Role of P-glycoprotein in the intestinal absorption of glabridin, an active flavonoid from the root of Glycyrrhiza glabra

Cao, J, Chen, X, Liang, J, Yu, X, Xu, A, Chen, E, Duan, W, Huang, M, Wen, J, Yu, X, Li, X, Sheu, F and Zhou, S 2007, 'Role of P-glycoprotein in the intestinal absorption of glabridin, an active flavonoid from the root of Glycyrrhiza glabra', Drug Metabolism and Disposition, vol. 35, no. 4, pp. 539-553.


Document type: Journal Article
Collection: Journal Articles

Title Role of P-glycoprotein in the intestinal absorption of glabridin, an active flavonoid from the root of Glycyrrhiza glabra
Author(s) Cao, J
Chen, X
Liang, J
Yu, X
Xu, A
Chen, E
Duan, W
Huang, M
Wen, J
Yu, X
Li, X
Sheu, F
Zhou, S
Year 2007
Journal name Drug Metabolism and Disposition
Volume number 35
Issue number 4
Start page 539
End page 553
Total pages 15
Publisher American Society for Pharmacology and Experimental Therapeutics
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.
DOI - identifier 10.1124/dmd.106.010801
ISSN 0090-9556
Versions
Version Filter Type
Citation counts: Scopus Citation Count Cited 50 times in Scopus Article | Citations
Altmetric details:
Access Statistics: 106 Abstract Views  -  Detailed Statistics
Created: Mon, 06 Dec 2010, 14:11:00 EST by Catalyst Administrator
© 2014 RMIT Research Repository • Powered by Fez SoftwareContact us