Involvement of P-glycoprotein in regulating cellular levels of Ginkgo flavonols: quercetin, kaempferol, and isorhamnetin.
Quercetin, kaempferol, and isorhamnetin were the most important flavonoid constituents in extracts from Ginkgo biloba leaves. Transport studies of Ginkgo flavonols were performed in Caco-2 cell mono-layers. Their apparent permeability in absorptive and secretion directions was determined, and quercetin, kaempferol and isorhamnetin displayed polarized transport, with the Papp,B-A being higher than the Papp,A-B (P<0.01 for quercetin, P<0.001 for kaempferol and isorhamnetin, Student's t-test). Bcap37/MDR1 cells, which were transfected with a P-glycoprotein (P-gp) gene construct, were treated with quercetin, kaempferol or isorhamnetin. The concentrations of Ginkgo flavonol in Bcap37/MDR1 cells were lower than those in parent cells (P<0.05 for quercetin, P<0.01 for isorhamnetin, Mann-Whitney U test). The concentrations of the flavonol in transfected cells increased when incubated with the P-gp inhibitor verapamil (P<0.05 for kaempferol, Mann-WhitneyU test). A colorometric assay for ATPase activity was applied to the detection of interaction of flavonol with P-gp. Quercetin and kaempferol inhibited the ATPase activity, and isorhamnetin stimulated the ATPase activity (P<0.05 for isorhamnetin, Mann Whitney U test). The results indicated that Ginkgo flavonols quercetin, kaempferol and isorhamnetin were substrates of P-gp. The P-gp type efflux pump might limit the bioavailability of Ginkgo flavonols.
Wang
Yi
Y
Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, 310031, People's Republic of China.
Cao
Jiang
J
Zeng
Su
S
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D001692:Biological Transport; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability; D044948:Flavonols / Q000378:metabolism*; D020441:Ginkgo biloba; D006801:Humans; D044949:Kaempferols / Q000378:metabolism*; D000091402:Prohibitins; D011794:Quercetin / Q000378:metabolism* / Q000031:analogs & derivatives
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D044948:Flavonols; D044949:Kaempferols; C000717331:PHB2 protein, human; D000091402:Prohibitins; C047368:3-methylquercetin; C006552:kaempferol; D011794:Quercetin; D000251:Adenosine Triphosphatases