title: Intestinal absorption mechanisms of berberine, palmatine, jateorhizine, and coptisine: involvement of P-glycoprotein.
abstract: 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 (MRP(2)) 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 × 10(6) 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 μM, 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 μM, berberine, palmatine, jateorhizine, and coptisine had no inhibitory effects on P-gp.
authors.affiliation: Department of Clinical Pharmacology, Shuguang Hospital Affiliated to Shanghai University of TCM, Shanghai, China.
authors.forename: Xinfeng
authors.initials: X
authors.lastname: Zhang
authors.forename: Furong
authors.initials: F
authors.lastname: Qiu
authors.forename: Jian
authors.initials: J
authors.lastname: Jiang
authors.forename: Chenglu
authors.initials: C
authors.lastname: Gao
authors.forename: Yingzi
authors.initials: Y
authors.lastname: Tan
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001599:Berberine / Q000031:analogs & derivatives / Q000378:metabolism; D001600:Berberine Alkaloids / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D018938:Caco-2 Cells; D016572:Cyclosporine / Q000378:metabolism / Q000494:pharmacology; D004365:Drugs, Chinese Herbal / Q000378:metabolism*; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D011422:Propionates / Q000378:metabolism / Q000494:pharmacology; D011804:Quinolines / Q000378:metabolism / Q000494:pharmacology; D014700:Verapamil / Q000378:metabolism / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001599:Berberine; D001600:Berberine Alkaloids; D016572:Cyclosporine; D004365:Drugs, Chinese Herbal; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011422:Propionates; D011804:Quinolines; D014700:Verapamil; C000715087:ABCC2 protein, human; C055785:jatrorrhizine; C034384:coptisine; C059141:verlukast; C005413:palmatine