title: Urolithins, gut microbiota-derived metabolites of ellagitannins, inhibit LPS-induced inflammation in RAW 264.7 murine macrophages.
abstract: METHODS
  Ellagitannin-rich food products and medicinal plant materials were shown to have beneficial effects toward intestinal inflammation. Due to the questionable bioavailability of ellagitannins their gut microbiota metabolites-urolithins have come to be regarded as potential factors responsible for biological activities observed in vivo. The aim of the study was to determine the influence of the three most abundant bioavailable ellagitannin gut microbiota metabolites-urolithins A, B, and C on inflammatory responses in RAW 264.7 murine macrophages, which are involved in the pathogenesis of intestine inflammation.
  
  
  RESULTS
  Urolithins A, B, and C decreased NO production via inhibition of the iNOS protein and mRNA expression. They decreased the expression of IL-1β, TNF-α, and IL-6 mRNA in LPS challenged RAW 264.7 murine macrophages. A clear inhibition of NF-κB p65 nuclear translocation and p50 DNA-binding activity was associated with the observed anti-inflammatory activities of urolithins. Among the tested compounds urolithin A had the strongest anti-inflammatory activity.
  
  
  CONCLUSIONS
  The anti-inflammatory effects of urolithins at concentrations that are physiologically relevant for gut tissues (≥40 μM), as revealed in this study, support the data from in vivo studies showing the beneficial effects of ellagitannin-rich products toward intestinal inflammation.
authors.affiliation: Department of Pharmacognosy and Molecular Basis of Phytotherapy, Faculty of Pharmacy, Medical University of Warsaw, Warsaw, Poland.|Institute of Physiology, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: Jakub P
authors.initials: JP
authors.lastname: Piwowarski
authors.affiliation: Department of Pharmacognosy and Molecular Basis of Phytotherapy, Faculty of Pharmacy, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Kiss
authors.affiliation: Department of Pharmacognosy and Molecular Basis of Phytotherapy, Faculty of Pharmacy, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Granica
authors.affiliation: Institute of Physiology, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Moeslinger
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D003374:Coumarins / Q000494:pharmacology*; D000069196:Gastrointestinal Microbiome; D047348:Hydrolyzable Tannins / Q000378:metabolism* / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D000067996:RAW 264.7 Cells
chemical_list: D000893:Anti-Inflammatory Agents; D003374:Coumarins; D047348:Hydrolyzable Tannins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C013515:ellagitannin; C000595064:urolithin B; C588364:urolithin C; C026423:3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II
keywords: Ellagitannins; Inflammation; Inflammatory bowel disease; Macrophages; Urolithins