title: Role of human gut microbiota metabolism in the anti-inflammatory effect of traditionally used ellagitannin-rich plant materials.
abstract: BACKGROUND
  Ellagitannin-rich plant materials are widely used in traditional medicine as effective, internally used anti-inflammatory agents. Due to the not well-established bioavailability of ellagitannins, the mechanisms of observed therapeutic effects following oral administration still remain unclear. The aim of the study was to evaluate if selected ellagitannin-rich plant materials could be the source of bioavailable gut microbiota metabolites, i.e. urolithins, together with determination of the anti-inflammatory activity of the metabolites produced on the THP-1 cell line derived macrophages model.
  
  
  METHODS
  The formation of urolithins was determined by ex vivo incubation of human fecal samples with aqueous extracts from selected plant materials. The anti-inflammatory activity study of metabolites was determined on PMA differentiated, IFN-γ and LPS stimulated, human THP-1 cell line-derived macrophages.
  
  
  RESULTS
  The formation of urolithin A, B and C by human gut microbiota was established for aqueous extracts from Filipendula ulmaria (L.) Maxim. herb (Ph. Eur.), Geranium pratense L. herb, Geranium robertianum L. herb, Geum urbanum L. root and rhizome, Lythrum salicaria L. herb (Ph. Eur.), Potentilla anserina L. herb, Potentilla erecta (L.) Raeusch rhizome (Ph. Eur.), Quercus robur L. bark (Ph. Eur.), Rubus idaeus L. leaf, Rubus fruticosus L. and pure ellagitannin vescalagin. Significant inhibition of TNF-α production was determined for all urolithins, while for the most potent urolithin A inhibition was observed at nanomolar concentrations (at 0.625 μM 29.2±6.4% of inhibition). Urolithin C was the only compound inhibiting IL-6 production (at 0.625 μM 13.9±2.2% of inhibition).
  
  
  CONCLUSIONS
  The data obtained clearly indicate that in the case of peroral use of the examined ellagitannin-rich plant materials the bioactivity of gut microbiota metabolites, i.e. urolithins, has to be taken under consideration.
authors: Department of Pharmacognosy and Molecular Basis of Phytotherapy, Medical University of Warsaw, Faculty of Pharmacy, Banacha 1, 02-097 Warsaw, Poland. Electronic address: jakub.piwowarski@wum.edu.pl.
authors: Jakub P
authors: JP
authors: Piwowarski
authors: Department of Pharmacognosy and Molecular Basis of Phytotherapy, Medical University of Warsaw, Faculty of Pharmacy, Banacha 1, 02-097 Warsaw, Poland.
authors: Sebastian
authors: S
authors: Granica
authors: Department of Pharmacognosy and Molecular Basis of Phytotherapy, Medical University of Warsaw, Faculty of Pharmacy, Banacha 1, 02-097 Warsaw, Poland.
authors: Marta
authors: M
authors: Zwierzyńska
authors: Department of Pharmaceutical Microbiology, Medical University of Warsaw, Oczki 3, 02-007 Warsaw, Poland.
authors: Joanna
authors: J
authors: Stefańska
authors: Institute of Pharmacy, Freie Universitaet Berlin, Königin-Luise-Straße 2 and 4, 14195 Berlin, Germany.
authors: Patrick
authors: P
authors: Schopohl
authors: Institute of Pharmacy, Freie Universitaet Berlin, Königin-Luise-Straße 2 and 4, 14195 Berlin, Germany.
authors: Matthias F
authors: MF
authors: Melzig
authors: Department of Pharmacognosy and Molecular Basis of Phytotherapy, Medical University of Warsaw, Faculty of Pharmacy, Banacha 1, 02-097 Warsaw, Poland.
authors: Anna K
authors: AK
authors: Kiss
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D003374:Coumarins / Q000378:metabolism / Q000494:pharmacology; D005243:Feces / Q000382:microbiology; D041981:Gastrointestinal Tract / Q000382:microbiology; D006801:Humans; D047348:Hydrolyzable Tannins / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008519:Medicine, Traditional; D064307:Microbiota / Q000502:physiology; D008875:Middle Aged; D010936:Plant Extracts / Q000378:metabolism / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha
chemical_list: D000893:Anti-Inflammatory Agents; D003374:Coumarins; D047348:Hydrolyzable Tannins; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; C013515:ellagitannin; C000595064:urolithin B; C588364:urolithin C; C026423:3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one
keywords: Ellagitannins; Gut microbiota; Inflammation; SB-203580 (PubChem CID: 176155); Urolithin A (PubChem CID: 5488186); Urolithin B (PubChem CID: 5380406); Urolithin C (Reaxys registry number: 5050777); Urolithins