Comparative studies of urolithins and their phase II metabolites on macrophage and neutrophil functions.
Ellagitannins
Inflammation
Phase II metabolism
Postbiotics
Urolithins
Journal
European journal of nutrition
ISSN: 1436-6215
Titre abrégé: Eur J Nutr
Pays: Germany
ID NLM: 100888704
Informations de publication
Date de publication:
Jun 2021
Jun 2021
Historique:
received:
07
04
2020
accepted:
10
09
2020
pubmed:
23
9
2020
medline:
24
6
2021
entrez:
22
9
2020
Statut:
ppublish
Résumé
Ellagitannins are high molecular weight polyphenols present in high quantities in various food products. They are metabolized by human and animal gut microbiota to postbiotic metabolites-urolithins, bioavailable molecules of a low molecular weight. Following absorption in the gut, urolithins rapidly undergo phase II metabolism. Thus, to fully evaluate the mechanisms of their biological activity, the in vitro studies should be conducted for their phase II conjugates, mainly glucuronides. The aim of the study was to comparatively determine the influence of urolithin A, iso-urolithin A, and urolithin B together with their respective glucuronides on processes associated with the inflammatory response. The urolithins obtained by chemical synthesis or isolation from microbiota cultures were tested with their respective glucuronides isolated from human urine towards modulation of inflammatory response in THP-1-derived macrophages, RAW 264.7 macrophages, PBMCs-derived macrophages, and primary neutrophils. Urolithin A was confirmed to be the most active metabolite in terms of LPS-induced inflammatory response inhibition (TNF-α attenuation, IL-10 induction). The observed strong induction of ERK1/2 phosphorylation has been postulated as the mechanism of its action. None of the tested glucuronide conjugates was active in terms of pro-inflammatory TNF-α inhibition and anti-inflammatory IL-10 and TGF-β1 induction. Comparative studies of the most abundant urolithins and their phase II conjugates conducted on human and murine immune cells unambiguously confirmed urolithin A to be the most active metabolite in terms of inhibition of the inflammatory response. Phase II metabolism was shown to result in the loss of urolithins' pharmacological properties.
Identifiants
pubmed: 32960290
doi: 10.1007/s00394-020-02386-y
pii: 10.1007/s00394-020-02386-y
pmc: PMC8137622
doi:
Substances chimiques
Anti-Inflammatory Agents
0
Coumarins
0
Hydrolyzable Tannins
0
Types de publication
Clinical Trial, Phase II
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1957-1972Subventions
Organisme : Polish Ministry of Science and Higher Education
ID : Iuventus Plus [IP2015 062274]
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