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14. Photomed Laser Surg. 2011 Nov 21. [Epub ahead of print]  Topical Grape Seed Proanthocyandin Extract Reduces Sunburn Cells and Mutant p53 Positive Epidermal Cell Formation, and Prevents Depletion of Langerhans Cells in  an Acute Sunburn Model.  Yuan XY, Liu W, Hao JC, Gu WJ, Zhao YS.  1 Department of Dermatology, the General Hospital of the Air Force , Beijing, China . 

 Abstract Objective: The purpose of this study was to investigate whether grape seed proanthocyanidin extract (GSPE) can provide photoprotection against ultraviolet (UV) irradiation. Background data: Study has shown that GSPE is a natural oxidant, and is used in many fields such as ischemia-reperfusion injury,  chronic pancreatitis, and even cancer. However, the effect of GSPE on UV irradiation is as yet unknown. Methods: Cutaneous areas on the backs of normal volunteers were untreated or treated with GSPE solutions or vehicles 30?�min before exposure to two minimal erythema doses (MED) of solar simulated radiation. Cutaneous areas at different sites were examined histologically for the number of sunburn cells, or immunohistochemically for Langerhans cells and mutant p53 epidermal cells. Results: On histological and immunohistochemical examination, skin treated with GSPE before UV radiation showed fewer sunburn cells and mutant  p53-positive epidermal cells and more Langerhans cells compared with skin treated with 2-MED UV radiation only (p<0.001, p<0.001, and p<0.01, respectively). Conclusions: GSPE may be a possible preventive agent for photoprotection.  PMID: 22103910  [PubMed - as supplied by publisher] 

13. Mini Rev Med Chem. 2011 Oct 28. [Epub ahead of print]  Polyphenols: Skin Photoprotection and Inhibition of Photocarcinogenesis.  Afaq F, Katiyar SK.  Department of Dermatology,University of Alabama at Birmingham, 1670 University Boulevard, VolkerHall 557, Birmingham, AL 35294, USA. 

 Polyphenols are a large family of naturally occurring plant products and are widely distributed in plant foods, such as, fruits, vegetables, nuts, flowers, bark and seeds, etc. These polyphenols contribute to the beneficial health effects of dietary products. Clinical and epidemiological studies suggest that exposure of the skin to environmental factors/pollutants, such as solar ultraviolet (UV) radiation induce harmful effects and leads to various skin diseases including the risk of melanoma and non-melanoma skin cancers. The incidence of non-melanoma skin cancer, comprising of squamous cell carcinoma and  basal cell carcinoma, is a significant public health concern world-wide. Exposure of the skin to solar UV radiation results in inflammation, oxidative stress, DNA  damage, dysregulation of cellular signaling pathways and immunosuppression thereby resulting in skin cancer. The regular intake of natural plant products, especially polyphenols, which are widely present in fruits, vegetables, dry legumes and beverages have gained considerable attention as protective agents against the adverse effects of UV radiation. In this article, we first discussed  the impact of polyphenols on human health based on their structure-activity relationship and bioavailability. We then discussed in detail the photoprotective effects of some selected polyphenols on UV-induced skin inflammation, proliferation, immunosuppression, DNA damage and dysregulation of important cellular signaling pathways and their implications in skin cancer management. The selected polyphenols include: green tea polyphenols, pomegranate fruit extract, grape seed proanthocyanidins, resveratrol, silymarin, genistein and delphinidin.  The new information on the mechanisms of action of these polyphenols supports their potential use in skin photoprotection and prevention of photocarcinogenesis in humans.  PMID: 22070679  [PubMed - as supplied by publisher] 

12. Int Wound J. 2011 Oct;8(5):514-20. doi: 10.1111/j.1742-481X.2011.00833.x. Epub 2011 Aug 4.  Topical grape (Vitis vinifera) seed extract promotes repair of full thickness wound in rabbit.  Hemmati AA, Aghel N, Rashidi I, Gholampur-Aghdami A.  Department of Pharmacology and Toxicology, School of Pharmacy and Medicinal Research Center, Ahwaz, Iran. 

