Influence of urolithins on inflammatory response of RAW 264.7 murine macrophages

Ellagitannin-rich medicinal plants and food products are known to express beneficial effects towards chronic intestinal inflammation. Due to not fully established bioavailability of ellagitannins currently their gut microbiota metabolites-urolithins are indicated as the potential factors being responsible for observed in vivo activities.

The aim of the study was to determine the influence of the three most abundant bioavailable gut microbiota metabolites-urolithins A, B and C on the LPS-induced inflammatory response of RAW 264.7 murine macrophages taking part in pathogenesis of the intestine inflammation.

Urolithins A, B and C decreased LPS-induced NO production. The strongest impact was observed in the case of urolithin A, which dose dependently inhibited NO production at the concentration range 2.5 – 40.0 µM with IC₅₀= 9.8 ± 2.1 µM. The determined effects were shown to depend on the inhibition of iNOS protein and mRNA expression. Moreover all tested urolithins at the concentration of 40 µM inhibited IL-1β, TNF-α and IL-6 mRNA expression in LPS challenged RAW 264.7 macrophages. Inhibition of NF-κB p65 nuclear translocation contributed to the observed anti-inflammatory activity of urolithins.

The anti-inflammatory effects demonstrated for urolithins A, B and C at the concentration range (≥40 µM) potentially reachable in the gut tissues, support observed in in vivo studies beneficial effects of ellagitannin-rich products in intestine inflammation.

Acknowledgements: The author was financially supported by the National Science Centre Center scholarship ETIUDA decision number DEC-2013/08/T/NZ7/00011.