Flavonoid-mediated immunomodulation of human macrophages involves key metabolites and metabolic pathways
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10773/34738 |
Resumo: | The ability of flavonoids to attenuate macrophage pro-inflammatory activity and to promote macrophage-mediated resolution of inflammation is still poorly understood at the biochemical level. In this study, we have employed NMR metabolomics to assess how therapeutically promising flavonoids (quercetin, naringenin and naringin) affect the metabolism of human macrophages, with a view to better understand their biological targets and activity. In vitro-cultured human macrophages were polarized to the pro-inflammatory M1 phenotype, through incubation with LPS + IFN-γ, and subsequently treated with each flavonoid. The metabolic signatures of pro-inflammatory polarization and of flavonoid incubations were then characterized and compared. The results showed that all flavonoids modulated the cells endometabolome with the strongest impact being observed for quercetin. Many of the flavonoid-induced metabolic variations were in the opposite sense to those elicited by pro-inflammatory stimulation. In particular, the metabolic processes proposed to reflect flavonoid-mediated immunomodulation of macrophages included the downregulation of glycolytic activity, observed for all flavonoids, anti-inflammatory reprogramming of the TCA cycle (mainly quercetin), increased antioxidant protection (quercetin), osmoregulation (naringin), and membrane modification (naringenin). This work revealed key metabolites and metabolic pathways involved in macrophage responses to quercetin, naringenin and naringin, providing novel insights into their immunomodulatory activity. |
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Flavonoid-mediated immunomodulation of human macrophages involves key metabolites and metabolic pathwaysThe ability of flavonoids to attenuate macrophage pro-inflammatory activity and to promote macrophage-mediated resolution of inflammation is still poorly understood at the biochemical level. In this study, we have employed NMR metabolomics to assess how therapeutically promising flavonoids (quercetin, naringenin and naringin) affect the metabolism of human macrophages, with a view to better understand their biological targets and activity. In vitro-cultured human macrophages were polarized to the pro-inflammatory M1 phenotype, through incubation with LPS + IFN-γ, and subsequently treated with each flavonoid. The metabolic signatures of pro-inflammatory polarization and of flavonoid incubations were then characterized and compared. The results showed that all flavonoids modulated the cells endometabolome with the strongest impact being observed for quercetin. Many of the flavonoid-induced metabolic variations were in the opposite sense to those elicited by pro-inflammatory stimulation. In particular, the metabolic processes proposed to reflect flavonoid-mediated immunomodulation of macrophages included the downregulation of glycolytic activity, observed for all flavonoids, anti-inflammatory reprogramming of the TCA cycle (mainly quercetin), increased antioxidant protection (quercetin), osmoregulation (naringin), and membrane modification (naringenin). This work revealed key metabolites and metabolic pathways involved in macrophage responses to quercetin, naringenin and naringin, providing novel insights into their immunomodulatory activity.Springer Nature2022-09-22T10:28:31Z2019-12-01T00:00:00Z2019-12-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10773/34738eng2045-232210.1038/s41598-019-51113-zMendes, Luís F.Gaspar, Vítor M.Conde, Tiago A.Mano, João F.Duarte, Iola F.info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-02-22T12:07:18Zoai:ria.ua.pt:10773/34738Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:06:05.101798Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Flavonoid-mediated immunomodulation of human macrophages involves key metabolites and metabolic pathways |
title |
Flavonoid-mediated immunomodulation of human macrophages involves key metabolites and metabolic pathways |
spellingShingle |
Flavonoid-mediated immunomodulation of human macrophages involves key metabolites and metabolic pathways Mendes, Luís F. |
title_short |
Flavonoid-mediated immunomodulation of human macrophages involves key metabolites and metabolic pathways |
title_full |
Flavonoid-mediated immunomodulation of human macrophages involves key metabolites and metabolic pathways |
title_fullStr |
Flavonoid-mediated immunomodulation of human macrophages involves key metabolites and metabolic pathways |
title_full_unstemmed |
Flavonoid-mediated immunomodulation of human macrophages involves key metabolites and metabolic pathways |
title_sort |
Flavonoid-mediated immunomodulation of human macrophages involves key metabolites and metabolic pathways |
author |
Mendes, Luís F. |
author_facet |
Mendes, Luís F. Gaspar, Vítor M. Conde, Tiago A. Mano, João F. Duarte, Iola F. |
author_role |
author |
author2 |
Gaspar, Vítor M. Conde, Tiago A. Mano, João F. Duarte, Iola F. |
author2_role |
author author author author |
dc.contributor.author.fl_str_mv |
Mendes, Luís F. Gaspar, Vítor M. Conde, Tiago A. Mano, João F. Duarte, Iola F. |
description |
The ability of flavonoids to attenuate macrophage pro-inflammatory activity and to promote macrophage-mediated resolution of inflammation is still poorly understood at the biochemical level. In this study, we have employed NMR metabolomics to assess how therapeutically promising flavonoids (quercetin, naringenin and naringin) affect the metabolism of human macrophages, with a view to better understand their biological targets and activity. In vitro-cultured human macrophages were polarized to the pro-inflammatory M1 phenotype, through incubation with LPS + IFN-γ, and subsequently treated with each flavonoid. The metabolic signatures of pro-inflammatory polarization and of flavonoid incubations were then characterized and compared. The results showed that all flavonoids modulated the cells endometabolome with the strongest impact being observed for quercetin. Many of the flavonoid-induced metabolic variations were in the opposite sense to those elicited by pro-inflammatory stimulation. In particular, the metabolic processes proposed to reflect flavonoid-mediated immunomodulation of macrophages included the downregulation of glycolytic activity, observed for all flavonoids, anti-inflammatory reprogramming of the TCA cycle (mainly quercetin), increased antioxidant protection (quercetin), osmoregulation (naringin), and membrane modification (naringenin). This work revealed key metabolites and metabolic pathways involved in macrophage responses to quercetin, naringenin and naringin, providing novel insights into their immunomodulatory activity. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-12-01T00:00:00Z 2019-12-01 2022-09-22T10:28:31Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10773/34738 |
url |
http://hdl.handle.net/10773/34738 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2045-2322 10.1038/s41598-019-51113-z |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Springer Nature |
publisher.none.fl_str_mv |
Springer Nature |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799137715824885760 |