 In recent years, oxidative stress and free radicals have been implicated in impaired wound healing. Grape (Vitis vinifera) seed extract (GSE) possesses anti-inflammatory and antioxidant properties. The present study was undertaken to assess the potential activity of grape seed hydroalcoholic extract in wound healing in rabbits. Rabbits of either sex were subjected to a 20 ? 20 mm square excision made over the skin of the back. The animals were randomly divided into seven experimental groups, as negative and positive control, eucerin and treatments. Negative control group did not receive any treatment. Positive control and eucerin groups received phenytoin cream (1%) and topical eucerin, respectively, twice a day from the beginning of experiments to complete wound closure. Treatment groups were treated topically by cream of GSE (2, 5, 10 and 70% w/w) in eucerin base, twice daily. For evaluation of the percentage of wound  healing, area of the wound was measured daily. Histological studies were performed on the 7th and 15th days of treatments. After complete healing, hydroxyproline content and tensile strength measurement of tissue samples were done. Results showed that there were statistically significant differences between GSE treatments groups and eucerin animals (P < 0·05) in most of the days. Rabbits treated with 2% GSE had best results (completed healing in 13 days, higher hydroxyproline content and higher tissue resistance). We concluded that the extract of 2% GSE administered topically has a good potential to promote wound healing in wound model of rabbits.  © 2011 The Authors. © 2011 Blackwell Publishing Ltd and Inc.  PMID: 21816000  [PubMed - in process]  

11. J Med Food. 2011 Jul-Aug;14(7-8):761-6. Epub 2011 Apr 6.  Photoprotective effects of two natural products on ultraviolet B-induced oxidative stress and apoptosis in SKH-1 mouse skin.  Filip A, Daicoviciu D, Clichici S, Mocan T, Muresan A, Postescu ID.  Department of Physiology, "Iuliu Hatieganu" University of Medicine and Pharmacy,  Cluj-Napoca, Romania. 

 Solar ultraviolet radiation (UV) is the major cause of nonmelanoma skin cancer in humans. Photochemoprevention with natural products represents a simple but very effective strategy for the management of cutaneous neoplasia. We studied the photoprotective activity of Calluna vulgaris and red grape seed (Vitis vinifera L, Burgund Mare variety [BM]) extracts in vivo in an SKH-1 hairless mice skin model. Fifty 8-week-old female SKH-1 hairless mice were randomly divided into 5 groups (n????0 each): controls, UVB-irradiated, C. vulgaris plus UVB-irradiated,  BM plus UVB-irradiated, and epigallocatechin gallate (EGCG) plus UVB-irradiated.  A dose of 4 mg/mouse per cm² of skin area for both extracts was topically applied to the mice 30 minutes before a single-dose (240 mJ/cm²) UVB exposure. EGCG dissolved in phosphate-buffered saline (pH 6.6; 0.067 M) was administered at 2 mg/mouse per cm². Glutathione peroxidase and catalase activities, reduced glutathione (GSH), malondialdehyde, nitric oxide, and caspase 3 activity were determined in skin homogenates 24 hours after irradiation. A single dose of UVB increased GSH levels and glutathione peroxidase activity in the exposed skin. C.  vulgaris and BM pretreatment significantly decreased GSH formation and glutathione peroxidase activity (P??
10. Nutr Cancer. 2011;63(1):28-38.  Inhibition of murine skin carcinogenesis by freeze-dried grape powder and other grape-derived major antioxidants.  Hanausek M, Spears E, Walaszek Z, Kowalczyk MC, Kowalczyk P, Wendel C, Slaga TJ.  The University of Texas Health Science Center at San Antonio, Department of Pharmacology, San Antonio, Texas 78229, USA. 

