Grape seed is used for treating and preventing vascular or circulatory disorders including venous insufficiency, varicose veins, atherosclerosis, hypertension, diabetic neuropathy or retinopathy, peripheral vascular disease, edema associated with injury or surgery and myocardial or cerebral infarction. It is also used for improving wound healing, preventing dental caries, cancer prevention, macular degeneration, poor night vision, liver cirrhosis, allergic rhinitis and prevention of collagen breakdown associated with collagen diseases and aging. Grape seed extract contains oligomeric proanthocyanidins (OPCs) or procyanidins which are responsible fore these (antioxidant) actions.
Preliminary evidence suggests grape seed proanthocyanidins may provide greater protection against reactive oxygen species, free radical-induced lipid peroxidation and DNA damage than the combination of vitamin E, vitamin C and beta-carotene, or a combination of vitamin E and vitamin C. Grape seed proanthocyanidins seem to inhibit the cytochrome P450 2E1 (CYP2E1) enzyme, which might protect normal cells against drug and chemical-induced toxicity. There is preliminary evidence that grape seed proanthocyanidins might protect against tobacco-induced and chemotherapy drug-induced damage to normal cells. Grape seed proanthocyanidins seem to decrease the proliferation of gastric adenocarcinoma, breast cancer, lung cancer, prostate cancer cells by inhibiting cell growth and increasing cell death. OPCs are also thought to inhibit the proteolytic enzymes collagenase, elastase, hyaluronidase and beta glucuronidase, which are involved in the breakdown of structural components of the vasculature and skin. Grape seeds also contain catechin, which preclinical research suggests might inhibit allergen-induced histamine release from mast cells.
back to top
Published Clinical Studies
The effect of grape-seed extract on 24 h energy intake in humans.1
Vogels N, Nijs IM, Westerterp-Plantenga MS.
Maastricht University, Human Biology, Maastricht, The Netherlands. N.Vogels@HB.Unimaas.NL
OBJECTIVE: Since grape-seed extract has been shown to stimulate lipolysis in vitro and reduce food intake in rats, we assessed the efficacy of grape-seed extract with respect to energy intake (EI) and satiety. DESIGN: In a randomized, placebo-controlled, double-blind, cross-over study, 51 subjects (age 18-65 y, body mass index 22-30 kg/m2) ate an ad libitum lunch and dinner twice in the University Restaurant for 3 days. Standard breakfasts and snacks were provided. Supplements were taken 30-60 min prior to each meal. RESULTS: In the total study population, no difference in 24 h EI was found between the grape-seed extract and placebo. However, in the subgroup of subjects (n=23) with an energy requirement > or =the median of 7.5 MJ/day, EI was reduced by 4% (DeltaEI 352.1 kJ/24 h, P=0.05) after grape-seed extract compared to placebo treatment. Meanwhile, there were no significant differences in macronutrient composition, attitude towards eating, satiety, mood or tolerance. CONCLUSIONS: Grape seed reduced 24 h EI, with on average 4% in subjects who had an energy requirement > or =7.5 MJ/day, without further effects on satiety, mood or tolerance. These findings suggest that grape seed could be effective in reducing 24 h EI in normal to overweight dietary unrestrained subjects, and could, therefore, play a significant role in body-weight management.
PMID: 15042136 [PubMed - in process]
Phenolic compounds and antioxidant activity from red grape marc extracts.2
Negro C, Tommasi L, Miceli A.
Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Universita Degli Studi di Lecce, Via per Monteroni, 73100 Lecce, Italy.
The aims of this work were to determine the amounts of the different classes of phenolic compounds in an ethanolic extract from red grape marc and its components, peels and seeds, and to evaluate their antioxidant activities by the beta-carotene bleaching test for their utilization as natural antioxidants. The results showed that red grape marc was rich in polyphenol compounds with a clear antioxidant activity. The extracts, in fact, at very low concentration (20 ppm) in total phenols showed an antioxidant activity (AA) higher than 43% on average, while at higher concentration (80-160 ppm) all the fractions had an AA comparable to that of butlylated-hydroxytoluene. Grape seeds seemed to give the highest contribution to such AA, as they contained high quantities of proanthocyanidines, a type of flavonoid known for its high antioxidant properties.
PMID: 12733573 [PubMed - indexed for MEDLINE]
Study of anti-atherosclerosic effect of grape seed extract and its mechanism3
Yu H, Wang SE, Zhao C, Xu G.
School of Public Health, Shandong University, Jinan 250012, China.
