title: 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.
authors.affiliation: Institute for Pharma Technology, School of Life Sciences, University of Applied Sciences Northwestern Switzerland , Gruendenstrasse 40, 4132 Muttenz, Switzerland.
authors.forename: Sandro
authors.initials: S
authors.lastname: Luescher
authors.affiliation: Hochschule Weihenstephan Triesdorf, University of Applied Sciences , Schulgasse 16, 94315 Straubing, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Urmann
authors.affiliation: Institute for Pharma Technology, School of Life Sciences, University of Applied Sciences Northwestern Switzerland , Gruendenstrasse 40, 4132 Muttenz, Switzerland.
authors.forename: Veronika
authors.identifier: 0000-0001-7516-8789
authors.initials: V
authors.lastname: Butterweck
mesh_terms: D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects; D044950:Flavanones / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D027582:Humulus / Q000737:chemistry / Q000378:metabolism*; D016898:Interferon-alpha / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D010539:Permeability / Q000187:drug effects; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D054876:Prenylation; D011427:Propiophenones / Q000494:pharmacology; D019108:Tight Junctions / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D044004:Xanthones / Q000494:pharmacology
chemical_list: C119737:8-prenylnaringenin; D044950:Flavanones; D005419:Flavonoids; D016898:Interferon-alpha; D010636:Phenols; D011427:Propiophenones; D014409:Tumor Necrosis Factor-alpha; D044004:Xanthones; C512910:isoxanthohumol; C104536:xanthohumol