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.

Attached Files
Name Description MIMEType Size Downloads

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
Total pages 22
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
Connect to link resolver
 
Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved.

Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 17 times in TR Web of Science
Scopus Citation Count Cited 17 times in Scopus
Google Scholar Search Google Scholar
Access Statistics: 69 Abstract Views, 2 File Downloads  -  Detailed Statistics
Created: Wed, 22 Feb 2012, 11:17:11 EST by Jane Moschetti

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.