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      Molecular signaling mechanisms behind polyphenol-induced bone anabolism

      review-article
      Phytochemistry Reviews
      Springer Netherlands
      Anti-inflammation, Antioxidant, Bone disease, Pathway, Polyphenols

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          Abstract

          For millennia, in the different cultures all over the world, plants have been extensively used as a source of therapeutic agents with wide-ranging medicinal applications, thus becoming part of a rational clinical and pharmacological investigation over the years. As bioactive molecules, plant-derived polyphenols have been demonstrated to exert many effects on human health by acting on different biological systems, thus their therapeutic potential would represent a novel approach on which natural product-based drug discovery and development could be based in the future. Many reports have provided evidence for the benefits derived from the dietary supplementation of polyphenols in the prevention and treatment of osteoporosis. Polyphenols are able to protect the bone, thanks to their antioxidant properties, as well as their anti-inflammatory actions by involving diverse signaling pathways, thus leading to bone anabolic effects and decreased bone resorption. This review is meant to summarize the research works performed so far, by elucidating the molecular mechanisms of action of polyphenols in a bone regeneration context, aiming at a better understanding of a possible application in the development of medical devices for bone tissue regeneration.

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          Most cited references376

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          Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta.

          The rat, mouse and human estrogen receptor (ER) exists as two subtypes, ER alpha and ER beta, which differ in the C-terminal ligand-binding domain and in the N-terminal transactivation domain. In this study, we investigated the estrogenic activity of environmental chemicals and phytoestrogens in competition binding assays with ER alpha or ER beta protein, and in a transient gene expression assay using cells in which an acute estrogenic response is created by cotransfecting cultures with recombinant human ER alpha or ER beta complementary DNA (cDNA) in the presence of an estrogen-dependent reporter plasmid. Saturation ligand-binding analysis of human ER alpha and ER beta protein revealed a single binding component for [3H]-17beta-estradiol (E2) with high affinity [dissociation constant (Kd) = 0.05 - 0.1 nM]. All environmental estrogenic chemicals [polychlorinated hydroxybiphenyls, dichlorodiphenyltrichloroethane (DDT) and derivatives, alkylphenols, bisphenol A, methoxychlor and chlordecone] compete with E2 for binding to both ER subtypes with a similar preference and degree. In most instances the relative binding affinities (RBA) are at least 1000-fold lower than that of E2. Some phytoestrogens such as coumestrol, genistein, apigenin, naringenin, and kaempferol compete stronger with E2 for binding to ER beta than to ER alpha. Estrogenic chemicals, as for instance nonylphenol, bisphenol A, o, p'-DDT and 2',4',6'-trichloro-4-biphenylol stimulate the transcriptional activity of ER alpha and ER beta at concentrations of 100-1000 nM. Phytoestrogens, including genistein, coumestrol and zearalenone stimulate the transcriptional activity of both ER subtypes at concentrations of 1-10 nM. The ranking of the estrogenic potency of phytoestrogens for both ER subtypes in the transactivation assay is different; that is, E2 > zearalenone = coumestrol > genistein > daidzein > apigenin = phloretin > biochanin A = kaempferol = naringenin > formononetin = ipriflavone = quercetin = chrysin for ER alpha and E2 > genistein = coumestrol > zearalenone > daidzein > biochanin A = apigenin = kaempferol = naringenin > phloretin = quercetin = ipriflavone = formononetin = chrysin for ER beta. Antiestrogenic activity of the phytoestrogens could not be detected, except for zearalenone which is a full agonist for ER alpha and a mixed agonist-antagonist for ER beta. In summary, while the estrogenic potency of industrial-derived estrogenic chemicals is very limited, the estrogenic potency of phytoestrogens is significant, especially for ER beta, and they may trigger many of the biological responses that are evoked by the physiological estrogens.
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            Antioxidant and prooxidant properties of flavonoids.

            The interest in possible health benefits of flavonoids has increased owing to their potent antioxidant and free radical scavenging activities observed in vitro. Nevertheless, the antioxidant efficacy of flavonoids in vivo is less documented and their prooxidant properties have been actually described in vivo. Due to their prooxidant properties, they are able to cause oxidative damage by reacting with various biomolecules, such as lipids, proteins and DNA. Hence, the aim of this review is to discuss both the antioxidant and prooxidant effects of flavonoids. Copyright © 2011 Elsevier B.V. All rights reserved.
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              Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis.

              The adult skeleton regenerates by temporary cellular structures that comprise teams of juxtaposed osteoclasts and osteoblasts and replace periodically old bone with new. A considerable body of evidence accumulated during the last decade has shown that the rate of genesis of these two highly specialized cell types, as well as the prevalence of their apoptosis, is essential for the maintenance of bone homeostasis; and that common metabolic bone disorders such as osteoporosis result largely from a derangement in the birth or death of these cells. The purpose of this article is 3-fold: 1) to review the role and the molecular mechanism of action of regulatory molecules, such as cytokines and hormones, in osteoclast and osteoblast birth and apoptosis; 2) to review the evidence for the contribution of changes in bone cell birth or death to the pathogenesis of the most common forms of osteoporosis; and 3) to highlight the implications of bone cell birth and death for a better understanding of the mechanism of action and efficacy of present and future pharmacotherapeutic agents for osteoporosis.
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                Author and article information

                Contributors
                etorre@nobilbio.it
                Journal
                Phytochem Rev
                Phytochem Rev
                Phytochemistry Reviews
                Springer Netherlands (Dordrecht )
                1568-7767
                1572-980X
                31 August 2017
                31 August 2017
                2017
                : 16
                : 6
                : 1183-1226
                Affiliations
                Nobil Bio Ricerche srl, Via Valcastellana, 26, 14037 Portacomaro, AT Italy
                Author information
                http://orcid.org/0000-0003-3878-2274
                Article
                9529
                10.1007/s11101-017-9529-x
                5696504
                e69ac18c-852c-4ac4-9733-de1eeb55fd05
                © The Author(s) 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 27 January 2017
                : 20 August 2017
                Categories
                Article
                Custom metadata
                © Springer Science+Business Media B.V., part of Springer Nature 2017

                Biochemistry
                anti-inflammation,antioxidant,bone disease,pathway,polyphenols
                Biochemistry
                anti-inflammation, antioxidant, bone disease, pathway, polyphenols

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