Please use this identifier to cite or link to this item: https://doi.org/10.1124/dmd.106.010801
Title: Role of P-glycoprotein in the intestinal absorption of glabridin, an active flavonoid from the root of Glycyrrhiza glabra
Authors: Cao, J.
Chen, X.
Liang, J.
Yu, X.-Q.
Xu, A.-L.
Chan, E. 
Duan, W.
Huang, M.
Wen, J.-Y.
Yu, X.-Y.
Li, X.-T.
Sheu, F.-S. 
Zhou, S.-F.
Issue Date: Apr-2007
Citation: Cao, J., Chen, X., Liang, J., Yu, X.-Q., Xu, A.-L., Chan, E., Duan, W., Huang, M., Wen, J.-Y., Yu, X.-Y., Li, X.-T., Sheu, F.-S., Zhou, S.-F. (2007-04). Role of P-glycoprotein in the intestinal absorption of glabridin, an active flavonoid from the root of Glycyrrhiza glabra. Drug Metabolism and Disposition 35 (4) : 539-553. ScholarBank@NUS Repository. https://doi.org/10.1124/dmd.106.010801
Abstract: Glabridin is a major constituent of the root of Glycyrrhiza glabra, which is commonly used in the treatment of cardiovascular and central nervous system diseases. This study aimed to investigate the role of P-glycoprotein (PgP/MDR1) in the intestinal absorption of glabridin. The systemic bioavailability of glabridin was approximately 7.5% in rats, but increased when combined with verapamil. In single-pass perfused rat ileum with mesenteric vein cannulation, the permeability coefficient of glabridin based on drug disappearance in luminal perfusates (Plumen) was approximately 7-fold higher than that based on drug appearance in the blood (Pblood). Glabridin was mainly metabolized by glucuronidation, and the metabolic capacity of intestine microsomes was 1/15 to 1/20 of that in liver microsomes. Polarized transport of glabridin was found in Caco-2 and MDCKII monolayers. Addition of verapamil in both apical (AP) and basolateral (BL) sides abolished the polarized transport of glabridin across Caco-2 cells. Incubation of verapamil significantly altered the intracellular accumulation and efflux of glabridin in Caco-2 cells. The transport of glabridin in the BL-AP direction was significantly higher in MDCKII cells overexpressing PgP/MDR1 than in the control cells. Glabridin inhibited PgP-mediated transport of digoxin with an IC50 value of 2.56 μM, but stimulated PgP/MDR1 ATPase activity with a Km of 25.1 μM. The plasma AUC0-24h of glabridin in mdr1a(-/-) mice was 3.8-fold higher than that in wild-type mice. These findings indicate that glabridin is a substrate for PgP and that both PgP/MDR1-mediated efflux and first-pass metabolism contribute to the low oral bioavailability of glabridin. Copyright © 2007 by The American Society for Pharmacology and Experimental Therapeutics.
Source Title: Drug Metabolism and Disposition
URI: http://scholarbank.nus.edu.sg/handle/10635/101611
ISSN: 00909556
DOI: 10.1124/dmd.106.010801
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

59
checked on Oct 16, 2019

WEB OF SCIENCETM
Citations

47
checked on Oct 16, 2019

Page view(s)

67
checked on Oct 12, 2019

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.