulative dosage, 1,400 mg/kg of body weight) for 28 days plus doxorubicin (2.5 mg/kg of body weight, six doses every other day; cumulative dosage, 15 mg/kg of body weight) for 6 consecutive days. Rats in Group 6 are injected OPC grape seed extract (150 mg/kg of body weight, 28 doses every other day; cumulative dosage, 4,200 mg/kg of body weight) for 28 days plus doxorubicin (2.5 mg/kg of body weight, 6 doses every other day; cumulative dosage, 15 mg/kg of body weight) for 6 days. Doxorubicin caused heart damages and pronounced heart-histological changes. Doxorubicin significantly increases malondialdehyde content in the heart homogenate, and decreases the GSH level in Group 2. Doxorubicin increases the number of aberrant metaphases, MNs, and structural chromosomal aberrations such as chromatid breaks, dicentrics, acentric fragments, and gaps, the typical indications of genotoxicity. Doxorubicin exerts a detractive effect on the mitotic index of cells. Rats pretreated with OPC grape seed extract in Group 3, before treatment with doxorubicin, are significantly protected in their heart tissue by ameliorating the OPC antioxidant activity. In rats of Groups 4 and 5, OPC grape seed extract significantly suppressed the doxorubicin-induced increase of the malondialdehyde level in heart tissue, and rescued the doxorubicin-induced decrease of GSH level. OPC grape seed extract reduces the total aberrant metaphases and the frequency of structural CAs, significantly protecting bone marrow chromosomes from doxorubicin-induced genotoxicity. OPC grape seed extract leads to decreased frequency of MNs and increased mitotic index values. Therefore, OPC grape seed extract may be used as a dietary supplement, acting as a potent antioxidant in preventing heart damages and genotoxicity of bone marrow cells. Back to Top
- Apoptosis-inducing factor and caspase-dependent apoptotic pathways triggered by different grape seed extracts on human colon cancer cell line Caco-2. Br J Nutr. 2010 Jun 14: 1-9.
OPC grape seed extract of a variety of polyphenols has been established as safe dietary supplement and is widely used as antioxidant for antiaging and a variety of human health purposes. But the chemical composition of OPC grape seed extract from different grape cultivars differs greatly in flavan-3-ols content. The different extraction technologies may produce OPC ingredients of dramatically difference in the purity of OPC. 3 Different OPC grape seed extract ingredients from 3 manufacturers are evaluated in the current study on their effect and activity on human colon cancer cell line Caco-2. It is found that high doses of OPC grape seed extract from 3 different sources induced a significant but comparable inhibition on Caco-2 cell growth. The similar biological pathway is established for the 3 OPC grape seed extract ingredients of 3 different sources. The OPC extracts all caused enhanced apoptosis through both caspase-dependent and caspase-independent mechanisms. Each of the 3 OPC grape seed extracts of 3 different sources induces an early release of apoptosis-inducing factor and a dramatic increase in caspase 7 and caspase 3 activities. However, low and medium concentrations of the OPC grape seed extract (25 and 50 mug/mL) for the cancer cell treatment reveal significant difference in apoptotic rates induced by the 3 OPC grape seed extracts of 3 different sources. Back to Top
- Grape seed proanthocyanidins (OPC) attenuate vascular smooth muscle cell proliferation via blocking phosphatidylinositol 3-kinase-dependent signaling pathways. J Cell Physiol. June 2010, 223(3):713-26.
A grape seed extract OPC was investigated for effects on hyperproliferation of rat vascular smooth muscle cells (VSMCs) induced by high glucose (HG) in culture. The 3 factors of HG-induced rat VSMCs proliferation, ROS generation and NAPDH oxidase activity were found significantly inhibited by OPC grape seed extract. Phosphorylation and membrane translocation of Rac1, p47phox, and p67phox subunits leading to NADPH oxidase activation were caused by HG treatment, and were also remarkably disrupted by the treatment with OPC grape seed extract. OPC grape seed extract was able to suppress reactive oxygen species (ROS) generation and Rac1 activation, as indicated by the inhibition of HG-induced activation of ERK1/2, JNK1/2, PI3K/AKT/GSK3beta, and NF-kappaB signalings. The OPC grape seed extract blocked the HG-induced activation of PI-3 kinase subunit p110alpha, which is related to HG-induced cell proliferation and excess ROS production. Overall, OPC grape seed extract was able to suppress HG-induced VSMC growth through blocking PI-3 kinase-dependent signaling pathway, and may be used as a dietary supplement for people with retarding intimal hyperplasia and restenosis in diabetic vessels. Back to Top
- Amyloid-beta fibrillogenesis: structural insight and therapeutic intervention. Exp Neurol. Jun 2010; 223(2): 311-21.
Curcumin, (-)-epigallocatechin gallate (EGCG) and OPC grape seed extract, - the 3 polyphenol natural products are discussed as a part of this article for their effect to attenuate Abeta aggregation in treatment of Alzheimer disease. (-)-epigallocatechin gallate (EGCG) and OPC grape seed extract have been to inhibit amyloid production in transgenic mouse models of AD. These polyphenol natural products including OPC grape seed extract may be very valuable in amyloid-based therapeutics. The 3 polyphenols are discussed for their potential to slow the progression of AD by alleviating the deposition of Abeta.
- Grape seed extract enhances eNOS expression and NO production through regulating calcium-mediated AKT phosphorylation in H2O2-treated endothelium. Cell Biol Int. June 1, 2010.