In order to observe the anti-atherosclerosic effect of the grape seed extract and its mechanism, the 50C57/6J mice are divided randomly into 5 group (normal control group, hyperlipidemia model group, low and high grape seed extract groups(0.2 mg/gBW, 0.6 mg/gBW), and drug control group(0.2 mg/gBW). After twenty-one weeks, plasma oxidized low density lipoprotein (OX-LDL), serum nitric oxide (NO) and intercellular adhesion molecule-1 (ICAM-1) are measured and the form of aortic valves are observed pathologically. The results show that the levels of plasma OX-LDL, and ICAM-1 are significantly lower in grape seed extract group than those in model group while the levels of NO are higher in grape seed extract group than that in model group (P < 0.01). The thickness of aortic valves consisting of foam cell and endothelium hyperplasia in grape seed extract group is lighter than that of model group. The results indicate that the grape seed extract has inhibitary effect on atherosclerosis in C57BL/6J mice, and the possible mechanism may be related to inhibition of the increase of OX-LDL, and ICAM-1, reduction of the damage of vascular endothelium and protection of the function of vascular endothelium.
PMID: 12600036 [PubMed - indexed for MEDLINE]
Mechanistic pathways of antioxidant cytoprotection by a novel IH636 grape seed proanthocyanidin extract.
Bagchi D, Ray SD, Bagchi M, Preuss HG, Stohs SJ.
Creighton University School of Pharmacy & Allied Health Professions, Omaha, NE 68178, USA. email@example.com
To understand the bioavailability and mechanistic pathways of cytoprotection by IH636 grape seed proanthocyanidin extract (GSPE, commercially known as ActiVin) a series of in vitro and in vivo studies were conducted. Comparative protective abilities of GSPE, and vitamins C and E, singly and in combination, were assessed against smokeless tobacco extract (STE)-induced oxidative stress, DNA fragmentation and apoptotic cell death in a primary culture of normal human oral keratinocytes. GSPE protected against STE-induced oxidative stress, DNA damage and apoptotic cell death, and provided better protection as compared to vitamins C and E, singly and in combination. The bioavailability and protective ability of GSPE were examined against acetaminophen (AP)-induced hepato- and nephrotoxicity, amiodarone (AM)-induced lung toxicity, doxorubicin (DX)-induced cardiotoxicity and dimethylnitrosamine (DM)-induced spleenotoxicity in mice. GSPE-fed animals were compared with GSPE-untreated mice to evaluate the protective ability of GSPE against these structurally diverse drugs/chemicals. Serum chemistry changes, histopathology and DNA damage were evaluated. Results indicate that GSPE preexposure prior to the drugs/chemicals such as AP, AM, DX or DM treatment, provided near complete protection in terms of serum chemistry changes and inhibition of both forms of cell death, e.g., apoptosis and necrosis. DNA damage in various tissues triggered by these agents was significantly reduced in GSPE-fed animals. Histopathological examination of multiple target organs provided similar data. The results suggest that GSPE exposure is bioavailable and provides significant multiorgan protection against structurally diverse drug- and chemical-induced toxic assaults. Further, these studies exhibited a series of mechanistic information including free radical scavenging ability, anti-endonucleolytic activity, cytochrome P450 2E1 inhibitory activity, anti-necrotic, anti-apoptotic and anti-carcinogenic activities, modulatory effects on antioxidative and apoptotic regulatory genes such as Bcl2, c-myc and p53, which may be responsible for the novel chemoprotective properties exhibited by GSPE.
Cellular protection with proanthocyanidins derived from grape seeds.5
Bagchi D, Bagchi M, Stohs S, Ray SD, Sen CK, Preuss HG.
