Intestinal absorption mechanisms of berberine, palmatine, jateorhizine, and coptisine: involvement of P-glycoprotein

The absorption and transport mechanisms of berberine, palmatine, jateorhizine, and coptisine were studied using a Caco-2 cells uptake and transport model, with the addition of cyclosporin A and verapamil as P-glycoprotein (P-gp) inhibitors and MK-571 as a multidrug resistance-associated protein 2 (MRP2) inhibitor. In the uptake experiment, berberine, palmatine, jateorhizine, and coptisine were all taken into Caco-2 cells, and their uptakes were increased in the presence of cyclosporin A or verapamil. In the transport experiment, P-app (AP-BL) was between 0.1 and 1.0 xx 10<SU6</SU cm/sec for berberine, palmatine, jateorhizine, and coptisine and was lower than P-app (BL-AB). ER values were all > 2. Cyclosporin A and verapamil both increased P-app (AP-BL) but decreased P-app (BL-AB) for berberine, palmatine, jateorhizine, and coptisine; ER values were decreased by > 50%. MK-571 had no influence on the transmembrane transport of berberine, palmatine, jateorhizine, and coptisine. At a concentration of 1--100 mu mu M, berberine, palmatine, jateorhizine, and coptisine had no significant effects on the bidirection transport of Rho123. Berberine, palmatine, jateorhizine, and coptisine were all P-gp substrates; and at the range of 1--100 mu mu M, berberine, palmatine, jateorhizine, and coptisine had no inhibitory effects on P-gp.