An OPC grape seed extract was investigated for activity to stimulate endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) production in hydrogen peroxide-treated human umbilical vein endothelial cells (HUVEC). The eNOS expression and NO release in H2O2-treated cells were enhanced by the OPC grape seed extract in a concentration-dependent fashion. The confocal microscopy indicated that the intracellular ROS was inhibited and intracellular calcium was reduced by the OPC grape seed extract concentration-dependently in H2O2-treated cells. Pretreatments with OPC grape seed extract (2.0 mM), thapsigargin (2.0 mM), and 20.0 microM 2-aminoethoxydiphenyl borate (2-APB) instead of 0.25 microM extracellular calcium, led to significant inhibition of ROS. In a high extracellular calcium concentration of 13 mM, OPC grape seed extract stimulated in AKT phosphorylation, resulting in elevated eNOS expression and lowered ROS production. OPC grape seed extract inhibited InsP3Rs-mediated intracellular calcium excessive release and activated AKT phosphorylation in endothelial cells. Therefore, OPC grape seed extract protects HUVEC by H2O2-induced increases of eNOS and NO expression, and exhibits nutritional benefits for cardiovascular health and against atherosclerosis. Back to Top
- BBactericidal effect of grape seed extract on methicillin-resistant Staphylococcus aureus (MRSA). J Toxicol Sci. 2010; 35(3): 357-64.
OPC grape seed extract was investigated for antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) of 43 strains by gel diffusion, growth and respirometric studies. All MRSA strains exhibited sensitivity to OPC grape seed extract. All the 43 tested bacterial strains were completely inhibited by the OPC grape seed extract at a concentration of 3 mg/ml, equivalent to 20.7 microg/ml flavonoid content. OPC grape seed extract caused a disruption of the bacterial cell wall, resulting in bactericidal, as revealed by scanning and transmission electron microscopy. OPC grape seed extract of potent antioxidant polyphenolics exhibits antibacterial activity. OPC and related phenolic compounds in the grape seed extract were analyzed by Folin-Ciocalteu’s reagent. The commonly available OPC grape seed extract may, therefore, be used as a dietary supplement or a topical agent for MRSA diseases. Back to Top
- GGrape seed proanthocyanidins ameliorate Doxorubicin-induced cardiotoxicity. Am J Chin Med. 2010; 38(3): 569-84.
Doxorubicin is a natural product used in the treatment of a wide range of cancers, including hematological malignancies, many types of carcinoma, and soft tissue sarcomas. But high doses and cumulative uses of doxorubicin induce cardio toxicity, characterized by declining in mitochondrial oxidative phosphorylation. Doxorubicin-induced cardio toxicity may involve reactive oxygen species (ROS)-mediated oxidative stress. Antioxidant polyphenols such as OPC grape seed extract may be assessed for their effects in reducing oxidative stress and protecting against doxorubincin-induced cardio toxicity. OPC grape seed extract was, therefore, applied for the investigation using 3 groups of cultured primary cardiomyocytes: Group 1, blank control; Group 2, doxorubicin alone (10 microM) without OPC grape seed extract; Group 3, OPC grape seed extract (50 microg/ml) with doxorubicin (10 microM) for 24 hours. The intracellular ROS production was measured using 6-carboxy-2’,7’-dichlorodihydrofluorescein diacetate, and the cell death was assessed using propidium iodide. In Group 2, doxorubincin treatment increased the intracellular ROS production and induced significant cell death. Doxorubincin also caused the declined redox ratio of reduced glutathione (GSH)/oxidized glutathione (GSSG) and disrupted mitochondrial membrane potential as determined by 5,5’,6,6’-tetrachloro-1,1’,3,3’-tetraethlbenzimidazole-carbocyanide iodine (JC-1). Agarose gel electrophoresis indicated the fragmentation ladder of doxorubincin-induced nuclear DNA damage. OPC grape seed extract in Group 3 suppressed those alterations. Analysis using electron spin resonance spectroscopy shows that OPC group seed extract in Group 3 strongly scavenged hydroxyl radical, superoxide and DPPH radicals. Therefore, OPC grape seed extract as an antioxidant, when used in combination with doxorubicin can protect against doxorubicin-induced toxicity in cardiomyocytes. The combination of doxorubicin and OPC grape seed extract in treatment of MCF-7 human breast carcinoma cells did not decrease the proliferation-inhibitory effect of doxorubicin, as revealed by flow cytometric analysis. OPC grape seed extract may be used as a dietary antioxidant supplement in minimizing doxorubicin-induced cardiotoxicity, while antineoplastic activity of oxorubicin during chemotherapeutic treatment is not negatively affected. Back to Top
- Protective effects of grape seed proanthocyanidin extracts on cerebral cortex of streptozotocin-induced diabetic rats through modulating AGEs/RAGE/NF-kappaB pathway. J Nutr Sci Vitaminol (Tokyo). 2010; 56(2): 87-97.
