Regulation of human pregnane X receptor and its target gene cytochrome P450 3A4 by Chinese herbal compounds and a molecular docking study

Regulation of human pregnane X receptor and its target gene cytochrome P450 3A4 by Chinese herbal compounds and a molecular docking study

Liu, Ya-He, Mo, Sui-Lin, Bi, Hui-Chang, Hu, Bing-Fang, Li, Chun Guang, Wang, Yi-Tao, Huang, Ling, Huang, Min, Duan, Wei, Liu, Jun-Ping, Wei, Ming Qian and Zhou, Shu-Feng 2011, Regulation of human pregnane X receptor and its target gene cytochrome P450 3A4 by Chinese herbal compounds and a molecular docking study, Xenobiotica, vol. 41, no. 4, pp. 259-280.

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Title	Regulation of human pregnane X receptor and its target gene cytochrome P450 3A4 by Chinese herbal compounds and a molecular docking study
Author(s)	Liu, Ya-He Mo, Sui-Lin Bi, Hui-Chang Hu, Bing-Fang Li, Chun Guang Wang, Yi-Tao Huang, Ling Huang, Min Duan, Wei Liu, Jun-Ping Wei, Ming Qian Zhou, Shu-Feng
Journal name	Xenobiotica
Volume number	41
Issue number	4
Start page	259
End page	280
Publisher	Informa Healthcare
Place of publication	London, U. K.
Publication date	2011-04
ISSN	0049-8254 1366-5928
Keyword(s)	PXR CYP3A4 induction herbal medicine herb–drug interaction
Summary	1. The pregnane X receptor (PXR) plays a critical role in the regulation of human cytochrome P450 3A4 (CYP3A4) gene. In this study, we investigated the effect of an array of compounds isolated from Chinese herbal medicines on the activity of PXR using a luciferase reporter gene assay in transiently transfected HepG2 and Huh7 cells and on the expression of PXR and CYP3A4 in LS174T cells. Furthermore, molecular docking was performed to investigate the binding modes of herbal compounds with PXR. 2. Praeruptorin A and C, salvianolic acid B, sodium danshensu, protocatechuic aldehyde, cryptotanshinone, emodin, morin, and tanshinone IIA significantly transactivated the CYP3A4 reporter gene construct in either HepG2 or Huh7 cells. The PXR mRNA expression in LS174T cells was significantly induced by physcion, protocatechuic aldehyde, salvianolic acid B, and sodium danshensu. However, epifriedelanol, morin, praeruptorin D, mulberroside A, tanshinone I, and tanshinone IIA significantly down-regulated the expression of PXR mRNA in LS174T cells. 3. All the herbal compounds tested can be readily docked into the ligand-binding cavity of PXR mainly through hydrogen bond and aromatic interactions with Ser247, Gln285, His407, and Arg401. 4. These findings suggest that herbal medicines can significantly regulate PXR and CYP3A4 and this has important implication in herb–drug interactions.
Language	eng
Field of Research	111204 Cancer Therapy (excl Chemotherapy and Radiation Therapy)
Socio Economic Objective	920101 Blood Disorders
HERDC Research category	C1 Refereed article in a scholarly journal
ERA Research output type	C Journal article
Copyright notice	©2011, Informa UK, Ltd.
Persistent URL	http://hdl.handle.net/10536/DRO/DU:30042590

Document type:	Journal Article
Collection:	School of Medicine

Citation counts:	Cited 9 times in TR Web of Science Cited 10 times in Scopus
Access Statistics:	35 Abstract Views, 1 File Downloads - Detailed Statistics
Created:	Wed, 22 Feb 2012, 11:17:11 EST by Jane Moschetti

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