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      Wine Flavonoids in Health and Disease Prevention

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          Abstract

          Wine, and particularly red wine, is a beverage with a great chemical complexity that is in continuous evolution. Chemically, wine is a hydroalcoholic solution (~78% water) that comprises a wide variety of chemical components, including aldehydes, esters, ketones, lipids, minerals, organic acids, phenolics, soluble proteins, sugars and vitamins. Flavonoids constitute a major group of polyphenolic compounds which are directly associated with the organoleptic and health-promoting properties of red wine. However, due to the insufficient epidemiological and in vivo evidences on this subject, the presence of a high number of variables such as human age, metabolism, the presence of alcohol, the complex wine chemistry, and the wide array of in vivo biological effects of these compounds suggest that only cautious conclusions may be drawn from studies focusing on the direct effect of wine and any specific health issue. Nevertheless, there are several reports on the health protective properties of wine phenolics for several diseases such as cardiovascular diseases, some cancers, obesity, neurodegenerative diseases, diabetes, allergies and osteoporosis. The different interactions that wine flavonoids may have with key biological targets are crucial for some of these health-promoting effects. The interaction between some wine flavonoids and some specific enzymes are one example. The way wine flavonoids may be absorbed and metabolized could interfere with their bioavailability and therefore in their health-promoting effect. Hence, some reports have focused on flavonoids absorption, metabolism, microbiota effect and overall on flavonoids bioavailability. This review summarizes some of these major issues which are directly related to the potential health-promoting effects of wine flavonoids. Reports related to flavonoids and health highlight some relevant scientific information. However, there is still a gap between the knowledge of wine flavonoids bioavailability and their health-promoting effects. More in vivo results as well as studies focused on flavonoid metabolites are still required. Moreover, it is also necessary to better understand how biological interactions (with microbiota and cells, enzymes or general biological systems) could interfere with flavonoid bioavailability.

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          Flavonoids: antioxidants or signalling molecules?

          Many studies are accumulating that report the neuroprotective, cardioprotective, and chemopreventive actions of dietary flavonoids. While there has been a major focus on the antioxidant properties, there is an emerging view that flavonoids, and their in vivo metabolites, do not act as conventional hydrogen-donating antioxidants but may exert modulatory actions in cells through actions at protein kinase and lipid kinase signalling pathways. Flavonoids, and more recently their metabolites, have been reported to act at phosphoinositide 3-kinase (PI 3-kinase), Akt/protein kinase B (Akt/PKB), tyrosine kinases, protein kinase C (PKC), and mitogen activated protein kinase (MAP kinase) signalling cascades. Inhibitory or stimulatory actions at these pathways are likely to affect cellular function profoundly by altering the phosphorylation state of target molecules and by modulating gene expression. A clear understanding of the mechanisms of action of flavonoids, either as antioxidants or modulators of cell signalling, and the influence of their metabolism on these properties are key to the evaluation of these potent biomolecules as anticancer agents, cardioprotectants, and inhibitors of neurodegeneration
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            Insights into the metabolism and microbial biotransformation of dietary flavan-3-ols and the bioactivity of their metabolites.

            Flavan-3-ols, occurring in monomeric, as well as in oligomeric and polymeric forms (also known as condensed tannins or proanthocyanidins), are among the most abundant and bioactive dietary polyphenols, but their in vivo health effects in humans may be limited because of their recognition as xenobiotics. Bioavailability of flavan-3-ols is largely influenced by their degree of polymerization; while monomers are readily absorbed in the small intestine, oligomers and polymers need to be biotransformed by the colonic microbiota before absorption. Therefore, phenolic metabolites, rather than the original high molecular weight compounds found in foods, may be responsible for the health effects derived from flavan-3-ol consumption. Flavan-3-ol phenolic metabolites differ in structure, amount and excretion site. Phase II or tissular metabolites derived from the small intestine and hepatic metabolism are presented as conjugated derivatives (glucuronic acid or sulfate esters, methyl ether, or their combined forms) of monomeric flavan-3-ols and are preferentially eliminated in the bile, whereas microbial metabolites are rather simple conjugated lactones and phenolic acids that are largely excreted in urine. Although the colon is seen as an important organ for the metabolism of flavan-3-ols, the microbial catabolic pathways of these compounds are still under consideration, partly due to the lack of identification of bacteria with such capacity. Studies performed with synthesized or isolated phase II conjugated metabolites have revealed that they could have an effect beyond their antioxidant properties, by interacting with signalling pathways implicated in important processes involved in the development of diseases, among other bioactivities. However, the biological properties of microbe-derived metabolites in their actual conjugated forms remain largely unknown. Currently, there is an increasing interest in their effects on intestinal infections, inflammatory intestinal diseases and overall gut health. The present review will give an insight into the metabolism and microbial biotransformation of flavan-3-ols, including tentative catabolic pathways and aspects related to the identification of bacteria with the ability to catabolize these kinds of polyphenols. Also, the in vitro bioactivities of phase II and microbial phenolic metabolites will be covered in detail.
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              Alcohol consumption as a risk factor for dementia and cognitive decline: meta-analysis of prospective studies.

              The relationships between alcohol consumption and dementia and cognitive decline were investigated in a systematic review including meta-analyses of 15 prospective studies. Follow-ups ranged from 2 to 8 years. Meta-analyses were conducted on samples including 14,646 participants evaluated for Alzheimer disease (AD), 10,225 participants evaluated for vascular dementia (VaD), and 11,875 followed for any type of dementia (Any dementia). The pooled relative risks (RRs) of AD, VaD, and Any dementia for light to moderate drinkers compared with nondrinkers were 0.72 (95% CI = 0.61-0.86), 0.75 (95% CI = 0.57-0.98), and 0.74 (95% CI = 0.61-0.91), respectively. When the more generally classified "drinkers," were compared with "nondrinkers," they had a reduced risk of AD (RR = 0.66, 95% CI = 0.47-0.94) and Any dementia (RR = 0.53, 95% CI = 0.53-0.82) but not cognitive decline. There were not enough data to examine VaD risk among "drinkers." Those classified as heavy drinkers did not have an increased risk of Any dementia compared with nondrinkers, but this may reflect sampling bias. Our results suggest that alcohol drinkers in late life have reduced risk of dementia. It is unclear whether this reflects selection effects in cohort studies commencing in late life, a protective effect of alcohol consumption throughout adulthood, or a specific benefit of alcohol in late life.
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                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Journal
                Molecules
                Molecules
                molecules
                Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry
                MDPI
                1420-3049
                14 February 2017
                February 2017
                : 22
                : 2
                : 292
                Affiliations
                LAQV/REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade do Porto, Rua do Campo Alegre 687, 4169-007 Porto, Portugal; iva.fernandes@ 123456fc.up.pt (I.F.); rosi.perez.gregorio@ 123456gmail.com (R.P.-G.); susana.soares@ 123456fc.up.pt (S.S.); vfreitas@ 123456fc.up.pt (V.d.F.)
                Author notes
                [* ]Correspondence: nbmateus@ 123456fc.up.pt ; Tel.: +351-220-402-562; Fax: +351-220-402-659
                Article
                molecules-22-00292
                10.3390/molecules22020292
                6155685
                28216567
                f91e81cc-ad3c-44db-ba6b-67fae885ab40
                © 2017 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 November 2016
                : 10 February 2017
                Categories
                Review

                wine polyphenols,polyphenol-protein interactions,bioavailability of wine polyphenols,health,biological effects

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