OPC grape seed extract is potentially an effective dietary supplement for beneficial effects on diabetic encephalopathy, a severe disorder caused by oxidative stress in diabetic patients with long-term hyperglycemia. OPC grape seed extract as a natural polyphenolic antioxidant was tested in this study for possible reduction of the injuries in the cerebral cortex of diabetic rats. OPC grape seed extract may modulate advanced glycation end products (AGEs)/the receptor for AGEs (RAGE)/nuclear factor-kappa B p65 (NF-kappaB p65) pathway, which is crucial in oxidative stress. This study of OPC effect involved 3 tasks: 1) Body weight measuring and serum AGEs testing; 2) Isolation of cerebral cortexes for morphological observations and immunohistochemical stain of the pyramidal cell layers for the detection of RAGE, NF-kappaB p65, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1); 3) Determination of mRNA levels for RAGE and NF-kappaB p65, using quantitative reverse transcriptase coupled to polymerase chain reaction (RT-PCR) and western blot analysis for detection of protein expression. The long term hyperglycemia in diabetic rats was found to induce the degeneration of neurons and the up-regulation of serum AGEs. The hyperglycemia also resulted in the up-regulation of RAGE, NF-kappaB p65, VCAM-1 and ICAM-1 in the brain. The OPC grape seed extract treatment was found to improve the pathological changes of diabetic rats by regulating the AGEs/RAGE/NF-kappaB p65 pathway. This study of OPC grape seed extract in diabetic rats led to a fundamental understanding that the AGEs/RAGE/NF-kappaB pathway has a role in the pathogenesis of diabetic encephalopathy. This study supports the beneficial effects of the OPC grape seed extract as dietary supplement in the prevention and treatment of this disorder. Back to Top
- NFkappaB-dependent regulation of urokinase plasminogen activator by proanthocyanidin-rich grape seed extract: effect on invasion by prostate cancer cells. Blood Coagul Fibrinolysis. May 24, 2010.
Proanthocyanidin-rich grape seed extract (OPC) was investigated for the efficacy in regulating Urokinase plasminogen activator (uPA) expression and cell migration using highly metastatic androgen-independent PC-3 prostate cancer cells as a model. The OPC grape seed extract suppressed the uPA in a concentration-dependent fashion. This study further revealed the inhibition of DNA-binding activity of the transcription factor nuclear factor kappa B (NFkappaB) by the OPC grape seed extract. Consequently, NFkappaB-dependent uPA transcription was significantly reduced. The OPC grape seed extract inhibited PC-3 cell migration effectively as shown by invasion assays. Therefore, OPC grape seed extract may be used as a dietary supplement for prostate cancer patients and may be studied further as an antimetastatic agent by targeting uPA. Back to Top
- Dietary catechins and procyanidins modulate zinc homeostasis in human HepG2 cells. J Nutr Biochem. 2010 May 13.
Catechins and their oligomeric procyanidins (OPC) are health-promoting polyphenols found in a variety of edible vegetables and fruits. Grape seed extract OPC and related polyphenols are good chelators of redox-active metal ions such as iron and copper in the human body, and also act as antioxidants by scavenging reactive oxygen species. Catechin and OPC molecules have been demonstrated to be active as signaling molecules, modulating multiple cell signaling pathways and gene expression. They regulate the activities of a variety of enzymes, including that of antioxidant enzymes. In this study, catechins and OPC are evaluated for their possible interactions with the redo-inactive metal zinc and for their effect on cellular zinc homeostasis. In solution, OPC grape seed extract and the green tea extract (-)-epigallocatechin-3-gallate (EGCG) bind zinc ions more strongly than Zinquin, a zinc-specific chelator. In the cell culture, the lactate dehydrogenase test showed that OPC grape seed extract and the green tea extract (-)-epigallocatechin-3-gallate (EGCG) dose-dependently prevent zinc-induced toxicity in the human hepatocarcinoma cell line HepG2. The data from atomic flame absorption spectrometry indicated that OPC grape seed extract and (-)-epigallocatechin-3-gallate prevented intracellular accumulation of total zinc. In the meanwhile, they increased cytoplasmic labile zinc as detected by Zinquin fluorescence. OPC grape seed extract and (-)-epigallocatechin-3-gallate stimulated the expression of cellular zinc importers ZIP1 (SLC39A1) and ZIP4 (SLC39A4), while suppressing the expressions of zinc-binding metallothioneins and of plasma membrane zinc exporter ZnT1 (SLC30A1). OPC grape seed extract and (-)-epigallocatechin-3-gallate exhibited the same activity when HepG2 cells were supplemented with zinc or the proinflammatory cytokine interleukin-6. Overall, formation of extracellular zinc complexes and the increase of cytoplasmic labile zinc caused by supplementation of OPC grape seed extract and (-)-epigallocatechin-3-gallate may be associated with the polyphenolic activities in regulating cell signaling and metabolic pathways. Back to Top
- The molecular mechanism of protective effects of grape seed proanthocyanidin extract on reperfusion arrhythmias in rats in vivo. Biol Pharm Bull. 2010; 33(5): 759-67.
Reperfusion may lead to sudden death caused by reperfusion arrhythmias (RA) especially ventricular tachycardia (VT) and ventricular fibrillation (VF). OPC grape seed extract was demonstrated earlier in isolated rat hearts to reduce the incidence of reperfusion-induced VF and VT. This study was set to investigate possible mechanisms of this protection by OPC grape seed extract. Open chest anesthetized rats was used for coronary occlusion of 30 min and reperfusion of 120 min, affording a myocardial ischemia reperfusion (IR) model with clear ultrastructure of ischemic cardiomyocytes. Differentially expressed membrane proteins were identified using a technique of isobaric tag labeling for relative and absolute quantification (iTRAQ) proteomics, as verified by western blot analysis. It was found that OPC grape seed extract significantly reduced the incidence of VT and VF induced by reperfusion in vivo. OPC grape seed extract up-regulated expression of Na(+)/K(+)-ATPase alpha1 subunit (p<0.01), accompanied by 92 differentially expressed proteins that were identifiable. Reperfusion led to structural changes in the subunit distribution of Na(+)/K(+)-ATPase, and caused decrease in its alpha1 subunit, as not treated with OPC grapes seed extract. In contrast, the treatment with OPC grape seed extract in the sham group significantly increased Na(+)/K(+)-ATPase alpha1 subunit. This may be caused by the decreased free radical generation due to the antioxidant activity of OPC grape seed extract. The subunit distribution changes induced by OPC grape seed extract treatment may increase the activity of Na(+)/K(+)-ATPase. Therefore, OPC grape seed extract as dietary supplement may have the nutritional benefits against reperfusion arrhythmias, originated from its antioxidant activity. Back to Top
- Preventive effect of grape seed extract against high-fructose diet-induced insulin resistance and oxidative stress in rats. Food Chem Toxicol. Apr 20, 2010.
