Publikationsdatenbank

Comparative studies of urolithins and their phase II metabolites on macrophage and neutrophil functions (2021)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Bobowska, Aneta

Grancia, Sebastian

Filipek, Agnieszka

Melzig, Matthias F.

Moeslinger, Thomas

Zentek, Jürgen (WE 4)

Kruk, Aleksandra

Piwowarski, Jakub P. (WE 4)

Quelle

European journal of nutrition

Bandzählung: 60

Heftzählung: 4

Seiten: 1957 – 1972

ISSN: 1436-6215

Sprache

Englisch

Verweise

URL (Volltext): https://link.springer.com/article/10.1007/s00394-020-02386-y

DOI: 10.1007/s00394-020-02386-y

Pubmed: 32960290

Kontakt

Institut für Tierernährung

Königin-Luise-Str. 49
14195 Berlin
+49 30 838 52256
tierernaehrung@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Purpose
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.

Methods
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.

Results
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.

Conclusion
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.