 Overexposure of the skin to carcinogenic insults causes a variety of adverse effects, among them the development of skin carcinomas. Since there is a need to  develop efficient chemopreventive agents based on nutrition, our goal was to determine antioxidant and anti-carcinogenic properties of grapes by evaluating grape powder developed by the California Table Grape Commission. In order to elucidate the mechanism(s) of action of grape powder, three of the major antioxidant components found in grapes-resveratrol, catechin, quercetin, and grape seed extract, containing a proanthocyanidin B-2-gallate-were evaluated for  their abilities to inhibit oxidative stress and to protect the immune system. Tested antioxidants given topically and/or systemically strongly inhibited 7,12-dimethylbenz[a]anthracene (DMBA)-induced epidermal hyperplasia, proliferation, and inflammation. The hydroxylation of 2'-deoxyguanosine was markedly inhibited by topical and dietary administration of test variables, i.e., by approximately 40-70%. Simultaneous dietary and topical treatment with antioxidants reduced these biomarkers, showing strong additive and in some combinations synergistic effects. DMBA-mediated Ha-ras mutations in codon 61 were reduced by up to 50% with topical applications, but much higher inhibition was observed in mice treated with different combinations. The results of the present  study clearly show impressive effects of combined topical and dietary treatments  with above grape-derived antioxidants.  PMID: 21108125  [PubMed - indexed for MEDLINE] 

9. Arch Dermatol Res. 2010 Mar;302(2):71-83. Epub 2009 Nov 7.  Skin photoprotection by natural polyphenols: anti-inflammatory, antioxidant and DNA repair mechanisms.  Nichols JA, Katiyar SK.  Department of Dermatology, University of Alabama at Birmingham, 1670 University Boulevard, Volker Hall 557, PO Box 202, Birmingham, AL 35294, USA. 

 Epidemiological, clinical and laboratory studies have implicated solar ultraviolet (UV) radiation in various skin diseases including, premature aging of the skin and melanoma and non-melanoma skin cancers. Chronic UV radiation exposure-induced skin diseases or skin disorders are caused by the excessive induction of inflammation, oxidative stress and DNA damage, etc. The use of chemopreventive agents, such as plant polyphenols, to inhibit these events in UV-exposed skin is gaining attention. Chemoprevention refers to the use of agents that can inhibit, reverse or retard the process of these harmful events in the UV-exposed skin. A wide variety of polyphenols or phytochemicals, most of which are dietary supplements, have been reported to possess substantial skin photoprotective effects. This review article summarizes the photoprotective effects of some selected polyphenols, such as green tea polyphenols, grape seed proanthocyanidins, resveratrol, silymarin and genistein, on UV-induced skin inflammation, oxidative stress and DNA damage, etc., with a focus on mechanisms underlying the photoprotective effects of these polyphenols. The laboratory studies conducted in animal models suggest that these polyphenols have the ability to protect the skin from the adverse effects of UV radiation, including the risk of skin cancers. It is suggested that polyphenols may favorably supplement sunscreens protection, and may be useful for skin diseases associated  with solar UV radiation-induced inflammation, oxidative stress and DNA damage.  PMCID: PMC2813915 PMID: 19898857  [PubMed - indexed for MEDLINE]  

8. J Cardiovasc Pharmacol. 2005 Oct;46(4):445-51.  Grape seed and skin extracts inhibit platelet function and release of reactive oxygen intermediates.  Vitseva O, Varghese S, Chakrabarti S, Folts JD, Freedman JE.  Whitaker Cardiovascular Institute and Evans Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA. 