OPC grape seed extract is investigated for effect on insulin resistance and oxidative stress in rats fed a high-fructose diet. Supplementation of OPC grape seed extract in 1% of the total diet for 8 weeks lowered the fasting plasma glucose, insulin concentrations, and the homeostasis model assessment of basal insulin resistance of rats fed a high-fructose diet significantly, compared to those of a high-fructose diet group without feeding with OPC grape seed extract. After rats were fed a high-fructose diet containing 1% OPC grape seed extract, plasma glucose and insulin concentrations were found significantly lower after 15 min of glucose loading. Therefore, glucose intolerance of rats was improved by OPC grape seed extract supplementation. Further, the activities of 3 biological events, involving hepatic superoxide dismutase, catalase, and suppressed lipid peroxidation were largely increased in rats fed a high-fructose diet containing 1% OPC grape seed extract, when compared to rats fed a high-fructose diet without OPC grape seed extract. But the activity of hepatic glutathione peroxidase did not show a significant difference with or without OPC grape seed extract. It is concluded that OPC grape seed extract as an antioxidant is a good dietary supplement for patients of a high-fructose diet-induced insulin resistance and oxidative stress. Back to Top
- Effects of OPC grape pomace on the antioxidant defense system in diet-induced hypercholesterolemic rabbits. Nutr Res Pract. April 2010, 4(2):114-20.
OPC grape seed extract and grape skin extract prepared from grape pomace were investigated in rabbits fed on high cholesterol diet, for effect on the activity of antioxidant enzymes, degree of lipid peroxidation in serum and liver tissue. New Zealand white rabbits for the OPC activity were organized in 8 groups: Group 1, control; Group 2, cholesterol; Group 3, cholesterol + OPC grape seed extract; Group 4, cholesterol + OPC grape skin extract; Group 5, cholesterol + grape seed powder; Group 6, cholesterol + grape skin powder; Group 7, cholesterol + OPC grape seed extract and OPC grape skin extract; Group 8, cholesterol + grape seed and skin powder. After the feeding for 8 weeks, all the rabbits were sacrificed to remove the liver tissues. Then, GSH, GPx, GST, CAT and MDA in the liver were measured and compared for the OPC activity. The 3 antioxidant parameters, including total glutathione contents (GSH), glutathione peroxidase (GPX) and catalase (CAT) activity in liver were significantly higher with OPC grape seed extract supplementation in Group 3. The OPC grape seed extract in Group 3, grape skin powder in Group 6 and their combination in Group 7 also lowered the level of malondialdehyde (MDA) in the serum of rabbits with cholesterol diet, compared with the serum of Group 2 rabbits fed cholesterol without OPC grape seed extract. The results for Group 3 suggest that OPC grape seed extract functioned as antioxidants in vivo and relieved the oxidative stress induced by 1% cholesterol diet. The oxidized glutathione was effectively converted by OPC in Group 3 into reduced glutathione by the OPC grape seed extract feed. The grape peel powder slightly reduced the levels of the 3 liver antioxidant parameters of GSH, CAT and GPX activity. But it increased liver GST activity, producing combined effects of lipid peroxide and GSH, and resulting in the reduced formation of lipid peroxide in the serum. These results suggest that grape seed extract and grape peel powder activate the antioxidant enzyme system and prevent damage with hypercholesterolemia. Further, OPC grape seed extract in Groups 3 and 7 significantly reduced hydrogen peroxide created by oxidative stress. Back to Top
- Bioactive Dietary Polyphenols Decrease Heme Iron Absorption by Decreasing the Basolateral Iron Release in Human Intestinal Caco-2 Cells. J Nutr. April 7, 2010.
OPC and related polyphenolic compounds are good chelators of metal ions such as iron. The previous study showed that (-) -epigallocatechin-3-gallate (EGCG) and OPC grape seed extract have inhibitory effects on nonheme iron absorption. It was not clear whether the iron absorption from heme could also be affected by epigallocatechin-3-gallate EGCG and OPC grape seed extract. Heme (55)Fe in uptake buffer containing epigallocatechin-3-gallate EGCG or OPC grape seed extract in the apical compartment was used to incubate the fully differentiated intestinal Caco-2 cells grown on microporous membrane inserts for 7 hours. Both epigallocatechin-3-gallate EGCG and OPC grape seed extract reduced (P < 0.05) transepithelial transport of heme-derived iron. OPC grape seed extract increased apical heme iron uptake (P < 0.05), but suppressed the transfer of iron across the intestinal basolateral membrane and impaired the basolateral export. Epigallocatechin-3-gallate EGCG reduced the cellular assimilation of heme (55)Fe moderately, while the basolateral iron transfer was also very low. This means that epigallocatechin-3-gallate EGCG also inhibits the basolateral efflux of heme iron. Either EGCG or OPC grape seed extract did not change expression of heme oxygenase, ferroportin, and hephaestin protein. It is concluded that bioactive dietary OPC and epigallocatechin-3-gallate EGCG polyphenols inhibit heme iron absorption mainly by reducing basolateral iron exit. Back to Top
- Influence of gallate esterification on the activity of procyanidin B2 in androgen-dependent human prostate carcinoma LNCaP cells. April 2010, 27(4):619-27.
