16:00 - 18:00
Room: Poster Area - Poster Shed
Poster Presentation
Influence of urolithins and their glucuronides on pro-inflammatory response of THP-1 macrophages.
Jakub Piwowarski 1, 2, Aneta Bobowska 1, Sebastian Granica 1, Matthias F. Melzig 2
1 Department of Pharmacognosy and Molecular Basis of Phytotherapy, Faculty of Pharmacy, Medical University of Warsaw, Warsaw
2 Department of Pharmaceutical Biology, Institute of Pharmacy, Freie Universität Berlin, Berlin

Ellagitannins present in various medicinal plants are metabolized by human gut microbiota to bioavailable small molecule compounds- urolithins [1]. Urolithins after absorption in the gut rapidly undergo metabolism by II phase enzymes, what results in their presence in serum, tissues and urine mainly in forms conjugated with glucuronic acid. To fully evaluate biological activity of urolithins, the in vitro studies should be also conducted for their II phase metabolites, especially for dominating glucuronides.

The aim of the study was to evaluate influence of isourolithin A, urolithin A and urolithin B (iUA, UA, UB) as well as their respective glucuronides (GiUA, GUA, GUB) on TNF-α and IL-10 production after LPS stimulation of THP-1-derived macrophages.

THP-1 monocytes were differentiated into macrophages using PMA. UA at the concentration of 40 μM was capable of reducing LPS-induced TNF-α production by 59%, while GUA occurred to be inactive. The 24-hour incubation of THP-1 macrophages led to a significant increase in IL-10 production for all of the tested compounds, except for GiUA, whilst the strongest activity was observed for corresponding aglycone- iUA, which increased the production of this anti-inflammatory cytokine by 30%.

The above results confirm, that UA is the most active urolithin in terms of inhibiting the inflammation response after TLR4 receptor stimulation. iUA was for the first time indicated to trigger resolution of inflammation by increasing IL-10 production. II phase metabolism was shown to result in the loss of compounds’ pharmacological properties, however elevated β-glucuronidase activity at inflammation site is potent to cause their re-activation.

[1] Piwowarski JP, J Ethnopharmacol 2014; 155: 801-809

Acknowledgment: The project was financially supported by a Polish Ministry of Science and Higher Education research grant, Iuventus Plus [IP2015 062274].


Reference:
Poster Session-PO-78:
Session:
Poster Presentation-1
Presenter/s:
Jakub Piwowarski
Presentation type:
Poster presentation
Room:
Poster Area - Poster Shed
Date:
Monday, 27th August, 2018
Time:
16:00 - 18:00
Session times:
16:00 - 18:00