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      Polyphenol Health Effects on Cardiovascular and Neurodegenerative Disorders: A Review and Meta-Analysis

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          Abstract

          Several studies have demonstrated that polyphenol-enriched diets may have beneficial effects against the development of degenerative diseases, including atherosclerosis and disorders affecting the central nervous system. This activity has been associated not only with antioxidant and anti-inflammatory properties, but also with additional mechanisms, such as the modulation of lipid metabolism and gut microbiota function. However, long-term studies on humans provided controversial results, making the prediction of polyphenol impact on health uncertain. The aim of this review is to provide an overview and critical analysis of the literature related to the effects of the principal dietary polyphenols on cardiovascular and neurodegenerative disorders. We critically considered and meta-analyzed randomized controlled clinical trials involving subjects taking polyphenol-based supplements. Although some polyphenols might improve specific markers of cardiovascular risk and cognitive status, many inconsistent data are present in literature. Therefore, definitive recommendations for the use of these compounds in the prevention of cardiovascular disease and cognitive decline are currently not applicable. Once pivotal aspects for the definition of polyphenol bioactivity, such as the characterization of pharmacokinetics and safety, are addressed, it will be possible to have a clear picture of the realistic potential of polyphenols for disease prevention.

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          Most cited references71

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          Effect of tea phenolics and their aromatic fecal bacterial metabolites on intestinal microbiota.

          Tea is rich in polyphenols and other phenolics that have been widely reported to have beneficial health effects. However, dietary polyphenols are not completely absorbed from the gastrointestinal tract and are metabolized by the gut microflora so that they and their metabolites may accumulate to exert physiological effects. In this study, we investigated the influence of the phenolic components of a tea extract and their aromatic metabolites upon bacterial growth. Fecal homogenates containing bacteria significantly catalyzed tea phenolics, including epicatechin, catechin, 3-O-methyl gallic acid, gallic acid and caffeic acid to generate aromatic metabolites dependent on bacterial species. Different strains of intestinal bacteria had varying degrees of growth sensitivity to tea phenolics and metabolites. Growth of certain pathogenic bacteria such as Clostridium perfringens, Clostridium difficile and Bacteroides spp. was significantly repressed by tea phenolics and their derivatives, while commensal anaerobes like Clostridium spp., Bifidobacterium spp. and probiotics such as Lactobacillus sp. were less severely affected. This indicates that tea phenolics exert significant effects on the intestinal environment by modulation of the intestinal bacterial population, probably by acting as metabolic prebiotics. Our observations provide further evidence for the importance of colonic bacteria in the metabolism, absorption and potential activity of phenolics in human health and disease. The bioactivity of different phenolics may play an important role in the maintenance of gastrointestinal health.
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            Regulation of inflammation and redox signaling by dietary polyphenols.

            Reactive oxygen species (ROS) play a key role in enhancing the inflammation through the activation of NF-kappaB and AP-1 transcription factors, and nuclear histone acetylation and deacetylation in various inflammatory diseases. Such undesired effects of oxidative stress have been found to be controlled by the antioxidant and/or anti-inflammatory effects of dietary polyphenols such as curcumin (diferuloylmethane, a principal component of turmeric) and resveratrol (a flavonoid found in red wine). The phenolic compounds in fruits, vegetables, tea and wine are mostly derivatives, and/or isomers of flavones, isoflavones, flavonols, catechins, tocopherols, and phenolic acids. Polyphenols modulate important cellular signaling processes such as cellular growth, differentiation and host of other cellular features. In addition, they modulate NF-kappaB activation, chromatin structure, glutathione biosynthesis, nuclear redox factor (Nrf2) activation, scavenge effect of ROS directly or via glutathione peroxidase activity and as a consequence regulate inflammatory genes in macrophages and lung epithelial cells. However, recent data suggest that dietary polyphenols can work as modifiers of signal transduction pathways to elicit their beneficial effects. The effects of polyphenols however, have been reported to be more pronounced in vitro using high concentrations which are not physiological in vivo. This commentary discusses the recent data on dietary polyphenols in the control of signaling and inflammation particularly during oxidative stress, their metabolism and bioavailability.
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              Antioxidant activity, total phenolics and flavonoids contents: Should we ban in vitro screening methods?

              As many studies are exploring the association between ingestion of bioactive compounds and decreased risk of non-communicable diseases, the scientific community continues to show considerable interest in these compounds. In addition, as many non-nutrients with putative health benefits are reducing agents, hydrogen donors, singlet oxygen quenchers or metal chelators, measurement of antioxidant activity using in vitro assays has become very popular over recent decades. Measuring concentrations of total phenolics, flavonoids, and other compound (sub)classes using UV/Vis spectrophotometry offers a rapid chemical index, but chromatographic techniques are necessary to establish structure-activity. For bioactive purposes, in vivo models are required or, at the very least, methods that employ distinct mechanisms of action (i.e., single electron transfer, transition metal chelating ability, and hydrogen atom transfer). In this regard, better understanding and application of in vitro screening methods should help design of future research studies on 'bioactive compounds'.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                16 January 2019
                January 2019
                : 20
                : 2
                : 351
                Affiliations
                [1 ]Dipartimento di Medicina e Chirurgia, Unità di Neuroscienze, Università di Parma, via Volturno 39/F, 43125 Parma, Italy; francesco.poti@ 123456unipr.it
                [2 ]Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze, Unità di Endocrinologia, Università degli Studi di Modena e Reggio Emilia, via del Pozzo 71, 41124 Modena, Italy; daniele.santi@ 123456unimore.it
                [3 ]Dipartimento di Medicine Specialistiche-Unità di Endocrinologia, Azienda Ospedaliero-Universitaria di Modena, Ospedale Civile di Baggiovara, via Giardini 1355, 41126 Modena, Italy; giorgia.spaggiari87@ 123456gmail.com
                [4 ]Dipartimento di Scienze degli Alimenti e del Farmaco, Università di Parma, Parco Area delle Scienze 27/A, 43124 Parma, Italy; francesca.zimetti@ 123456unipr.it
                Author notes
                [* ]Correspondence: ilaria.zanotti@ 123456unipr.it ; Tel.: +39-0521-905040
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-1708-0719
                https://orcid.org/0000-0002-6665-263X
                https://orcid.org/0000-0003-2701-6021
                Article
                ijms-20-00351
                10.3390/ijms20020351
                6359281
                30654461
                fca35bc2-6c94-43fb-b87f-50116fc4a01b
                © 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
                : 07 December 2018
                : 11 January 2019
                Categories
                Review

                Molecular biology
                polyphenols,prevention,cardiovascular disease,neurodegenerative disease,cognitive decline,meta-analysis,blood pressure,flow mediated dilation,low density lipoproteins,memory

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