OPC grape seed extract contains many minor components including gallic esters. The 3 gallic esters derived from procyanidin B2 (B2), including B2-3,3'-di-O-gallate (B2-G(2)), two mono-gallate esters B2-3-O-gallate (B2-3G) and B2-3'-O-gallate (B2-3'G) and the parent compound B2, isolated from OPC grape seed extract were studied for their anti-cancer activity in androgen-dependent human prostate carcinoma LNCaP cells. The compounds were purified from OPC grape seed extract by several chromatographic steps, and were used to treat cells. The treated cells were evaluated for viability and apoptosis and examined by western blotting. The LNCaP cell viability was effectively decreased by Gallate esters B2-G(2), B2-3G and B2-3'G, but not by B2 and gallic acid. B2-G(2) was the only effective compound to suppress the cell growth. B2-G(2) and B2-3'G exerted comparable effects of apoptosis induction leading to suppressed cell viability. B2-3G was much less effective. B2-G(2) as a minor component in OPC grape seed extract exert significant anti-PCA efficacy. This contribution to the biological activity is mainly from gallate ester moiety at 3' position of procyanidin B2. Esterification at position 3 is not significant for the biological activity. The health benefits of OPC grape seed extract may be contributed partially from some of the gallate esters such as the B2-3,3'-di-O-gallate as the very minor component.
- The Effect of OPC Grape Seed Extracts on Serum Paraoxonase Activities in Streptozotocin-Induced Diabetic Rats. J Med Food 2010, 13 (3), 1–4.
Procyanidins or OPCs, are oligomeric forms of catechins that are abundant in red wine, grape skins, grape seeds, cocoa, and apples. OPC grape seed extract is studied in this article for effect on the activity of paraoxonase in streptozotocin-induced diabetic rats. The rats were organized in four groups: Group 1 (n = 8), control; Group 2 (n = 10), supplemented with OPC grape seed extract; Group 3 (n = 6), streptozotocin-induced diabetic; and Group 4 (n = 7), diabetic rats supplemented with OPC grape seed extract. Paraoxonase of the lowest activities was found in Group 3. Analysis of variance and Tukey’s HSD test were used for comparison between groups, and the relative index value P <.05 is considered significant. Effect of OPC grape seed extract was studied using rats in Group 3 as a control, Groups 1, 2, and 4 gave P values < .001, < .001, and = .005 respectively. The diabetic rats in Group 4, treated with OPC grape seed extract, showed increased paraoxonase activities compared to Group 3 (P = .005). This study demonstrated a correlation between paraoxonase activity and OPC grape seed extract supplementation. That is, OPC grape seed extract stimulated paraoxonase activities. This effect of OPC grape seed extract is more significant, relative to the diabetic rats in Group 3. Back to Top
- Antilisterial effects of a grape seed extract at low levels in aqueous media and its potential application as a produce wash. J Food Prot. Feb 2010, 73(2):266-73.
Grape seed extract proanthocyanidins (OPC) as a class of natural polyphenol antioxidants are reportedly able to serve as anti-inflammatory, anticarcinogenic, and antimicrobial agents. The ability of OPC grape seed extract to rapidly inactivate Listeria monocytogenes in vitro and the generally recognized safety of OPC grape seed extract make this OPC extract potentially very useful in control of food Listeria. OPC grape seed extract has been used earlier at 1% concentration in complex food matrices and in combination with other antimicrobials. The antilisterial effects of OPC grape seed extract alone at much lower concentrations of 0.00015 to 0.125% in aqueous solution was evaluated in this article, so that OPC grape seed extract could be possibly used as an antimicrobial wash for fresh produce surfaces. The abilities of OPC grape seed extract against L. monocytogenes Scott A and Listeria innocua ATCC 33090 were evaluated according to broth microdilution tests, and the MICs were determined to be as low as 50 and 78 mug/ml, respectively. OPC grape seed extract was evaluated in 0.85% saline against live cells of L. innocua via flow cytometry, and propidium iodide was used as a probe for membrane integrity. Rapid permeabilization and clumping of L. innocua was caused by treatment with OPC grape seed extract at sub-MICs and after only 2 min of exposure. OPC grape seed extract at a concentration of 0.125% reduced viable cell counts for L. monocytogenes by 2 log units in only 2 min on tomato surfaces. This research demonstrated the potential for OPC grape seed extract in control of Listeria spp. on low-complexity foods such as tomatoes. Back to Top
- Proteomics approach to study the mechanism of action of grape seed proanthocyanidin extracts on arterial remodeling in diabetic rats. Int J Mol Med. February 2010; 25(2): 237-48.
Streptozocin-induced diabetic rats were used in this study for the mechanism of functional protein changes during arterial remodeling caused by treatment with OPC grape seed extract. Rats were divided in 3 groups: Group 1, control (normal rats); Group 2, Diabetic rats; 3, diabetic rats treated with OPC grape seed extract. A daily dose of OPC grape seed extract in 250 mg/kg body weight was administrated to diabetic rats for 24 weeks. The aortic protein profiles for the 3 groups were then quantified and analyzed using 2-D difference gel electrophoresis and mass spectrometry. The OPC grape seed extract in Group 3 up-regulated or down-regulated the expression of 15 functional proteins, while in aorta of diabetic rats in Group 2 without the treatment with OPC grape seed extract, the expression of 23 proteins was affected. Therefore, OPC grape seed extract exerted biological activities to account for the difference of 7 proteins between the Group 2 and Group 3, which were not affected due to the OPC grape seed extract treatment. This investigation provided some new insights about the targets of grape seed extract OPCs in diabetic macrovascular complications. Back to Top
- Synergistic effects of combined phytochemicals and skin cancer prevention in SENCAR mice. Cancer Prevention Res. (Philadelphia, Pa.). Feb 2010; 3(2):170-8.
