Permeation of astilbin and taxifolin in Caco-2 cell and their effects on the P-gp

This study was designed to understand the transport profiles of astilbin and taxifolin in Caco-2 cell model and their effects on the function and expression of P-glycoprotein. The transport studies were examined using Caco-2 cells cultured on Transwell (R) inserts. Their effects on the function and expression of P-glycoprotein were detected using Western Blot and RT-PCR. The transport was concentration and temperature dependent. The apparent permeability (P-app) of these two compounds in the secretory direction was larger than that in the absorptive direction in the concentration range of 10-1000 mu M. Those compounds had no effects on the P-glycoprotein-mediated transport of Rhodamine 123. Caco-2 cells exposed to astilbin or taxifolin for 36 h exhibited higher P-glycoprotein activity through up-regulating P-glycoprotein expression at protein and mRNA levels. These results indicated that P-glycoprotein and Multidrug Resistance Protein 2 might play important roles in limiting the bioavailability of those compounds. Drugs which are the inhibitors of P-glycoprotein or Multidrug Resistance Protein 2 may increase the oral bioavailability of astilbin or taxifolin and the possibility of unwanted drug-food interactions. The increased expression of P-glycoprotein in Caco-2 cells may serve as an adaptation and defense mechanism in limiting the entry of xenobiotics into the body. (C) 2009 Elsevier B.V. All rights reserved.