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      Grape Seeds Proanthocyanidins: An Overview of In Vivo Bioactivity in Animal Models

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          Abstract

          Over the last decade, proanthocyanidins (PACs) are attracting attention not only from the food industry but also from public health organizations due to their health benefits. It is well-known that grapes are a good source of PACs and for that reason, the industry is also focused on grape by-products identification and bioactivity evaluation. Grape seeds extract (GSPE) is a rich source of PACs, mainly composed of monomeric catechin and epicatechin, gallic acid and polymeric and oligomeric proanthocyanidins. Thus, this review encompasses the state-of-art structure and the most recent evidence about the impact of GSPE on chronic diseases, with a focus on oxidative stress, inflammation and metabolic syndrome (MeS)-related disorders such as obesity, diabetes and cardiovascular risk disease in vivo to offer new perspectives in the field that allow further research. Despite the controversial results, is undeniable that PACs from grape seeds are highly antioxidants, thus, the capacity of GSPE to improve oxidative stress might mediate the inflammation process and the progress of MeS-related pathologies. However, further well-design animal studies with standardized dosages and GSPE composition are necessary to shed light into the cause-effect relationship in a more accurate way to later allow a deeper study of the effect of GSPE in humans.

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          Oxidative stress and metabolic syndrome.

          Metabolic syndrome is a collection of cardiometabolic risk factors that includes obesity, insulin resistance, hypertension and dyslipidemia. Although there has been significant debate regarding the criteria and concept of the syndrome, this clustering of risk factors is unequivocally linked to an increased risk of developing type 2 diabetes and cardiovascular disease. Metabolic syndrome is often characterized by oxidative stress, a condition in which an imbalance results between the production and inactivation of reactive oxygen species. Reactive oxygen species can best be described as double-edged swords; while they play an essential role in multiple physiological systems, under conditions of oxidative stress, they contribute to cellular dysfunction. Oxidative stress is thought to play a major role in the pathogenesis of a variety of human diseases, including atherosclerosis, diabetes, hypertension, aging, Alzheimer's disease, kidney disease and cancer. The purpose of this review is to discuss the role of oxidative stress in metabolic syndrome and its major clinical manifestations (namely coronary artery disease, hypertension and diabetes). It will also highlight the effects of lifestyle modification in ameliorating oxidative stress in metabolic syndrome. Discussion will be limited to human data.
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            Free radicals and grape seed proanthocyanidin extract: importance in human health and disease prevention.

            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.
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              Proanthocyanidins: A comprehensive review

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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                12 October 2019
                October 2019
                : 11
                : 10
                : 2435
                Affiliations
                [1 ]Department of Nutrition and Food Science, University of Granada, Campus of Cartuja, 18071 Granada, Spain
                [2 ]Institute of Nutrition and Food Technology (INYTA) ‘José Mataix’, Biomedical Research Centre, University of Granada, Avenida del Conocimiento s/n, E-18071 Granada, Spain
                Author notes
                [* ]Correspondence: vitoverardo@ 123456ugr.es ; Tel.: +34-958-243866
                Author information
                https://orcid.org/0000-0002-7233-6481
                https://orcid.org/0000-0002-2841-7743
                https://orcid.org/0000-0003-0723-5163
                Article
                nutrients-11-02435
                10.3390/nu11102435
                6835351
                31614852
                58f7f99b-50b1-4f82-ac3a-b917889a5479
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 03 September 2019
                : 02 October 2019
                Categories
                Review

                Nutrition & Dietetics
                grape seed by-products,proanthocyanidins,metabolic syndrome,chronic diseases,in vivo animal studies

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