 Red wine and purple grape juice contain polymeric flavonoids with antioxidant properties believed to be protective against cardiovascular events but the alcohol and sugar content of these beverages has curtailed their medicinal use. Acute cardiac events are also associated with enhanced inflammation and thrombosis. In this study, the extracts from grape skins or seeds were examined for their anti-inflammatory properties and effect on platelet release of reactive oxygen intermediates. Incubation of platelets with seed or skin extract led to a  decrease in platelet aggregation from 68.8+/-19.8% to 45+/-3.6% for seeds and to  27+/-7.2% for skin, respectively (P<0.05). Platelet incubation with grape skin or seed extracts led to a marked decrease in superoxide release from 73+/-6.2 to 2+/-3.4 for grape seeds and to 0.33+/-0.57 for grape skin (chemilum. units; P<0.05) as well as a significant increase in radical-scavenging activity, decrease in reactive oxygen species release by confocal microscopy, and enhanced  platelet NO was measured using an NO-sensitive microelectrode. These effects were dose dependent for both grape extracts. Coincubation with seeds and skins led to  additive inhibition of platelet aggregation, enhanced NO release, and prevented superoxide production. Incubation with seed or skin extracts led to an immediate  attenuation of release of the inflammatory mediator, soluble CD40 ligand. Thus, the extracts from purple grape skins and seeds inhibit platelet function and platelet-dependent inflammatory responses at pharmacologically relevant concentrations. These findings suggest potentially beneficial platelet-dependent  antithrombotic and anti-inflammatory properties of purple grape-derived flavonoids.  PMID: 16160595  [PubMed - indexed for MEDLINE] 

7. J Med Food. 2003 Winter;6(4):291-9.  Polyphenolics in grape seeds-biochemistry and functionality.  Shi J, Yu J, Pohorly JE, Kakuda Y.  Food Research Center, Agriculture and Agri-Food Canada, Guelph, Canada. 

 Grape seeds are waste products of the winery and grape juice industry. These seeds contain lipid, protein, carbohydrates, and 5-8% polyphenols depending on the variety. Polyphenols in grape seeds are mainly flavonoids, including gallic acid, the monomeric flavan-3-ols catechin, epicatechin, gallocatechin, epigallocatechin, and epicatechin 3-O-gallate, and procyanidin dimers, trimers, and more highly polymerized procyanidins. Grape seed extract is known as a powerful antioxidant that protects the body from premature aging, disease, and decay. Grape seeds contains mainly phenols such as proanthocyanidins (oligomeric  proanthocyanidins). Scientific studies have shown that the antioxidant power of proanthocyanidins is 20 times greater than vitamin E and 50 times greater than vitamin C. Extensive research suggests that grape seed extract is beneficial in many areas of health because of its antioxidant effect to bond with collagen, promoting youthful skin, cell health, elasticity, and flexibility. Other studies  have shown that proanthocyanidins help to protect the body from sun damage, to improve vision, to improve flexibility in joints, arteries, and body tissues such as the heart, and to improve blood circulation by strengthening capillaries, arteries, and veins. The most abundant phenolic compounds isolated from grape seed are catechins, epicatechin, procyanidin, and some dimers and trimers.  PMID: 14977436  [PubMed - indexed for MEDLINE] 

6. Free Radic Biol Med. 2002 Oct 15;33(8):1089-96.  Dermal wound healing properties of redox-active grape seed proanthocyanidins.  Khanna S, Venojarvi M, Roy S, Sharma N, Trikha P, Bagchi D, Bagchi M, Sen CK.  Department of Surgery, Heart and Lung Research Institute, The Ohio State University Medical Center, Columbus, OH 43210, USA. 