This is an investigation of the inhibitory effect of combined phytochemicals such as OPC grape seed extract and resveratrol on chemically induced murine skin tumorigenesis. The authors proposed a hypothesis that concurrent topical and dietary treatment with selected compounds such as resveratrol and OPCs in grape seed extract and red wine extract, would lead to more efficient prevention of skin cancer. The diet additives Ellagic acid and calcium D-glucarate were applied. Resveratrol was only used as topical agent. OPC grape seed extract was applied either topically or in the diet. The skin carcinogenesis model induced by 7,12-dimethylbenz[a]anthracene (DMBA) in SENCAR mice was used for 4-week inflammatory-hyperplasia assay. Remarkable decrease of epidermal thickness was observed with all the selected combination treatments involving resveratrol, as compared with the DMBA-treated group and also with groups treated with a single compound and DMBA. Each selected combination of resveratrol with other compounds including OPC grape seed extract, ellagic acid or calcium D-glucarate, exhibited a synergistic effect on hyperplasia and Ha-ras mutations. The combination treatments by resveratrol and OPC led to 3 consequences: 1, remarkably suppressed cell proliferation and Bcl2 expression; 2, decreased cell cycle regulator p21; and 3, reduced inflammation marker cyclooxygenase-2. The DMBA-induced mRNA expression of CYP1B1 was almost completely inhibited in every selected combination, and remarkable decreases of proto-oncogenes c-jun and c-fos, components of transcription factor activator protein, were observed. These results demonstrate additive or synergistic effects and their combined actions in the combination treatments, especially using resveratrol with ellagic acid, OPC grape seed extract. The combinations of resveratrol and other phytochemicals such as grape seed extract OPCs can act as potent inhibitors of skin tumorgenesis. Back to Top
- Dietary feeding of grape seed extract prevents intestinal tumorigenesis in APCmin/+ mice. Neoplasia. January 2010; 12(1): 95-102.
OPC grape seed extract was reportedly to have chemopreventive activities against intestinal/colon cancer development. In this research, the efficacy of OPC grape seed extract against intestinal tumorigenesis was investigated in APC(min/+) mice. The AIN-76A diet containing OPC grape seed extract (0.5%, wt/wt) was used to feed female APC(min/+) mice for 6 weeks. The diet containing OPC grape seed extract was found to decrease the total number of intestinal polyps by 40%, as compared with the group without OPC grape seed extract feeding. A total 42% decrease in the polyp formation in the small intestine was observed. Remarkable decreases were found in its middle 51% and in distal (49%) portions compared with the proximal one. OPC grape seed extract also caused decreases of polyps of 1 to 2 mm in size by 42% and bigger than 2 mm by 71%. OPC grape seed extract did not affect significantly polyps less than 1 mm. A decrease (80%-86%) in cell proliferation and an increase (4-8 fold) in apoptosis were observed in the small intestinal tissues with the treatment of OPC grape seed extract. OPC grape seed extract caused decreased levels of 3 functional proteins: COX-2 by 56%-64%, inducible nitric oxide synthase (iNOS) by 58%-60%, and beta-catenin by 43%-59%. OPC grape seed extract feeding increased Cip1/p21-positive cells by 1.9-2.6 fold. OPC grape seed extract also lowered cyclin D1 and c-Myc protein levels in small intestine. The OPC grape seed extract was found very effective against intestinal polyp formation and growth in APC(min/+) mice. OPC grape seed extract, therefore, has the potential usefulness and health benefits as a dietary supplement for the human intestinal/colorectal cancer patients.
- Decrease of adenosine deaminase activity and increase of the lipid peroxidation after acute methotrexate treatment in young rats: protective effects of grape seed extract. Cell Biochem Funct. Jan 2010; 28(1): 89-94.
An OPC grape seed extract was studied in rats for effect in alleviating the methotrexate (MTX)-induced side effects and the effect on adenosine deaminase activity (ADA).
MTX is an anti-folate agent for treating cancer and some inflammatory diseases with severe toxicity. Rats were divided in 3 groups. One of the groups were treated i.p. with a dose of 50 mg/kg body wt of OPC grape seed extract prior to the MTX treatment, which was then i.p. administered in 3 different times in a dose of 10 mg/kg body wt each time in 0, 4, and 16 hours. Other 2 groups (with and without MTX treatment as controls) were not treated with OPC grape seed extract. All rats in 3 groups were sacrificed 48 h after the last MTX administration, and the OPC effects were evaluated in 3 organs: hippocampus, kidney and liver. Without the OPC grape seed extract, the administration of MTX caused 3 consequent results: 1. The thiobarbituric acid reactive species (TBARS) levels were significantly increased in hippocampus, kidney and liver, resulting in a significant decreased in the ADA activity in the cerebral cortex, kidney and liver tissues. 2. The activity of ALT (alanine aminotransferase) and urea levels were increased significantly and serum uric acid levels were decreased. 3. Urinary uric acid levels were reduced as compared to those of the control group. The OPC grape seed extract significantly rescued these 3 MTX-induced parameter changes and drove them close to the normal levels. In conclusion, the OPC grape seed extract as a free radical scavenger could reduce MTX-induced hepatic and nephritic damages in rats, and should be useful as a dietary supplement for patients to relieve side effects of chemotherapy. Back to Top
- Downregulation of urokinase-type plasminogen activator and plasminogen activator inhibitor-1 by grape seed proanthocyanidin extract. Phytomedicine. January 2010; 17(1): 42-6.
