J Ethnopharmacol. 2014 Aug 8;155(1):801-9. doi: 10.1016/j.jep.2014.06.032. Epub 2014 Jun 23.

Role of human gut microbiota metabolism in the anti-inflammatory effect of traditionally used ellagitannin-rich plant materials.

Piwowarski JP1, Granica S2, Zwierzyńska M2, Stefańska J3, Schopohl P4, Melzig MF4, Kiss AK2.

• 1Department 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.
• 2Department of Pharmacognosy and Molecular Basis of Phytotherapy, Medical University of Warsaw, Faculty of Pharmacy, Banacha 1, 02-097 Warsaw, Poland.
• 3Department of Pharmaceutical Microbiology, Medical University of Warsaw, Oczki 3, 02-007 Warsaw, Poland.
• 4Institute of Pharmacy, Freie Universitaet Berlin, Königin-Luise-Straße 2 and 4, 14195 Berlin, Germany.

ETHNOPHARMACOLOGICAL RELEVANCE:

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.

MATERIALS AND 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.

Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

PMID:

24969824