 Angiogenesis plays a central role in wound healing. Among many known growth factors, vascular endothelial growth factor (VEGF) is believed to be the most prevalent, efficacious, and long-term signal that is known to stimulate angiogenesis in wounds. The wound site is rich in oxidants, such as hydrogen peroxide, mostly contributed by neutrophils and macrophages. We proposed that oxidants in the wound microenvironment support the repair process. Proanthocyanidins or condensed tannins are a group of biologically active polyphenolic bioflavonoids that are synthesized by many plants. Previously we have reported that a grape seed proanthycyanidin extract containing 5000 ppm resveratrol (GSPE) potently upregulates oxidant and tumor necrosis factor-alpha inducible VEGF expression in human keratinocytes (Free Radic. Biol. Med. 31:38-42, 2001). Our current objective was to follow up on that finding and test  whether GSPE influences dermal wound healing in vivo. First, using a VEGF promoter-driven luciferase reporter construct we observed that the potentiating effect of GSPE on inducible VEGF expression is at the transcriptional level. The  reporter assay showed that GSPE alone is able to drive VEGF transcription. Next,  two dermal excisional wounds were inflicted on the back of mice and the wounds were left to heal by secondary intention. Topical application of GSPE accelerated wound contraction and closure. GSPE treatment was associated with a more well-defined hyperproliferative epithelial region, higher cell density, enhanced  deposition of connective tissue, and improved histological architecture. GSPE treatment also increased VEGF and tenascin expression in the wound edge tissue. Tissue glutathione oxidation and 4-hydroxynonenal immunostaining results supported that GSPE application enhanced the oxidizing environment at the wound site. Oxidants are known to promote both VEGF as well as tenascin expression. In  summary, our current study provides firm evidence to support that topical application of GSPE represents a feasible and productive approach to support dermal wound healing.  PMID: 12374620  [PubMed - indexed for MEDLINE] 

5. Ann N Y Acad Sci. 2002 May;957:239-49.  Oxygen, oxidants, and antioxidants in wound healing: an emerging paradigm.  Sen CK, Khanna S, Gordillo G, Bagchi D, Bagchi M, Roy S.  Laboratory of Molecular Medicine, Dorothy M. Davis Heart and Lung Research Institute, Department of Surgery (CMIS), The Ohio State University Medical Center, Columbus, Ohio 43210, USA. 

 Disrupted vasculature and high energy-demand by regenerating tissue results in wound hypoxia. Wound repair may be facilitated by oxygen therapy. Evidence supporting the mode of action of hyperbaric oxygen in promoting wound healing is  sketchy, however. Topical oxygen therapy involves local administration of pure oxygen. The advantages of topical oxygen therapy include low cost, the lack of systemic oxygen toxicity, and possibility of home treatment. While this modality  of wound care is of outstanding interest, it clearly lacks the support of mechanism-oriented studies. The search for mechanisms by which oxygen supports wound healing has now taken another step. Respiratory burst-derived oxidants support healing. Oxidants serve as cellular messengers to promote healing. Although this information is of outstanding significance to the practice of oxygen therapy, it remains largely unexplored. The search for "natural remedies"  has drawn attention to herbals. Proanthocyanidins or condensed tannins are a group of biologically active polyphenolic bioflavonoids that are synthesized by many plants. Proanthocyanidins and other tannins facilitate wound healing. A combination of grape seed proanthocyanidin extract and resveratrol facilitates inducible VEGF expression, a key element supporting wound angiogenesis. Strategies to manipulate the redox environment in the wound are likely to be of outstanding significance in wound healing.  PMID: 12074976  [PubMed - indexed for MEDLINE]  

4. Toxicology. 2000 Aug 7;148(2-3):187-97.  Free radicals and grape seed proanthocyanidin extract: importance in human health and disease prevention.  Bagchi D, Bagchi M, Stohs SJ, Das DK, Ray SD, Kuszynski CA, Joshi SS, Pruess HG.  Department of Pharmaceutical and Administrative Sciences, Creighton University School of Pharmacy & Allied Health Professions, 2500 California Plaza, Omaha, NE  68178, USA. 