A grape seed proanthocyanidin extract or OPC was investigated for activity in regulation of the 3 factors for normal wound healing: urokinase plasminogen activator (uPA), its receptor uPAR and inhibitor, type 1 plasminogen activator inhibitor (PAI-1). This study was based on earlier report that OPC grape seed extract has the nutritional benefit for wound healing. The OPC grapes seed extract in 3 different doses was used to treat fibroblast cells for 18 hours in culture, which were then processed for bioassays such as ELISA, RT-PCR, western blotting, fibrinolytic assay, cell surface plasmin activity assay and in vitro wound healing assay. The OPC grape seed extract suppressed uPA and PAI-1 expression. The decreases in uPA and PAI-1 activities were observed concentration-dependently by the OPC grape seed extract, as shown by the ELISA analysis. Consequently, fibrinolytic activity was decreased, concomitantly with decreased cell-surface plasmin activity. In vitro studies showed that the migration of cells towards the wounded region was significantly retarded by the OPC grape seed extract. Back to Top
- Effect of grape seed extract on blood pressure in subjects with the metabolic syndrome. Metabolism. Dec 2009; 58(12): 1743-6.
An OPC grape seed extract was studied in this article for possible effect on blood pressure. The patients were divided randomly in 3 groups: 1) placebo; 2) 150 mg OPC grape seed extract per day; and 3) 300 mg OPC grape seed extract per day. The 3 groups are treated for 4 weeks. Serum lipid levels and blood glucose levels were determined at both the beginning and the end of the 4 week period. The OPC grape seed extract lowered both the systolic and diastolic blood pressures as compared with placebo, as measured at both the beginning and the end of the 4 week period. The serum lipid levels and blood glucose values did not show significant differences between the 3 groups treated with OPC grape seed extract and placebo. This study shows that OPC grape seed extract may be used as a dietary supplement for people of hypertension.
- Grape seed extract suppresses lipopolysaccharide-induced matrix metalloproteinase (MMP) secretion by macrophages and inhibits human MMP-1 and -9 activities. J Periodontol. Nov 2009; 80(11): 1875-82.
AAn OPC grape seed extract was studied for the effect on 3 matrix metalloproteinases (MMP, MMP-1 and MMP-9) in the tissue destruction observed during periodontitis, a disease that affects tooth-supporting structures. The OPC grape seed extract affects MMP secretion by human monocyte-derived macrophages stimulated with Aggregatibacter actinomycetemcomitans lipopolysaccharide (LPS). The OPC grape seed extract also affect the activity of human recombinant MMP-1 and -9. The OPC grape seed extract of 3 different concentrations was used to treat macrophages, when were then stimulated with LPS. The effect of OPC grape seed extract was analyzed using ELISA for the 3 related parameters: 1, secretion of MMPs; 2, activation of nuclear factor-kappa B (NF-kappaB) p65; and 3, activator protein-1 (AP-1). It was found that the OPC grape seed extract inhibited secretion of MMP-1, -3, -7, -8, -9, and -13 by LPS-stimulated macrophages in a concentration-dependent fashion. The mechanism involved the down-regulation of NF-kappaB p65 and AP-1 activation by the OPC grape seed extract. The activities of MMP-1 and -9 were also inhibited. It was concluded that the OPC grape seed extract may be used as dietary supplement for people of periodontitis. Back to Top
- Anticancer and cancer chemopreventive potential of grape seed extract and other grape-based products. J Nutr. Sep 2009; 139(9): 1806S-12S.
This is a review article on OPC grape seed extract and grape-based products containing rich polypohenols including OPCs and anthocyanins as dietary supplements that have shown cancer chemopreventive potential and are also known to improve overall human health. The recent advancements in cancer chemopreventive and anticancer efficacy of OPC grape seed extract, OPC red wine extract and whole grape extract are summarized and discussed. It was concluded that many research groups have demonstrated OPC grape seed extract and related products are excellent sources of nutritional polyphenols of anticancer activities in cell culture or by animal models. The regular consumption of OPC grape seed extract might contribute to cancer chemoprevention at low expenses. Further clinical studies are still needed. Back to Top
- Cardioprotective roles of aged garlic extract, grape seed proanthocyanidin, and hazelnut on doxorubicin-induced cardiotoxicity. Can J Physiol Pharmacol. Aug 2009; 87(8): 633-40.
