Conclusions
The results show that physiologically relevant colonic Uro target eicosanoid biosynthetic pathways. The effect on HKs and LTB4 formation is unprecedented and expands the knowledge on anti-inflammatory mechanisms of Uro against IBDs.
Results
Leukocytes, obtained from six healthy donors, are stimulated with lipopolysaccharide and calcium ionophore A23187. Uro, at concentrations found in the human colon (1-15 µm), decrease eicosanoid biosynthesis and COX-2 levels in the activated leukocytes. In contrast, EA and conjugated Uro (glucuronides and sulfates) are inactive. Uro-A and isourolithin-A reduce the formation of the 5-LOX/COX-2 products HKE2 and HKD2 through the COX-2 pathway (down-regulation of COX-2 and PGE2), whereas Uro-C reduces 5-HETE and LTB4 via inhibition of 5-LOX. Conclusions: The results show that physiologically relevant colonic Uro target eicosanoid biosynthetic pathways. The effect on HKs and LTB4 formation is unprecedented and expands the knowledge on anti-inflammatory mechanisms of Uro against IBDs.