 Free radicals have been implicated in over a hundred disease conditions in humans, including arthritis, hemorrhagic shock, atherosclerosis, advancing age, ischemia and reperfusion injury of many organs, Alzheimer and Parkinson's disease, gastrointestinal dysfunctions, tumor promotion and carcinogenesis, and AIDS. Antioxidants are potent scavengers of free radicals and serve as inhibitors of neoplastic processes. A large number of synthetic and natural antioxidants have been demonstrated to induce beneficial effects on human health and disease prevention. However, the structure-activity relationship, bioavailability and therapeutic efficacy of the antioxidants differ extensively. Oligomeric proanthocyanidins, naturally occurring antioxidants widely available in fruits, vegetables, nuts, seeds, flowers and bark, have been reported to possess a broad  spectrum of biological, pharmacological and therapeutic activities against free radicals and oxidative stress. We have assessed the concentration- or dose-dependent free radical scavenging ability of a novel IH636 grape seed proanthocyanidin extract (GSPE) both in vitro and in vivo models, and compared the free radical scavenging ability of GSPE with vitamins C, E and beta-carotene. These experiments demonstrated that GSPE is highly bioavailable and provides significantly greater protection against free radicals and free radical-induced lipid peroxidation and DNA damage than vitamins C, E and beta-carotene. GSPE was  also shown to demonstrate cytotoxicity towards human breast, lung and gastric adenocarcinoma cells, while enhancing the growth and viability of normal human gastric mucosal cells. The comparative protective effects of GSPE, vitamins C and E were examined on tobacco-induced oxidative stress and apoptotic cell death in human oral keratinocytes. Oxidative tissue damage was determined by lipid peroxidation and DNA fragmentation, while apoptotic cell death was assessed by flow cytometry. GSPE provided significantly better protection as compared to vitamins C and E, singly and in combination. GSPE also demonstrated excellent protection against acetaminophen overdose-induced liver and kidney damage by regulating bcl-X(L) gene, DNA damage and presumably by reducing oxidative stress. GSPE demonstrated excellent protection against myocardial ischemia-reperfusion injury and myocardial infarction in rats. GSPE was also shown to upregulate bcl(2) gene and downregulate the oncogene c-myc. Topical application of GSPE enhances sun protection factor in human volunteers, as well as supplementation of GSPE ameliorates chronic pancreatitis in humans. These results demonstrate that GSPE provides excellent protection against oxidative stress and free radical-mediated tissue injury.  PMID: 10962138  [PubMed - indexed for MEDLINE]  

3. Chem Biol Interact. 2000 Jun 15;127(1):45-59.  Inhibition of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse skin ornithine decarboxylase and protein kinase C by polyphenolics from grapes.  Bomser J, Singletary K, Meline B.  Department of Food Science and Human Nutrition, University of Illinois, 905 South Goodwin Avenue, 467 Bevier Hall, 61801, Urbana, IL, USA. 

