Linked Life Data

16267138

Source:http://linkedlifedata.com/resource/pubmed/id/16267138

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2006-2-23
pubmed:abstractText
The traditional Chinese medicines (TCMs) are essential components of alternative medicines. Many TCMs are known to alter the expression of hepatic drug-metabolizing enzymes and transporters. The molecular mechanism by which TCMs and/or their constituents regulate enzyme and transporter expression, however, has remained largely unknown. In this report, we show that two TCMs, Wu Wei Zi (Schisandra chinensis Baill) and Gan Cao (Glycyrrhiza uralensis Fisch), and their selected constituents activate the xenobiotic orphan nuclear receptor pregnane X receptor (PXR). Treatment with TCM extracts and the Schisandrol and Schisandrin constituents of Wu Wei Zi induced the expression of drug-metabolizing enzymes and transporters in reporter gene assays and in primary hepatocyte cultures. The affected enzymes and transporters include CYP3A and 2C isozymes and the multidrug resistance-associated protein 2. In transient transfection and reporter gene assays, the Schisandrin constituents of Wu Wei Zi had an estimated EC50 of 2 and 1.25 microM on hPXR and mPXR, respectively. Interestingly, mutations that were intended to alter the pore of the ligand-binding cavity of PXR had species-specific effects on the activities of the individual Schisandrols and Schisandrins. In rats, the administration of Wu Wei Zi and Gan Cao increased the metabolism of the coadministered warfarin, reinforcing concerns involving the safe use of herbal medicines and other nutraceuticals to avoid PXR-mediated drug-drug interactions. Meanwhile, the activation of PXR and induction of detoxifying enzymes provide a molecular mechanism for the hepatoprotective effects of certain TCMs.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
316
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1369-77
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:16267138-Animals, pubmed-meshheading:16267138-Cells, Cultured, pubmed-meshheading:16267138-Enzyme Induction, pubmed-meshheading:16267138-Glycyrrhiza uralensis, pubmed-meshheading:16267138-Hepatocytes, pubmed-meshheading:16267138-Humans, pubmed-meshheading:16267138-Male, pubmed-meshheading:16267138-Medicine, Chinese Traditional, pubmed-meshheading:16267138-Metabolic Clearance Rate, pubmed-meshheading:16267138-Mice, pubmed-meshheading:16267138-Plant Extracts, pubmed-meshheading:16267138-Rats, pubmed-meshheading:16267138-Rats, Sprague-Dawley, pubmed-meshheading:16267138-Receptors, Cytoplasmic and Nuclear, pubmed-meshheading:16267138-Receptors, Steroid, pubmed-meshheading:16267138-Schisandra, pubmed-meshheading:16267138-Species Specificity, pubmed-meshheading:16267138-Warfarin
pubmed:year
2006
pubmed:articleTitle
Traditional Chinese medicines Wu Wei Zi (Schisandra chinensis Baill) and Gan Cao (Glycyrrhiza uralensis Fisch) activate pregnane X receptor and increase warfarin clearance in rats.
pubmed:affiliation
Center for Pharmacogenetics, University of Pittsburgh School of Pharmacy, Pittsburgh, PA, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural