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      Mixed Pro- and Anti-Oxidative Effects of Pomegranate Polyphenols in Cultured Cells

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          Abstract

          In recent years, the number of scientific papers concerning pomegranate ( Punica granatum L.) and its health properties has increased greatly, and there is great potential for the use of bioactive-rich pomegranate extracts as ingredients in functional foods and nutraceuticals. To translate this potential into effective strategies it is essential to further elucidate the mechanisms of the reported bioactivity. In this study HepG2 cells were supplemented with a pomegranate fruit extract or with the corresponding amount of pure punicalagin, and then subjected to an exogenous oxidative stress. Overall, upon the oxidative stress the gene expression and activity of the main antioxidant enzymes appeared reduced in supplemented cells, which were more prone to the detrimental effects than unsupplemented ones. No differences were detected between cells supplemented with the pomegranate juice or the pure punicalagin. Although further studies are needed due to the gaps existing between in vitro and in vivo studies, our results suggest caution in the administration of high concentrations of nutraceutical molecules, particularly when they are administered in concentrated form.

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          Most cited references27

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          Antioxidant activity applying an improved ABTS radical cation decolorization assay.

          A method for the screening of antioxidant activity is reported as a decolorization assay applicable to both lipophilic and hydrophilic antioxidants, including flavonoids, hydroxycinnamates, carotenoids, and plasma antioxidants. The pre-formed radical monocation of 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS*+) is generated by oxidation of ABTS with potassium persulfate and is reduced in the presence of such hydrogen-donating antioxidants. The influences of both the concentration of antioxidant and duration of reaction on the inhibition of the radical cation absorption are taken into account when determining the antioxidant activity. This assay clearly improves the original TEAC assay (the ferryl myoglobin/ABTS assay) for the determination of antioxidant activity in a number of ways. First, the chemistry involves the direct generation of the ABTS radical monocation with no involvement of an intermediary radical. Second, it is a decolorization assay; thus the radical cation is pre-formed prior to addition of antioxidant test systems, rather than the generation of the radical taking place continually in the presence of the antioxidant. Hence the results obtained with the improved system may not always be directly comparable with those obtained using the original TEAC assay. Third, it is applicable to both aqueous and lipophilic systems.
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            Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processing.

            The antioxidant activity of pomegranate juices was evaluated by four different methods (ABTS, DPPH, DMPD, and FRAP) and compared to those of red wine and a green tea infusion. Commercial pomegranate juices showed an antioxidant activity (18-20 TEAC) three times higher than those of red wine and green tea (6-8 TEAC). The activity was higher in commercial juices extracted from whole pomegranates than in experimental juices obtained from the arils only (12-14 TEAC). HPLC-DAD and HPLC-MS analyses of the juices revealed that commercial juices contained the pomegranate tannin punicalagin (1500-1900 mg/L) while only traces of this compound were detected in the experimental juice obtained from arils in the laboratory. This shows that pomegranate industrial processing extracts some of the hydrolyzable tannins present in the fruit rind. This could account for the higher antioxidant activity of commercial juices compared to the experimental ones. In addition, anthocyanins, ellagic acid derivatives, and hydrolyzable tannins were detected and quantified in the pomegranate juices.
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              Punica granatum (pomegranate) and its potential for prevention and treatment of inflammation and cancer.

              The last 7 years have seen over seven times as many publications indexed by Medline dealing with pomegranate and Punica granatum than in all the years preceding them. Because of this, and the virtual explosion of interest in pomegranate as a medicinal and nutritional product that has followed, this review is accordingly launched. The pomegranate tree, Punica granatum, especially its fruit, possesses a vast ethnomedical history and represents a phytochemical reservoir of heuristic medicinal value. The tree/fruit can be divided into several anatomical compartments: (1) seed, (2) juice, (3) peel, (4) leaf, (5) flower, (6) bark, and (7) roots, each of which has interesting pharmacologic activity. Juice and peels, for example, possess potent antioxidant properties, while juice, peel and oil are all weakly estrogenic and heuristically of interest for the treatment of menopausal symptoms and sequellae. The use of juice, peel and oil have also been shown to possess anticancer activities, including interference with tumor cell proliferation, cell cycle, invasion and angiogenesis. These may be associated with plant based anti-inflammatory effects, The phytochemistry and pharmacological actions of all Punica granatum components suggest a wide range of clinical applications for the treatment and prevention of cancer, as well as other diseases where chronic inflammation is believed to play an essential etiologic role.
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                Author and article information

                Contributors
                Role: External Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                27 October 2014
                November 2014
                : 15
                : 11
                : 19458-19471
                Affiliations
                [1 ]Department of Agri-Food Sciences and Technologies, University of Bologna, Piazza Goidanich, 60-47521 Cesena (FC), Italy; E-Mails: filippo.dantuono@ 123456unibo.it (L.F.D.); alessandra.bordoni@ 123456unibo.it (A.B.)
                [2 ]Food & Health Programme, Institute of Food Research, Norwich Research Park, Norwich NR4 7UA, UK; E-Mails: paul.kroon@ 123456ifr.ac.uk (P.A.K.); shikha.saha@ 123456ifr.ac.uk (S.S.)
                [3 ]Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Via Altura, 3-40139 Bologna (BO), Italy; E-Mail: dario.debiase@ 123456unibo.it
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: francesca.danesi@ 123456unibo.it ; Tel.: +39-0547-338957; Fax: +39-0547-382348.
                Article
                ijms-15-19458
                10.3390/ijms151119458
                4264122
                25350111
                5ffb9306-9eae-4a51-9fd5-3f8cf1b26f4c
                © 2014 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 license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 30 July 2014
                : 09 October 2014
                : 21 October 2014
                Categories
                Article

                Molecular biology
                pomegranate,punicalagin,oxidative stress,antioxidant defenses,bioactives,hepg2 cells
                Molecular biology
                pomegranate, punicalagin, oxidative stress, antioxidant defenses, bioactives, hepg2 cells

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