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      Bioaccessible Raspberry Extracts Enriched in Ellagitannins and Ellagic Acid Derivatives Have Anti-Neuroinflammatory Properties

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          Abstract

          Chronic neuroinflammation associated with neurodegenerative disorders has been reported to be prevented by dietary components. Particularly, dietary (poly)phenols have been identified as having anti-inflammatory and neuroprotective actions, and their ingestion is considered a major preventive factor for such disorders. To assess the relation between (poly)phenol classes and their bioactivity, we used five different raspberry genotypes, which were markedly different in their (poly)phenol profiles within a similar matrix. In addition, gastro-intestinal bio-accessible fractions were produced, which simulate the (poly)phenol metabolites that may be absorbed after digestion, and evaluated for anti-inflammatory potential using LPS-stimulated microglia. Interestingly, the fraction from genotype 2J19 enriched in ellagitannins, their degradation products and ellagic acid, attenuated pro-inflammatory markers and mediators CD40, NO, TNF-α, and intracellular superoxide via NF-κB, MAPK and NFAT pathways. Importantly, it also increased the release of the anti-inflammatory cytokine IL-10. These effects contrasted with fractions richer in anthocyanins, suggesting that ellagitannins and its derivatives are major anti-inflammatory (poly)phenols and promising compounds to alleviate neuroinflammation

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          Most cited references51

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          NF-κB signaling in inflammation

          The transcription factor NF-κB regulates multiple aspects of innate and adaptive immune functions and serves as a pivotal mediator of inflammatory responses. NF-κB induces the expression of various pro-inflammatory genes, including those encoding cytokines and chemokines, and also participates in inflammasome regulation. In addition, NF-κB plays a critical role in regulating the survival, activation and differentiation of innate immune cells and inflammatory T cells. Consequently, deregulated NF-κB activation contributes to the pathogenic processes of various inflammatory diseases. In this review, we will discuss the activation and function of NF-κB in association with inflammatory diseases and highlight the development of therapeutic strategies based on NF-κB inhibition.
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            p38 MAP-kinases pathway regulation, function and role in human diseases.

            Mammalian p38 mitogen-activated protein kinases (MAPKs) are activated by a wide range of cellular stresses as well as in response to inflammatory cytokines. There are four members of the p38MAPK family (p38alpha, p38beta, p38gamma and p38delta) which are about 60% identical in their amino acid sequence but differ in their expression patterns, substrate specificities and sensitivities to chemical inhibitors such as SB203580. A large body of evidences indicates that p38MAPK activity is critical for normal immune and inflammatory response. The p38MAPK pathway is a key regulator of pro-inflammatory cytokines biosynthesis at the transcriptional and translational levels, which makes different components of this pathway potential targets for the treatment of autoimmune and inflammatory diseases. However, recent studies have shed light on the broad effect of p38MAPK activation in the control of many other aspects of the physiology of the cell, such as control of cell cycle or cytoskeleton remodelling. Here we focus on these emergent roles of p38MAPKs and their implication in different pathologies.
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              Neuroinflammation and M2 microglia: the good, the bad, and the inflamed

              The concept of multiple macrophage activation states is not new. However, extending this idea to resident tissue macrophages, like microglia, has gained increased interest in recent years. Unfortunately, the research on peripheral macrophage polarization does not necessarily translate accurately to their central nervous system (CNS) counterparts. Even though pro- and anti-inflammatory cytokines can polarize microglia to distinct activation states, the specific functions of these states is still an area of intense debate. This review examines the multiple possible activation states microglia can be polarized to. This is followed by a detailed description of microglial polarization and the functional relevance of this process in both acute and chronic CNS disease models described in the literature. Particular attention is given to utilizing M2 microglial polarization as a potential therapeutic option in treating diseases.
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                Author and article information

                Journal
                Antioxidants (Basel)
                Antioxidants (Basel)
                antioxidants
                Antioxidants
                MDPI
                2076-3921
                10 October 2020
                October 2020
                : 9
                : 10
                : 970
                Affiliations
                [1 ]Instituto de Biologia Experimental e Tecnológica (iBET), apartado 12, 2781-901 Oeiras, Portugal; ggarcia@ 123456campus.ul.pt (G.G.); mtpais@ 123456igc.gulbenkian.pt (T.F.P.)
                [2 ]ITQB, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, 2780-157 Oeiras, Portugal; paula.pn2@ 123456gmail.com
                [3 ]Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal
                [4 ]Instituto Gulbenkian de Ciência (IGC), Rua Quinta Grande, 2780-156 Oeiras, Portugal
                [5 ]Instituto Politécnico de Santarém, Escola Superior Agrária, Qta do Galinheiro, 2001-904 Santarém, Portugal
                [6 ]Life Quality Research Centre (CIEQV), IPSantarém/IPLeiria, 2040-413 Rio Maior, Portugal
                [7 ]Plant Biochemistry and Food Quality Group, Environmental and Biochemical Science, The James Hutton Institute, Dundee DD2 5DA, Scotland, UK; Gary.Dobson@ 123456hutton.ac.uk (G.D.); gordon.mcdougall@ 123456hutton.ac.uk (G.J.M.); derek.Stewart@ 123456hutton.ac.uk (D.S.)
                [8 ]School of Engineering and Physical Sciences, Institute of Mechanical, Process and Energy Engineering, Heriot-Watt University, Edinburg EH14 4AS, Scotland, UK
                [9 ]CEDOC, Chronic Diseases Research Centre, NOVA Medical School//Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Campo dos Mártires da Pátria, 130, 1169-056 Lisboa, Portugal
                Author notes
                Author information
                https://orcid.org/0000-0001-5526-5362
                https://orcid.org/0000-0002-8855-4395
                https://orcid.org/0000-0001-6379-1768
                https://orcid.org/0000-0001-9926-4206
                https://orcid.org/0000-0002-2285-0124
                https://orcid.org/0000-0001-9838-4265
                https://orcid.org/0000-0002-5809-1924
                Article
                antioxidants-09-00970
                10.3390/antiox9100970
                7600793
                33050384
                361b595c-1a96-409a-9324-06401f89cfda
                © 2020 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
                : 22 September 2020
                : 07 October 2020
                Categories
                Article

                polyphenol metabolites,gastro-intestinal digestion,neuroinflammation,microglia,nf-kappab

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