Department of Pharmacy Services, Creighton University School of Pharmacy & Allied Health Professions, Omaha, Nebraska 68178, USA. firstname.lastname@example.org
Grape seed proanthocyanidins have been reported to possess a broad spectrum of pharmacological and medicinal properties against oxidative stress. We have demonstrated that IH636 proanthocyanidin extract (GSPE) provides excellent protection against free radicals in both in vitro and in vivo models. GSPE had significantly better free radical scavenging ability than vitamins C, E and beta-carotene and demonstrated significant cytotoxicity towards human breast, lung and gastric adenocarcinoma cells, while enhancing the growth and viability of normal cells. GSPE protected against tobacco-induced apoptotic cell death in human oral keratinocytes and provided protection against cancer chemotherapeutic drug-induced cytotoxicity in human liver cells by modulating cell cycle/apoptosis regulatory genes such as bcl2, p53 and c-myc. Recently, the bioavailability and mechanistic pathways of cytoprotection by GSPE were examined on acetaminophen-induced hepatotoxicity and nephrotoxicity, amiodarone-induced pulmonary toxicity, doxorubicin-induced cardiotoxicity, DMN-induced immunotoxicity and MOCAP-induced neurotoxicity in mice. Serum chemistry changes, integrity of genomic DNA and histopathology were assessed. GSPE pre-exposure provided near complete protection in terms of serum chemistry changes and DNA damage, as well as abolished apoptotic and necrotic cell death in all tissues. Histopathological examination reconfirmed these findings. GSPE demonstrated concentration-/dose-dependent inhibitory effects on the drug metabolizing enzyme cytochrome P450 2E1, and this may be a major pathway for the anti-toxic potential exerted by GSPE. Furthermore, GSPE treatment significantly decreased TNFalpha-induced adherence of T-cells to HUVEC by inhibiting VCAM-1 expression. These results demonstrate that GSPE is highly bioavailable and may serve as a potential therapeutic tool in protecting multiple target organs from structurally diverse drug- and chemical-induced toxicity.
PMID: 12074978 [PubMed - indexed for MEDLINE]
Oxygen free radical scavenging abilities of vitamins C and E, and a grape seed proanthocyanidin extract in vitro.
Bagchi D, Garg A, Krohn RL, Bagchi M, Tran MX, Stohs SJ.
School of Pharmacy, Creighton University, Omaha, NE 68178, USA.
Proanthocyanidins, a group of polyphenolic bioflavonoids, have been reported to exhibit a wide range of biological, pharmacological and chemoprotective properties against oxygen free radicals. We have assessed the concentration-dependent oxygen free radical scavenging abilities of a grape seed proanthocyanidin extract (GSPE), vitamin C and vitamin E succinate (VES) as well as superoxide dismutase, catalase and mannitol against biochemically generated superoxide anion and hydroxyl radical using a chemiluminescence assay and cytochrome c reduction. A concentration-dependent inhibition was demonstrated by GSPE. At a 100 mg/l concentration, GSPE exhibited 78-81% inhibition of superoxide anion and hydroxyl radical. Under similar conditions, vitamin C inhibited these two oxygen free radicals by approximately 12-19%, while VES inhibited the two radicals by 36-44%. The combination of superoxide dismutase and catalase inhibited superoxide anion by approximately 83%, while mannitol resulted in an 87% inhibition of hydroxyl radical. The results demonstrate that GSPE is a more potent scavenger of oxygen free radicals as compared to vitamin C and VES.
PMID: 9090754 [PubMed - indexed for MEDLINE]
back to top
Covington TR, ed. The Handbook of Non-Prescription Drugs. Washington, DC: APhA, 1996.
Bombardelli E, Morazzoni P. Vitis vinifera L. Fitoterapia 1995; LXVI:291-317.
Anon. OPCs (Oligomeric Proanthocyanidins). The Natural Pharmacist 2000. http://www.tnp.com/substance.asp?ID=181. (Accessed 3 June 2000).
Peirce A. The American Pharmaceutical Association Practical Guide to Natural Medicines. New York, NY: William Morrow and Co., 1999.
Bernstein DI, Bernstein CK, Deng C, et al. Evaluation of the clinical efficacy and safety of grapeseed extract in the treatment of fall seasonal allergic rhinitis: a pilot study. Ann Allergy Asthma Immunol 2002;88:272-8.
Nuttall SL, Kendall MJ, Bombardelli E, Morazzoni P. An evaluation of the antioxidant activity of a standardized grape seed extract, Leucoselect. J Clin Pharm Ther 1998;23:385-89.
Bagchi D, Bagchi M, Stohs SJ, et al. Cellular protection with proanthocyanidins derived from grape seeds. Ann N Y Acad Sci 2002;957:260-70.
Pataki T, Bak I, Kovacs P, et al. Grape seed proanthocyanidins improved cardiac recovery during reperfusion after ischemia in isolated rat hearts. Am J Clin Nutr 2002;75:894-9.
Agarwal C, Sharma Y, Agarwal R. Anticarcinogenic effect of a polyphenolic fraction isolated from grape seeds in human prostate carcinoma DU145 cells: modulation of mitogenic signaling and cell-cycle regulators and induction of G1 arrest and apoptosis. Mol Carcinog 2000;28:129-38.