Cytochrome P450-mediated herb-drug interaction potential of Galgeun-tang

Title
Cytochrome P450-mediated herb-drug interaction potential of Galgeun-tang
Author(s)
강원구이상윤[이상윤]이지윤[이지윤]권광일[권광일]박송규[박송규]오수진[오수진]마진열[마진열]김상겸[김상겸]
Keywords
IN-VITRO; MASS-SPECTROMETRY; RAT-LIVER; INHIBITION; EXPRESSION; INDUCTION; ENZYMES; ACID; METABOLISM; CELLS
Issue Date
201301
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Citation
FOOD AND CHEMICAL TOXICOLOGY, v.51, pp.343 - 349
Abstract
We evaluated the herb-drug interaction potential of Galgeun-tang (GGT) extracts, mediated by cytochrome P450 (CYP) inhibition/induction. Further, the effects of fermentation on the CYP-mediated herb-drug interaction potential of GGT extracts were determined. As measured by LC-ESI/MS/MS, GGT extracts (0-300 mu g/mL) showed no inhibitory activity toward eight CYP isoforms (1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, and 3A4) in pooled human liver microsomes, suggesting that GGT may have low potential for herb-drug interactions mediated by CYP inhibition. Hepatic CYP expression and activity in rats treated with GGT extracts twice per day for I week was examined. Among the tested CYP isoforms (1A1, 1A2, 1B1, 2B1, 2C11, 2E1, 3A1, 3A2, and 4A1), CYP1B1 and 4A1 were increased by GGT extracts. Hepatic activities of 7-ethoxyresorufin-O-deethylase, 7-pentoxyresorufin-O-depentylase, and chlorzoxazone 6-hydroxylase, but not midazolam hydroxylase were also elevated. These results raise the possibility that GGT extracts may increase the toxicity of environmental toxicants through the elevating CYP-dependent metabolic activation. Interestingly, the increases in CYPIBI and CYP4A1 levels, and 7-ethoxyresorufin-O-deethylase, 7-pentoxyresorufin-O-depentylase, and chlorzoxazone 6-hydroxylase activities were attenuated by fermentation of GGT extract using Lactobacillus plantarum KFRI 402, but not 144. Further studies are needed to identify the CYP regulatory component(s) from GGT and determination its metabolism. (C) 2012 Elsevier Ltd. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/26832http://dx.doi.org/10.1016/j.fct.2012.10.012
ISSN
0278-6915
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약학대학 > 약학부 > Articles
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