CAR-mediated up-regulation of CYP3A4 expression in LS174T cells by chinese herbal compounds

Huang, L, Bi, H, Liu, Y, Wang, Y, Xue, X and Huang, M 2011, 'CAR-mediated up-regulation of CYP3A4 expression in LS174T cells by chinese herbal compounds ', Drug Metabolism And Pharmacokinetics , vol. 26, no. 4, pp. 331-340.


Document type: Journal Article
Collection: Journal Articles

Title CAR-mediated up-regulation of CYP3A4 expression in LS174T cells by chinese herbal compounds
Author(s) Huang, L
Bi, H
Liu, Y
Wang, Y
Xue, X
Huang, M
Year 2011
Journal name Drug Metabolism And Pharmacokinetics
Volume number 26
Issue number 4
Start page 331
End page 340
Total pages 10
Publisher Yakubutsu Dotai Gakkai
Abstract The constitutive androstane receptor (CAR) is an orphan nuclear receptor which has been shown to participate in the activation of human CYP3A4, which metabolizes more than 50% of clinically used drugs. We investigated the effects of an array of compounds isolated from herbal medicines such as Rheum palmatum (Da Huang), Peucedanum praeruptorum Dunn (Qian Hu), Cortex Mori Radicis (Sang Bai Pi), Radix Asteris (Zi Wan), Salvia miltiorrhiza (Dan Shen), Polygonum cuspidatum Sieb. et Zucc (Hu Zhang), and Ginkgo biloba (Yin Xing) on the CAR-mediated transactivation of CYP3A4. The effect of herbal compounds on CYP3A4 expression was measured using a CYP3A4 luciferase reporter gene assay in transiently transfected human intestinal LS174T cells. The gene expression, protein expression, and catalytic activity of CYP3A4 in LS174T cells transfected with CAR were determined by using real-time PCR, Western blot analysis, and LC-MS/MS-based substrate assay. The study found that in CAR-transfected cells, praeruptorin A, C, and D significantly induced CYP3A4 luciferase activity, mRNA expression, and functional activity through the CAR-mediated pathway; conversely, induction was not found in untransfected cells. Our findings suggest that these herbal compounds can significantly up-regulate the CYP3A4 gene via the CAR-mediated pathway, which has important implications in herbdrug interactions.
Keyword(s) Constitutive androstane receptor (CAR)
Cytochrome P450 3A4
Herb compounds
Herbdrug interaction
Induction
luciferase
messenger RNA
plant medicinal product
praeruption A
praeruption C
praeruption D
unclassified drug
article
Chinese herb
constitutive androstane receptor gene
controlled study
cytochrome P450 3A4 gene
Da Huang
drug determination
drug effect
enzyme activity
gene
gene activation
gene expression profiling
gene expression regulation
gene induction
herb drug interaction
Hu Zhang
human
human cell
mulberry
peucedanum praeruptorum
physical chemistry
phytochemistry
protein expression
reporter gene
Salvia miltiorrhiza
signal transduction
transactivation
transcription regulation
transient transfection
upregulation
Yin Xing
Zi Wan
alcium Channel Blockers
Cell Line
Tumor
Coumarins
Cytochrome P-450 CYP3A
Drugs
Chinese Herbal
Enzyme Induction
Gene Expression
Genes
Reporter
Humans
Luciferases
Nifedipine
Plasmids
Receptors
Cytoplasmic and Nuclear
RNA
RNA
Messenger
Transcriptional Activation
Transfection
Up-Regulation
DOI - identifier 10.2133/dmpk.DMPK-10-RG-115
Copyright notice © 2011 The Japanese Society for the Study of Xenobiotics (JSSX
ISSN 1347-4367
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Citation counts: TR Web of Science Citation Count  Cited 24 times in Thomson Reuters Web of Science Article | Citations
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