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      Pomegranate Peel Extract Prevents Bone Loss in a Preclinical Model of Osteoporosis and Stimulates Osteoblastic Differentiation in Vitro

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          Abstract

          The nutritional benefits of pomegranate have attracted great scientific interest. The pomegranate, including the pomegranate peel, has been used worldwide for many years as a fruit with medicinal activity, mostly antioxidant properties. Among chronic diseases, osteoporosis, which is associated with bone remodelling impairment leading to progressive bone loss, could eventually benefit from antioxidant compounds because of the involvement of oxidative stress in the pathogenesis of osteopenia. In this study, with in vivo and ex vivo experiments, we investigated whether the consumption of pomegranate peel extract (PGPE) could limit the process of osteopenia. We demonstrated that in ovariectomized (OVX) C57BL/6J mice, PGPE consumption was able to significantly prevent the decrease in bone mineral density (−31.9%; p < 0.001 vs. OVX mice) and bone microarchitecture impairment. Moreover, the exposure of RAW264.7 cells to serum harvested from mice that had been given a PGPE-enriched diet elicited reduced osteoclast differentiation and bone resorption, as shown by the inhibition of the major osteoclast markers. In addition, PGPE appeared to substantially stimulate osteoblastic MC3T3-E1 alkaline phosphatase (ALP) activity at day 7, mineralization at day 21 and the transcription level of osteogenic markers. PGPE may be effective in preventing the bone loss associated with ovariectomy in mice, and offers a promising alternative for the nutritional management of this disease.

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          Osteoporosis: now and the future.

          Osteoporosis is a common disease characterised by a systemic impairment of bone mass and microarchitecture that results in fragility fractures. With an ageing population, the medical and socioeconomic effect of osteoporosis, particularly postmenopausal osteoporosis, will increase further. A detailed knowledge of bone biology with molecular insights into the communication between bone-forming osteoblasts and bone-resorbing osteoclasts and the orchestrating signalling network has led to the identification of novel therapeutic targets. Novel treatment strategies have been developed that aim to inhibit excessive bone resorption and increase bone formation. The most promising novel treatments include: denosumab, a monoclonal antibody for receptor activator of NF-κB ligand, a key osteoclast cytokine; odanacatib, a specific inhibitor of the osteoclast protease cathepsin K; and antibodies against the proteins sclerostin and dickkopf-1, two endogenous inhibitors of bone formation. This overview discusses these novel therapies and explains their underlying physiology. Copyright © 2011 Elsevier Ltd. All rights reserved.
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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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              The ovariectomized rat model of postmenopausal bone loss.

              Dike Kalu (1991)
              An animal model of postmenopausal bone loss can be defined as a living animal in which spontaneous or induced bone loss due to ovarian hormone deficiency can be studied, and in which the characteristics of the bone loss and its sequalae resemble those found in postmenopausal women in one or more respects. Although in comparison to humans, the skeletal mass of rats remains stable for a protracted period during their lifespan, rats can be ovariectomized to make them sex-hormone deficient, and to stimulate the accelerated loss of bone that occurs in women following menopause. Ovariectomy induced bone loss in the rat and postmenopausal bone loss share many similar characteristics. These include: increased rate of bone turnover with resorption exceeding formation; and initial rapid phase of bone loss followed by a much slower phase; greater loss of cancellous than cortical bone; decreased intestinal absorption of calcium; some protection against bone loss by obesity; and similar skeletal response to therapy with estrogen, tamoxifen, bisphosphonates, parathyroid hormone, calcitonin and exercise. These wide-ranging similarities are strong evidence that the ovariectomized rat bone loss model is suitable for studying problems that are relevant to postmenopausal bone loss.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                11 November 2015
                November 2015
                : 7
                : 11
                : 9265-9284
                Affiliations
                [1 ]Unité de Nutrition Humaine, CRNH Auvergne, UMR 1019, INRA, F-63000 Clermont-Ferrand, France; mel.spilmont@ 123456gmail.com (M.S.); laurent.leotoing@ 123456clermont.inra.fr (L.L.); marie-jeanne.davicco@ 123456clermont.inra.fr (M.-J.D.); Patrice.Lebecque@ 123456clermont.inra.fr (P.L.); yohann.wittrant@ 123456clermont.inra.fr (Y.W.)
                [2 ]Unité de Nutrition Humaine, Université d'Auvergne, Clermont Université, BP 10448, F-63000 Clermont-Ferrand, France
                [3 ]GREENTECH SA Biopôle Clermont-Limagne, F-63360 Saint-Beauzire, France; laurent.rios@ 123456vetagro-sup.fr
                [4 ]Imagerie Moléculaire et Thérapie Vectorisée, Université d'Auvergne, Clermont Université, UMR 990, INSERM, BP 10448, F-63000 Clermont-Ferrand, France; elisabeth.noirault@ 123456inserm.fr
                [5 ]Laboratoire d'Ingénierie Ostéo-Articulaire et Dentaire-LIOAD, Université de Nantes, UMR 791, INSERM, F-44042 Nantes, France; paul.pilet@ 123456univ-nantes.fr
                Author notes
                [* ]Correspondence: veronique.coxam@ 123456clermont.inra.fr ; Tel.: +33-047-362-4784
                Article
                nutrients-07-05465
                10.3390/nu7115465
                4663593
                26569295
                d6abd7ac-6004-4a6a-97fa-9a4cd900e446
                © 2015 by the authors; licensee MDPI, Basel, Switzerland.

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

                History
                : 21 September 2015
                : 14 October 2015
                Categories
                Article

                Nutrition & Dietetics
                pomegranate peel extract,nutritional prevention,bone health,cell lines,animal model

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