Please use this identifier to cite or link to this item: https://hdl.handle.net/1889/2529
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dc.contributor.advisorDel Rio, Daniele-
dc.contributor.advisorOiry, Catherine-
dc.contributor.advisorCros, Gerard-
dc.contributor.authorDall'Asta, Margherita-
dc.date.accessioned2014-07-31T11:34:12Z-
dc.date.available2014-07-31T11:34:12Z-
dc.date.issued2014-
dc.identifier.urihttp://hdl.handle.net/1889/2529-
dc.description.abstractPolyphenolic compounds constitute one of the most numerous and ubiquitously distributed group of secondary metabolites in the plant kingdom. Nowadays, some thousands of structures of polyphenol have been reported, but many of them are found in only a limited number of species, and a large number of polyphenols could be still discovered. These data describe the powerful potential of this class of natural compounds in food science, nutrition research, drug discovery, and health promotion. The positive emerging effects on humans attributed to polyphenols have increased over the years thanks to research that has examined the activity of these bioactive molecules in different in vitro/ex vivo models and in vivo clinical trials. Recently, several epidemiological studies have highlighted and reinforced the polyphenol-beneficial effect link, although there are still no sufficient data to confirm their positive role in the prevention, in particular, of CVD, cancer, neurodegenerative disease, and diabetes. In this overview, the investigation of metabolism and bioavailability of polyphenols in humans is an essential step in understanding the biological activity of polyphenols in the organism, which depends on the capacity of the compounds to reach tissues, organs and cells, before exerting their positive actions. Certainly, the colon has been described, in human nutrition, as a powerful organ that is involved in the metabolism of food components. This bioreactor is a large ecosystem of microorganisms that is able to modify the 90-95% of polyphenols that arrive undigested in the large intestine and to release specific metabolites, derived from their degradation, into the bloodstream, playing a central role in their transformation and bioavailability During the last 20 years, several studies have been based on the evaluation of either the polyphenol-rich food extracts or native compounds on different experimental in vitro models. Moreover, the concentrations used in the experimental models were, in most cases, higher when compared to physiological data. This approach is misleading, as polyphenols appear within the human body as metabolites of hepatic/colonic origin at concentrations that rarely exceed the nanomoles per litre. On the basis of this evidence, this PhD thesis aims to investigate both the colonic metabolism of polyphenols and the effects of some selected metabolites on different in vitro and ex vivo models. The thesis is based on four experimental studies: 1. The identification of microbial metabolites derived from in vitro fecal fermentation of different polyphenolic food sources. Having targeted systematically the entire set of putative metabolites derived from the polyphenol fermentation of a range of common foods, the work brings new insights to better evaluate the bioavailability and putative preventive activity of polyphenols from specific food groups in humans. 2. The study of quercetin-3-O-glucuronide (Q3GA) on gene expression profile of M1 and M2a human macrophages. Q3GA was able to reduce in M1 the transcription of genes involved in inflammation, such as pro-inflammatory interleukins and enzymes involved in oxidative stress responses. Exposure of M2a to Q3GA elicited an improvement in anti-inflammatory features resulting from further down-regulation of pro-inflammatory genes. Thus, Q3GA is a potential anti-atherogenic metabolite, enhancing the anti-inflammatory properties of M2a macrophages and modulating immune response effects in the presence of pro-inflammatory stimuli. 3. The study of the effects of naringenin and its phase II metabolites on in vitro human macrophage gene expression. Phase II metabolites, as well as the aglyconic form of naringenin, were able to perturb macrophage gene expression in M1 and M2a in directions that are not always consistent with anti-inflammatory effects. Moreover, the effects of metabolites were not always consistent with each other and with those of their aglycone, underlining the paramount importance of testing physiological forms of phytochemicals within in vitro experimental models.it
dc.language.isoIngleseit
dc.publisherUniversità degli Studi di Parma. Dipartimento di Scienze degli Alimentiit
dc.publisherUniversité Montpellier 1. UFR des Sciences Pharmaceutiques et Biologiques pour la Santé (tesi in cotutela)it
dc.relation.ispartofseriesDottorato di ricerca in Scienze e Tecnologie Alimentari. Ecole Doctorale de Sciences Chimiques et Biologiques pour la santéit
dc.rights© Margherita Dall'Asta, 2014it
dc.subjectPolyphenolic compoundsit
dc.titleNew evidence on biological activity of polyphenol metabolitesit
dc.typeDoctoral thesisit
dc.subject.soggettarioChimica degli alimentiit
dc.subject.miurBIO/09it
Appears in Collections:Ingegneria industriale. Tesi di dottorato

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