Transport of hop bitter acids across intestinal Caco-2 cell monolayers

Several health-beneficial properties of hop bitter acids have been reported; however, scientific data on the bioavailability of these compounds are lacking. As a first approach to study the bioavailability, the epithelial transport of hop α- and β-acids across Caco-2 monolayers was investigated. Hop acids were added either to the apical or to the basolateral chamber and, at various time points, amounts transported to the receiving compartment were determined. The monolayer integrity control was performed by using marker compounds (atenolol and propranolol), transepithelial electrical resistance (TEER) measurement, and determination of the fluorescein efflux. The TEER and fluorescein efflux confirmed the preservation of the monolayer integrity. The membrane permeability of the α-acids (apparent permeability coefficients for apical to basolateral transport (PappAB) ranged from 14 x 10-6 to 41 x 10-6 cm/s) was determined to be substantially higher than that of the β-acids (PappAB values ranging from 0.9 x 10-6 to 2.1 x 10-6 cm/s). Notably, the β-acids exhibited significantly different bidirectional Papp values with efflux ratios around 10. The involvement of carrier-mediated transport for β-acids (active efflux pathway by P-gp, BCRP, and/or MRP-2 type efflux pumps) could be confirmed by transport experiments with specific inhibitors (verapamil and indomethacin). It appears that R-acids are efficiently absorbed, whereas the permeability of β-acids is low. Limiting factors in the absorption of β-acids could involve P-gp and MRP-2 type efflux transporters and phase II metabolism