Inhibitory effects of Hwang-Ryun-Hae-Dok-Tang on cytochrome P450 in human liver microsomes

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Title
Inhibitory effects of Hwang-Ryun-Hae-Dok-Tang on cytochrome P450 in human liver microsomes
Author(s)
S Y Lee; H Jang; J Y Lee; J Y Ma; Soo Jin Oh; S K Kim
Bibliographic Citation
Xenobiotica, vol. 45, no. 2, pp. 131-138
Publication Year
2015
Abstract
1.The herb-drug interaction potential of Hwang-Ryun-Hae-Dok-Tang (HR) extracts mediated by cytochrome P450 (CYP) inhibition was determined using human liver microsomes. 2.HR strongly inhibited CYP1A2 and moderately inhibited CYP2C19, CYP2D6, and CYP3A4 (testosterone) but not CYP2A6, CYP2B6, CYP2C8, CYP2C9, and CYP3A4 (midazolam). 3.The enzyme kinetic results suggest that CYP1A2 inhibition is competitively reversible (Ki, 13.4±1.8μg/ml), and CYP2D6 inhibition is quasi-irreversible (KI, 0.234±0.138μg/ml; kinact, 0.067±0.006min-1). 4.Fermentation using Lactobacillus acidophilus attenuated the HR-induced inhibition of CYP2D6, but not the other isoforms. 5.Neither CYP1A2 nor CYP3A4 was markedly inhibited by berberine, palmatine, and geniposide major components in HR and CYP2D6 was inhibited by berberine (IC50, 13.8μg/ml) in a metabolism-dependent manner. 6.The results suggest the possibility of HR-drug interaction through inhibition of CYP particularly CYP2D6 which may be attenuated by fermentation using L. acidophilus.
Keyword
FermentationHerb-drug interactionHwang-Ryun-Hae-Dok-TangCytochrome P450
ISSN
0049-8254
Publisher
T&F (Taylor & Francis)
DOI
http://dx.doi.org/10.3109/00498254.2014.953624
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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