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

Abstract

For the prenylated hops phenols 6- and 8-prenylnaringenin (1 and 2), xanthohumol (3), and isoxanthohumol (4), a variety of biological activities has been described. In the current study, a transwell based in vitro model using the human intestinal epithelial cell line Caco-2 was developed to assess potential beneficial effects of compounds 1-4 on TNF-α-induced impairment of tight junction (TJ) permeability. Transepithelial electrical resistance (TEER) was measured using the latest cellZScope online monitoring device. TNF-α treatment (25 ng/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-α-induced impairment of TJ permeability, 1-4 were added to the apical compartment of Caco-2 monolayers 1 h before TNF-α treatment; afterward, TNF-α was added to the 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-α. To evaluate restorative effects of 1-4, TNF-α was added to the basolateral compartment of Caco-2 cell monolayers. 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-α induced barrier dysfunction.