The Involvement of P‐Glycoprotein in Berberine Absorption

Berberine is an important ingredient in a number of traditional Chinese medicines but has been shown to have poor bioavailability in the dog. The aim of this study was to use the P-glycoprotein (P-glycoprotein) inhibitors cyclosporin A, verapamil and the monoclonal antibody C219 in in vivo and in vitro models of intestinal absorption to determine the role of P-glycoprotein in berberine absorption. In the rat recirculating perfusion model, berberine absorption was improved 6-times by P-glycoprotein inhibitors. In the rat everted intestinal sac model, berberine serosal-to-mucosal transport was significantly decreased by cyclosporin A. In Ussing-type chambers, the rate of serosal-to-mucosal transport across rat ileum was 3-times greater than in the reverse direction and was significantly decreased by cyclosporin A. In Caco-2 cells, berberine uptake was significantly increased by P-glycoprotein inhibitors and by monoclonal antibody C219. P-glycoprotein appears to contribute to the poor intestinal absorption of berberine which suggests P-glycoprotein inhibitors could be of therapeutic value by improving its bioavailability.