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.

Green tea extracts (GTE) might modulate ABC transporter gene expression or function. This may be relevant in the treatment of cancer or in influencing intestinal drug permeability. To gain more insight on the influence of a GTE on secretory transport proteins we investigated the influence of GTE and several green tea components on the mRNA expression level of P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (MRP2) in human gastrointestinal epithelial LS-180 cells. Furthermore, the functional activity of MRP2, using glutathione methylfluorescein (GS-MF) or [3H]methotrexate (MTX) as substrate, was investigated in canine kidney cells stably overexpressing human MRP2 (MDCK-MRP2). GTE, at a concentration of 0.01 mg/mL, did not increase mRNA expression of P-gp or MRP2 in LS-180 cells. Functional assays in MDCK-MRP2 cells using GS-MF did not show any effect of 0.01 mg/mL GTE on MRP2 activity. In the same cell line the cellular accumulation of MTX (a specific substrate of MRP2) was significantly increased with the MRP-specific inhibitor MK-571 or with 1 mg/mL GTE, but not with 0.1 mg/mL. The green tea components (-)-epigallocatechin gallate, (-)-epigallocatechin, theanine, or caffeine, each in corresponding concentrations to the respective concentration of GTE, did not show any effect on MRP2 function. These data demonstrate that the mRNA expression patterns of P-gp and MRP2 in LS-180 cells are not altered by 0.01 mg/mL of GTE. However, MRP2 function was inhibited by 1 mg/mL GTE, whereas none of the green tea components tested were responsible for this effect.

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