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Regulation of human pregnane X receptor and its target gene cytochrome P450 3A4 by Chinese herbal compounds and a molecular docking study
Liu, YH (Liu, Ya-He)2; Mo, SL (Mo, Sui-Lin)2,3; Bi, HC (Bi, Hui-Chang)4; Hu, BF (Hu, Bing-Fang)4; Li, CG (Li, Chun Guang)2; Wang, YT (Wang, Yi-Tao)5; Huang, L (Huang, Ling)4; Huang, M (Huang, Min)4; Duan, W (Duan, Wei)6; Liu, JP (Liu, Jun-Ping)7; Wei, MQ (Wei, Ming Qian)8; Zhou, SF (Zhou, Shu-Feng)1,2
2011-04
Source PublicationXENOBIOTICA
ISSN0049-8254
Volume41Issue:4Pages:259-280
Abstract

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. 

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. 

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. 

These findings suggest that herbal medicines can significantly regulate PXR and CYP3A4 and this has important implication in herb--drug interactions.

KeywordConstitutive Androstane Receptor Primary Human Hepatocytes Corepressor Silencing-mediator Hepatoma-cell Lines Human Cyp3a4 Gene Nuclear Receptor Drug-metabolism Transcriptional Activation Xenobiotic Receptor Interindividual Variability
DOI10.3109/00498254.2010.537395
WOS IDWOS:000288552700001
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Cited Times [WOS]:34   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Univ S Florida, Dept Pharmaceut Sci, Coll Pharm, Tampa, FL 33612 USA
2.RMIT Univ, Sch Hlth Sci & Hlth Innovat, Res Inst, Bundoora, Vic, Australia
3.Sun Yet Sen Univ, Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China
4.Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510275, Guangdong, Peoples R China
5.Univ Macau, Inst Chinese Med Sci, Macao, Peoples R China
6.Deakin Univ, Sch Med, Waurn Ponds, Vic, Australia
7.Monash Univ, Dept Immunol, Cent & Eastern Clin Sch, Prahran, Vic, Australia
8.Griffith Univ, Div Mol Med & Gene Therapy, Sch Med Sci, Southport, Qld 4215, Australia
Recommended Citation
GB/T 7714
Liu, YH ,Mo, SL ,Bi, HC ,et al. Regulation of human pregnane X receptor and its target gene cytochrome P450 3A4 by Chinese herbal compounds and a molecular docking study[J]. XENOBIOTICA,2011,41(4):259-280.
APA Liu, YH .,Mo, SL .,Bi, HC .,Hu, BF .,Li, CG .,...&Zhou, SF .(2011).Regulation of human pregnane X receptor and its target gene cytochrome P450 3A4 by Chinese herbal compounds and a molecular docking study.XENOBIOTICA,41(4),259-280.
MLA Liu, YH ,et al."Regulation of human pregnane X receptor and its target gene cytochrome P450 3A4 by Chinese herbal compounds and a molecular docking study".XENOBIOTICA 41.4(2011):259-280.
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