An OPC grape seed extract was among 3 different materials investigated for effects on
doxorubicin (DXR)-induced cardiotoxicity. DXR stimulates generation of oxygen free radicals that cause cell damage. The OPC grape seed extract as the strong antioxidants may suppress the free radical production and alleviate the cell damage. A total of 135 wistar albino male rats were divided equally to 9 groups. The 3 antioxidants including aged garlic extract, OPC grape seed extract proanthocyanidin and hazelnut, were supplied to 3 different groups of the rats in their standard rat diet. DXR was used to treat the rats i.p. in 2 different doses: 3.75 mg/kg each week for 4 weeks; 1.875 mg/kg each week for 4 weeks. The control group was treated i.p. with 0.9% saline. Aged garlic extract, OPC grape seed extract proanthocyanidin and hazelnut, were fed the groups starting 1 week before the DXR treatment and ending 1 week after the treatment, lasting for a total of 6 weeks. Malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and xanthine oxidase (XO) levels were quantified from heart tissue samples a week after the last DXR injection, and serum samples were taken for creatine kinase (CK). The MDA level remains unchanged for all groups - the control, DXR-treated groups, or the groups treated with garlic extract, OPC grape seed extract and hazelnut. DXR caused decreases in SOD enzyme levels. The OPC grape seed extract rescued the decrease at low doses of DXR. CAT enzyme levels are decreased by DXR treatment, but increased by OPC grape seed extract and hazelnut consumption at low cumulative doses. OPC grape seed extract prevented the decrease of XO enzyme levels, but garlic extract and hazelnut did not. OPC grape seed extract prevented the increase of CK levels caused by DXR administration. Electron microscopy analysis revealed the significant protective effects of garlic extract and OPC grape seed extract in the prevention of DXR-induced cardiac injury. The detailed mechanisms at the enzyme levels remain unclear. The 2 antioxidants of garlic extract and OPC grape seed extract could be very beneficial for the heart health in the long-term consumption as a dietary supplement. Back to Top
- Antioxidant effects of OPC grape seed extract in a rat model of diabetes mellitus. Diab Vasc Dis Res. July 2009, 6(3):200-4.
OPC grape seed extract is studied for the anti-hyperglycaemic and antioxidant effect in normal and streptozotocin-induced diabetic Wistar rats. Adult male Wistar rats of 3 sets were used: Set 1: non-diabetic control; Set 2: diabetic control; Set 3: diabetic rats orally administered with OPC grape seed extract, via an intragastric tube (0.6 ml/rat), at a dose of 100 mg/kg for 20 days after diabetes mellitus was introduced. The measured results showed that OPC grape seed extract at 100 mg/kg/day, reduced the levels of lipid peroxides and carbonylated proteins. The OPC grape seed extract also improved the antioxidant activity in plasma and hepatic tissue in rats treated with OPC grape seed extract as compared with the diabetic control rats without OPC grape seed extract. The conclusion is that OPC grape seed extract enhanced the antioxidant defense against reactive oxygen species produced under hyperglycaemic conditions. The OPC grape seed extract can protect the liver cells from damages caused by oxidative stress. Back to Top
- Dietary procyanidins (OPC) enhance transcriptional activity of bile acid-activated FXR in vitro and reduce triglyceridemia in vivo in a FXR-dependent manner. Mol Nutr Food Res. Jul 2009; 53(7): 805-14.
An OPC grape seed extract was earlier demonstrated the activity to reduce postprandial triglyceridemia in normolipidemic animals. The biochemical mechanism involves signal transduction of the orphan nuclear receptor small heterodimer partner (SHP) - a target of the bile acid receptor farnesoid X receptor (FXR). The effect of OPC grape seed extract on hypotriglyceridemic level and the biochemical mechanism were investigated in the current study. The goal is to understand whether FXR mediates the effect of procyanidins - OPC. In FXR-driven luciferase expression assays, the OPC grape seed extract up-regulated FXR activity concentration-dependently in the presence of chenodeoxycholic acid. Triglyceridemia was reduced by feeding of OPC grape seed extract in wild type mice but not in FXR-null mice. Therefore, FXR is the essential mediator for the activity of OPC in the reduction of the hypotriglyceridemic levels in vivo. The expression of the transcription factor -steroid response element binding protein 1 (SREBP1) and several SREBP1 target genes involved in lipogenesis were suppressed by the OPC grape seed extract in the liver by the OPC grape seed extract. The expression of ApoA5 was stimulated. The OPC grape seed extract lowers triglyceridemia via the same biochemical mechanism as bile acids: enhancement of FXR activity, leading to transient increase of SHP level and a subsequent decrease of SREBP1 level. Therefore, the OPC grape seed extract as a dietary supplement has the nutritional benefits for 3 types of patients of hypertriglyceridemia, type 2 diabetes and metabolic syndrome. And the new insight of biochemical mechanism is established involving FXR as the signal mediator. Back to Top
- Protective effect of grape seed proanthocyanidins extracts on reperfusion arrhythmia in rabbits. J Nutr Sci Vitaminol (Tokyo). Jun 2009; 55(3): 223-30.
A grape seed proanthocyanidins extract (OPC) was studied in this research for possible effects on reperfusion arrhythmia (RA), - a complication and also an important cause of sudden cardiac death. This OPC grape seed extract was administered for 3 weeks into rabbits of the cardiac ischemic reperfusion injury. The OPC grape seed extract was applied for 3 groups of the rabbits in 3 different doses (250, 100, and 0 mg/kg body weight per day, respectively). The OPC grape seed extract significantly decreased the incidence of Ventricular fibrillation and the infarction size among the 3 groups of rabbits. Collapse and displacement of the intercalated disks and the formation of cisterns were observed in the control group without the treatment of the OPC grape seed extract. The OPC grape seed extract treatment improved intercalated disks, and much less collapse and displacement were observed. The OPC grape seed extract improved the expression of connexin 43, as detected by immunohistochemistry. The high dose of OPC grape seed extract among the 3 groups of rabbits gave more significant improvement. The OPC grape seed extract inhibited the degradation of connexin 43, enhanced gap junctional conductance, and exhibited a protective effect on myocardial ischemic reperfusion arrhythmias.
† These statements have not been evaluated by the US Food & Drug Administration.
FrenchGlory ® isotonic OPC 3 antioxidants are nutritional supplements for a variety of nutrition-deficient health problems due to imbalanced diet. They are not intended to diagnose, treat, care or prevent other general diseases.