IngentaConnect Involvement of P-glycoprotein in regulating cellular levels of Gi...

Authors: Wang, Yi¹; Cao, Jiang²; Zeng, Su¹

Source: Journal of Pharmacy and Pharmacology, Volume 57, Number 6, June 2005 , pp. 751-758(8)

Abstract:

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 P_app,B-A being higher than the P_app,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.

Document Type: Research article

DOI: 10.1211/0022357056299

Affiliations: 1: Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, 310031, People's Republic of China 2: Clinical Research Institute, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, 310016, People's Republic of China

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Involvement of P-glycoprotein in regulating cellular levels of Ginkgo flavonols: quercetin, kaempferol, and isorhamnetin