 Ornithine decarboxylase is the rate-limiting enzyme in the biosynthesis of polyamines, which are believed to play an essential role in diverse biological processes including cell proliferation and differentiation. We have previously reported [J. Bomser, K. Singletary, M. Wallig, M. Smith, Inhibition of TPA-induced tumor promotion in CD-1 mouse epidermis by a polyphenolic fraction from grape seeds, Cancer Letters 135 (1999) 151-157] that pre-application of a grape polyphenolic fraction (GPF) to mouse skin epidermis inhibits 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ornithine decarboxylase (ODC)  activity, as well as 7, 12-dimethylbenz[a]anthracene (DMBA)-initiated, TPA-promoted mouse skin tumorigenesis. The present studies were designed to further characterize the effect of time and dose of application of GPF on TPA-induced ODC activity and protein expression, and on protein kinase C activity in mouse skin epidermis. In addition, the effect of GPF on ODC kinetics in vitro  was examined. Application of 5, 10, and 20 mg of GPF 20 min prior to treatment with TPA resulted in a significant decrease in epidermal ODC activity of 54, 53,  90%, respectively, compared with controls. Yet, ODC protein levels (Western blot) in the 10 and 20 mg GPF groups were significantly increased by 1.8 and 1.9-fold,  respectively, compared with controls. A similar response was observed with the ODC inhibitor 2-difluoromethylornithine (DFMO), which served as a positive control. Application of grape polyphenolics (20 mg) at 60 and 30 min prior to treatment with TPA inhibited ODC activity by 62 and 68%, respectively, compared with controls (P<0.05). In contrast, application of grape polyphenolics (20 mg) at 60, 120 and 240 min after treatment with TPA resulted in no significant changes in ODC activity. A similar increase in epidermal ODC protein was observed in these GPF-treated animals, similar to that observed when GPF application preceded TPA. When applied to mouse skin prior to TPA, GPF was associated with a  decrease in subsequent PKC activity compared with controls at 10 and 30 min following TPA treatment. The GPF-associated decrease in PKC activity preceded the decrease in ODC activity. In a separate in vitro study, kinetic analyses indicated that GPF is a competitive inhibitor of ODC activity. Collectively these data suggest that the grape polyphenolic fraction is effective as an inhibitor of ODC activity when applied before TPA, and that the magnitude of inhibition is independent of epidermal ODC protein content. In addition, GPF is a competitive inhibitor of ODC activity in vitro. The decrease in TPA-induced ODC activity due  to GPF treatment is preceded by an inhibition of TPA-induced PKC activity. Thus,  the polyphenolic fraction from grapes warrants further examination as a skin cancer chemopreventive agent that interferes with cellular events associated with TPA promotion.  PMID: 10903418  [PubMed - indexed for MEDLINE]  

2. Carcinogenesis. 1999 Sep;20(9):1737-45.  Anti-tumor-promoting activity of a polyphenolic fraction isolated from grape seeds in the mouse skin two-stage initiation-promotion protocol and identification of procyanidin B5-3'-gallate as the most effective antioxidant constituent.  Zhao J, Wang J, Chen Y, Agarwal R.  Center for Cancer Causation and Prevention, AMC Cancer Research Center, Denver, CO 80214, USA. 

 Procyanidins present in grape seeds are known to exert anti-inflammatory, anti-arthritic and anti-allergic activities, prevent skin aging, scavenge oxygen  free radicals and inhibit UV radiation-induced peroxidation activity. Since most  of these events are associated with the tumor promotion stage of carcinogenesis,  these studies suggest that grape seed polyphenols and the procyanidins present therein could be anticarcinogenic and/or anti-tumor-promoting agents. Therefore,  we assessed the anti-tumor-promoting effect of a polyphenolic fraction isolated from grape seeds (GSP) employing the 7,12-dimethylbenz[a]anthracene (DMBA)-initiated and 12-O-tetradecanoylphorbol 13-acetate (TPA)-promoted SENCAR mouse skin two-stage carcinogenesis protocol as a model system. Following tumor initiation with DMBA, topical application of GSP at doses of 0.5 and 1.5 mg/mouse/application to the dorsal initiated mouse skin resulted in a highly significant inhibition of TPA tumor promotion. The observed anti-tumor-promoting  effects of GSP were dose dependent and were evident in terms of a reduction in tumor incidence (35 and 60% inhibition), tumor multiplicity (61 and 83% inhibition) and tumor volume (67 and 87% inhibition) at both 0.5 and 1.5 mg GSP,  respectively. Based on these results, we directed our efforts to separate and identify the individual polyphenols present in GSP and assess their antioxidant activity in terms of inhibition of epidermal lipid peroxidation. Employing HPLC followed by comparison with authentic standards for retention times in HPLC profiles, physiochemical properties and spectral analysis, nine individual polyphenols were identified as catechin, epicatechin, procyanidins B1-B5 and C1 and procyanidin B5-3'-gallate. Five of these individual polyphenols with evident  structural differences, namely catechin, procyanidin B2, procyanidin B5, procyanidin C1 and procyanidin B5-3'-gallate, were assessed for antioxidant activity. All of them significantly inhibited epidermal lipid peroxidation, albeit to different levels. A structure-activity relationship study showed that with an increase in the degree of polymerization in polyphenol structure, the inhibitory potential towards lipid peroxidation increased. In addition, the position of linkage between inter-flavan units also influences lipid peroxidation activity; procyanidin isomers with a 4-6 linkage showed stronger inhibitory activity than isomers with a 4-8 linkage. A sharp increase in the inhibition of epidermal lipid peroxidation was also evident when a gallate group was linked at  the 3'-hydroxy position of a procyanidin dimer. Procyanidin B5-3'-gallate showed  the most potent antioxidant activity with an IC(50) of 20 microM in an epidermal  lipid peroxidation assay. Taken together, for the first time these results show that grape seed polyphenols possess high anti-tumor-promoting activity due to the strong antioxidant effect of procyanidins present therein. In summary, grape seed polyphenols in general, and procyanidin B5-3'-gallate in particular, should be studied in more detail to be developed as cancer chemopreventive and/or anticarcinogenic agents.  PMID: 10469619  [PubMed - indexed for MEDLINE] 

