Effect of Hops Derived Prenylated Phenols on TNF-α Induced Barrier Dysfunction in Intestinal Epithelial Cells

For the prenylated hops phenols 6- and 8-prenylnaringenin (1 and 2), xanthohumol (3), and isoxanthohuniol (4), a variety of biological activities has been described. In the current study, a transwell based in vitro model using the human intestinal epithelialcell line Caco-2 was developed to assess potential- beneficial-effects of compounds 1-4. on TNF-alpha-induced impairment of tight junction (TJ) permeability. Trans epithelial electrical resistance (TEER) was measured using the, latest cellZScope online monitoring device. TNF-alpha treatment (26 mu g/mL) induced a significant decrease in TEER values (204.71 +/- 4.57 at 72 h) compared to that in control values (245.94 +/- 1.68 at 72 h). To determine preventive effects on TNF-alpha-induced impairment of TJ permeability; 1-4 were added to the apical compartment of CacO-2 monolayers 1 h before TNF-alpha treatment; afterward, TNF-alpha was added to the f-basolateral compartment to induce TJ dysfunction and incubated for a further 72-h. Using this setting, only 1 and 2 prevented epithelial disruption induced by TNF-alpha. To evaluate restorative effects of 1-4, TNF-alpha was added to the basolateral compartment, of Caco,2 celLmonolayers. After 48 h of incubation, 1,-4 were added to the apical side, and TEER values were monitored online for a further 72 h. Under these experimental conditions, only 2 restored TNF-alpha induced barrier dysfunction.