Effects of hops derived prenylflavonoids on TNF-α induced barrier dysfunction in intestinal epithelial cells
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The human intestine allows the absorption of nutrients while also functioning as a barrier preventing pathogens from entering the mucosal tissues. Increased intestinal permeability is associated with autoimmune, inflammatory, and atopic diseases . Tight junctions (TJ) are specialized junctional complexes forming a seal between adjacent epithelial cells. Hops is a source of prenylflavonoids, including 6- and 8-prenylnaringenin (6-PN, 8-PN), xanthohumol (XN) and isoxanthohumol (IX) for which a variety of biological activities have been described. The aims of this study were to a) establish a cell culture model for barrier dysfunction using TNF-α to induce TJ damage in Caco-2 cells; b) to test if hops-derived prenylflavonoids can prevent TNF-α induced TJ damage; and c) to investigate if 6-PN; 8-PN, XN, and IX can restore TNF-α induced barrier dysfunction. After addition of TNF-α, the TEER value of Caco-2 cells demonstrated a significant decrease compared to the control group. From the tested compounds 6-PN and 8-PN prevented epithelial disruption induced by TNF-α, as assessed by measurement of TEER values. XN and IX also showed preventive effects, which occurred 60h after addition of TNF-α. Finally, it was of interest to determine possible treatment effects of XN, IX, 6-PN and 8-PN. Thus, TNF-α was added to Caco-2 cell monolayers for 24h before all test compounds were added. Under these experimental conditions only 8-PN significantly could antagonize TNF-α induced epithelial barrier dysfunction. Our results show for the first time that 8-PN from hops attenuated a cytokine-induced increase in intestinal epithelial TJ permeability.