Please use this identifier to cite or link to this item: https://doi.org/10.1124/dmd.107.019737
Title: Effects of spice constituents on P-glycoprotein-mediated transport and CYP3A4-mediated metabolism in vitro
Authors: Zhang, W. 
Lim, L.-Y. 
Issue Date: Jul-2008
Citation: Zhang, W., Lim, L.-Y. (2008-07). Effects of spice constituents on P-glycoprotein-mediated transport and CYP3A4-mediated metabolism in vitro. Drug Metabolism and Disposition 36 (7) : 1283-1290. ScholarBank@NUS Repository. https://doi.org/10.1124/dmd.107.019737
Abstract: The effects of eight components from six commonly consumed spices on P-glycoprotein (P-gp) transport and CYP3A4 metabolism were evaluated in vitro. P-gp-mediated [3H]digoxin fluxes across the L-MDR1 (LLC-PK1 cells transfected with human MDR1 gene) and Caco-2 (human colon carcinoma) cell monolayers showed a marked asymmetry compared with that in the LLC-PK1 (porcine kidney epithelial cells) cell monolayers. Curcumin (from turmeric) at 30 to 60 μM and 6-gingerol (from ginger) at 100 to 500 μM were observed to inhibit P-gp-mediated [3H]digoxin transport in L-MDR1 and Caco-2 cells. Effects of spices on midazolam (MDZ) 1′-hydroxylation and 4-hydroxylation of CYP3A4 activity were determined in pooled human liver microsomes (HLM). The following IC50 values for effects of spices on MDZ 1′-hydroxylation in HLM were obtained: 29 μM for curcumin, 1.17 mM for allyl methyl disulfide (AMD) (from Chinese chive), 1.02 mM for 1,8-cineole (from coriander), and 1.28 mM for β-caryophyllene (from curry leaf). CYP3A4-mediated 4-hydroxylation of MDZ was inhibited by curcumin at 30, 45, and 60 μM (4-hydroxy-MDZ formation was decreased to 52, 30, and 29%, respectively, compared with control), by 6-gingerol at 60, 100, and 500 μM (71, 68, and 38%), by AMD at 1 and 4 mM (29 and 14%), by d-limonene (from coriander) at 4 mM (65%), by 1,8-cineole at 0.5, 1, and 4 mM (74, 64, and 59%), and by citral (from lemon-grass) at 1 mM (59%). Among the spices that showed inhibitory effect on MDZ metabolism in HLM, only AMD showed a preincu-bation time-dependent inhibitory effect on MDZ metabolism in HLM, suggesting the AMD as an irreversible CYP3A4 inhibitor. Copyright © 2008 by The American Society for Pharmacology and Experimental Therapeutics.
Source Title: Drug Metabolism and Disposition
URI: http://scholarbank.nus.edu.sg/handle/10635/105906
ISSN: 00909556
DOI: 10.1124/dmd.107.019737
Appears in Collections:Staff Publications

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

SCOPUSTM   
Citations

61
checked on Aug 18, 2018

WEB OF SCIENCETM
Citations

51
checked on Jul 25, 2018

Page view(s)

31
checked on Aug 17, 2018

Google ScholarTM

Check

Altmetric


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