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® 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 (Papp) of these two compounds in the secretory direction was larger than that in the absorptive direction in the concentration range of 10–1000 μM. 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.