Purpose Ellagitannins are high molecular weight polyphenols present in high quantities in various food products. They are metabolized by human and animal gut microbiota to postbiotic metabolites-urolithins, bioavailable molecules of a low molecular weight. Following absorption in the gut, urolithins rapidly undergo phase II metabolism. Thus, to fully evaluate the mechanisms of their biological activity, the in vitro studies should be conducted for their phase II conjugates, mainly glucuronides. The aim of the study was to comparatively determine the influence of urolithin A, iso-urolithin A, and urolithin B together with their respective glucuronides on processes associated with the inflammatory response. Methods The urolithins obtained by chemical synthesis or isolation from microbiota cultures were tested with their respective glucuronides isolated from human urine towards modulation of inflammatory response in THP-1-derived macrophages, RAW 264.7 macrophages, PBMCs-derived macrophages, and primary neutrophils. Results Urolithin A was confirmed to be the most active metabolite in terms of LPS-induced inflammatory response inhibition (TNF-α attenuation, IL-10 induction). The observed strong induction of ERK1/2 phosphorylation has been postulated as the mechanism of its action. None of the tested glucuronide conjugates was active in terms of pro-inflammatory TNF-α inhibition and anti-inflammatory IL-10 and TGF-β1 induction. Conclusion Comparative studies of the most abundant urolithins and their phase II conjugates conducted on human and murine immune cells unambiguously confirmed urolithin A to be the most active metabolite in terms of inhibition of the inflammatory response. Phase II metabolism was shown to result in the loss of urolithins’ pharmacological properties.

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In this work, molybdenum disulfide nanosheets were electrophoretically co-deposited with PEEK 708 microparticles to fabricate composite coatings on Ti-6Al-4V titanium alloy substrates. Different dispersion media, pure ethanol and ethanol with the addition of cationic chitosan polyelectrolyte have been studied. The co-deposition mechanisms were indicated based on zeta potential measurements and investigation of the interaction between particles in the suspension using electron microscopy. The composite coatings deposited from the suspension containing a low amount of MoS 2 stabilized by chitosan were homogeneous. The polymer morphology changed as a result of heat-treatment from granular in the as-deposited coating into a dense, continuous matrix in the heat treated coating. The separate MoS 2 nanosheets and their packages were relatively homogeneously distributed and formed arrays that were mainly parallel to the coating surface. The coatings exhibited an amorphous structure regardless of the applied cooling rate after heating. The amorphization of the coating, slowly cooled after heating above the melting point, is due to the partial diffusion of sulfur from MoS 2 to PEEK 708 and its sulfonation. The obtained results provide new knowledge regarding the co-deposition mechanisms of MoS 2 and PEEK in the presence of chitosan and polymer sulfonating at elevated temperatures.

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