1. Cancer Lett. 1999 Jan 29;135(2):151-7.  Inhibition of TPA-induced tumor promotion in CD-1 mouse epidermis by a polyphenolic fraction from grape seeds.  Bomser JA, Singletary KW, Wallig MA, Smith MA.  Department of Food Science and Human Nutrition, University of Illinois, Urbana 61801, USA. 

 The anti-tumor promoting activity of a polyphenolic fraction from grape seeds (GSP) was examined in CD-1 mouse skin epidermis. Specifically, the ability of this fraction to inhibit 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced tumor promotion and two markers of promotion in mouse skin, ornithine decarboxylase (ODC) and myeloperoxidase (MPO) activities, was evaluated. Pretreatment of mouse  skin with 5, 10, 20 and 30 mg of GSP resulted in a dose-dependent reduction in TPA-induced epidermal ODC activity of 27, 37, 48 and 70%, respectively, compared  to controls. In addition, pretreatment of mouse skin with 1, 5, 10 and 20 mg of GSP resulted in a significant 43, 39, 54 and 73% inhibition of MPO activity, respectively, compared to controls. In 7,12-dimethylbenz[a]anthracene (DMBA)-initiated CD-1 mice, biweekly treatment of mouse skin with 5, 10, and 20 mg of GSP 20 min prior to TPA application resulted in a 30, 40, and 60% inhibition of final skin tumor incidence, respectively, compared to controls. In  addition, the final number of tumors per mouse in the 5, 10 and 20 mg GSP-treated animals was decreased 63, 51, and 94%, respectively, compared to controls. These  studies indicate that GSP possesses anti-tumor promoting activity when applied to CD-1 mouse skin prior to treatment with TPA. The mechanism of this tumor inhibition is due, in part, to a GSP-associated inhibition of TPA-induced epidermal ODC and MPO activities. Thus, GSP warrants further evaluation as a skin cancer chemopreventative agent.  PMID: 10096423  [PubMed - indexed for MEDLINE]   

Research has shown Grape Seed Proanthocyanidins to be effective as: an antioxidant, an anti-allergenic, and an anti-inflammatory. It also promotes capillary health while increasing skin elasticity and providing sun damage protection/repair. You may also find it used in wound therapy recipes.
Grape Seed Proanthocyanidins research

DISCLAIMER:Any statements about products sold by BulkActives have not been evaluated by the FDA.  Products sold by BulkActives are not intended to be used as nutritional supplements. Products sold by BulkActives are not intended to diagnose, treat, cure, or prevent any disease.

 BulkActives: ingredients for DIY skin care and cosmetics
Grape seed
proanthocyanidins 95%

Grape Seed Proanthocyanidins in skin care:


  • antioxidant
  • anti-allergenic
  • anti-inflammatory
  • capillary health
  • increase skin elasticity
  • sun damage protection
  • sun damage repair
  • wound healing support