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

1. 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.

2. 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.

3. In the transport experiment, P_app (AP-BL) was between 0.1 and 1.0?×?10⁶ 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.

4. At a concentration of 1–100 μM, berberine, palmatine, jateorhizine, and coptisine had no significant effects on the bidirection transport of Rho123.

5. Berberine, palmatine, jateorhizine, and coptisine were all P-gp substrates; and at the range of 1–100 μM, berberine, palmatine, jateorhizine, and coptisine had no inhibitory effects on P-gp.