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Ferulic Acid Metabolites Attenuate LPS-Induced Inflammatory Response in Enterocyte-like Cells

Ferulic acid (FA) is a polyphenol pertaining to the class of hydroxycinnamic acids present in numerous foods of a plant origin. Its dietary consumption leads to the formation of several phase I and II metabolites in vivo, which represent the largest amount of ferulates in the circulation and in the...

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Autores principales: Serreli, Gabriele, Naitza, Micaela Rita, Zodio, Sonia, Leoni, Vera Piera, Spada, Martina, Melis, Maria Paola, Boronat, Anna, Deiana, Monica
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8471535/
https://www.ncbi.nlm.nih.gov/pubmed/34579029
http://dx.doi.org/10.3390/nu13093152
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author Serreli, Gabriele
Naitza, Micaela Rita
Zodio, Sonia
Leoni, Vera Piera
Spada, Martina
Melis, Maria Paola
Boronat, Anna
Deiana, Monica
author_facet Serreli, Gabriele
Naitza, Micaela Rita
Zodio, Sonia
Leoni, Vera Piera
Spada, Martina
Melis, Maria Paola
Boronat, Anna
Deiana, Monica
author_sort Serreli, Gabriele
collection PubMed
description Ferulic acid (FA) is a polyphenol pertaining to the class of hydroxycinnamic acids present in numerous foods of a plant origin. Its dietary consumption leads to the formation of several phase I and II metabolites in vivo, which represent the largest amount of ferulates in the circulation and in the intestine in comparison with FA itself. In this work, we evaluated their efficacy against the proinflammatory effects induced by lipopolysaccharide (LPS) in intestinal Caco-2 cell monolayers, as well as the mechanisms underlying their protective action. LPS-induced overexpression of proinflammatory enzymes such as inducible nitric oxide synthase (iNOS) and the consequent hyperproduction of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) were limited by physiological relevant concentrations (1 µM) of FA, its derivatives isoferulic acid (IFA) and dihydroferulic acid (DHFA), and their glucuronidated and sulfated metabolites, which acted upstream by limiting the activation of MAPK p38 and ERK and of Akt kinase, thus decreasing the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB) translocation into the nucleus. Furthermore, the compounds were found to promote the expression of Nrf2, which may have contributed to the downregulation of NF-ĸB activity. The overall data show that phase I/II metabolites retain the efficacy of their dietary free form in contrasting inflammatory response.
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spelling pubmed-84715352021-09-28 Ferulic Acid Metabolites Attenuate LPS-Induced Inflammatory Response in Enterocyte-like Cells Serreli, Gabriele Naitza, Micaela Rita Zodio, Sonia Leoni, Vera Piera Spada, Martina Melis, Maria Paola Boronat, Anna Deiana, Monica Nutrients Article Ferulic acid (FA) is a polyphenol pertaining to the class of hydroxycinnamic acids present in numerous foods of a plant origin. Its dietary consumption leads to the formation of several phase I and II metabolites in vivo, which represent the largest amount of ferulates in the circulation and in the intestine in comparison with FA itself. In this work, we evaluated their efficacy against the proinflammatory effects induced by lipopolysaccharide (LPS) in intestinal Caco-2 cell monolayers, as well as the mechanisms underlying their protective action. LPS-induced overexpression of proinflammatory enzymes such as inducible nitric oxide synthase (iNOS) and the consequent hyperproduction of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) were limited by physiological relevant concentrations (1 µM) of FA, its derivatives isoferulic acid (IFA) and dihydroferulic acid (DHFA), and their glucuronidated and sulfated metabolites, which acted upstream by limiting the activation of MAPK p38 and ERK and of Akt kinase, thus decreasing the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB) translocation into the nucleus. Furthermore, the compounds were found to promote the expression of Nrf2, which may have contributed to the downregulation of NF-ĸB activity. The overall data show that phase I/II metabolites retain the efficacy of their dietary free form in contrasting inflammatory response. MDPI 2021-09-10 /pmc/articles/PMC8471535/ /pubmed/34579029 http://dx.doi.org/10.3390/nu13093152 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Serreli, Gabriele
Naitza, Micaela Rita
Zodio, Sonia
Leoni, Vera Piera
Spada, Martina
Melis, Maria Paola
Boronat, Anna
Deiana, Monica
Ferulic Acid Metabolites Attenuate LPS-Induced Inflammatory Response in Enterocyte-like Cells
title Ferulic Acid Metabolites Attenuate LPS-Induced Inflammatory Response in Enterocyte-like Cells
title_full Ferulic Acid Metabolites Attenuate LPS-Induced Inflammatory Response in Enterocyte-like Cells
title_fullStr Ferulic Acid Metabolites Attenuate LPS-Induced Inflammatory Response in Enterocyte-like Cells
title_full_unstemmed Ferulic Acid Metabolites Attenuate LPS-Induced Inflammatory Response in Enterocyte-like Cells
title_short Ferulic Acid Metabolites Attenuate LPS-Induced Inflammatory Response in Enterocyte-like Cells
title_sort ferulic acid metabolites attenuate lps-induced inflammatory response in enterocyte-like cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8471535/
https://www.ncbi.nlm.nih.gov/pubmed/34579029
http://dx.doi.org/10.3390/nu13093152
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