Linked Life Data

12857935

Source:http://linkedlifedata.com/resource/pubmed/id/12857935

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-8-18
pubmed:abstractText
This study in mice investigated whether hyperforin accounts for the inductive effects on cytochrome P4503A enzymes of St. John's wort extracts (SJW; Hypericum perforatum), one of the most popular herbal preparations because of its alleged activity in mild to moderate depression. A hydroalcoholic extract containing 4.5% hyperforin was given at a dose of 300 mg/kg, bis in die (b.i.d.), for 4 and 12 days. Hyperforin, its main phloroglucinol component, was given as dicyclohexylammonium (DCHA) salt (18.1 mg/kg, b.i.d.) on the basis of its content in the extract, to ensure comparable exposure to hyperforin. The extract increased hepatic erythromycin-N-demethylase (ERND) activity, which is cytochrome P450 enzyme (CYP) 3A-dependent, about 2.2-fold after 4 days of dosing, with only slightly greater effect after 12 days (2.8 times controls). Hyperforin too increased ERND activity within 4 days, much to the same extent as the extract (1.8 times the activity of controls), suggesting that it behaves qualitatively and quantitatively like the extract as regards induction of CYP3A activity. This effect was confirmed by Western blot analysis of hepatic CYP3A expression. Exposure to hyperforin at the end of the 4-day treatment was still similar to that with SJW extract, although it was variable and lower than after the first dose in both cases, further suggesting that hyperforin plays a key role in CYP3A induction by the SJW extract in the mouse. Standardization of the extracts based on the hyperforin content can be proposed for further evaluation of their potential action on first-pass metabolism and clearance of coadministered CYP3A substrates.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1096-6080
pubmed:author
pubmed:issnType
Print
pubmed:volume
75
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
25-30
pubmed:dateRevised
2010-9-17
pubmed:meshHeading
pubmed-meshheading:12857935-Administration, Oral, pubmed-meshheading:12857935-Animals, pubmed-meshheading:12857935-Area Under Curve, pubmed-meshheading:12857935-Aryl Hydrocarbon Hydroxylases, pubmed-meshheading:12857935-Bicyclo Compounds, pubmed-meshheading:12857935-Blotting, Western, pubmed-meshheading:12857935-Cytochrome P-450 CYP3A, pubmed-meshheading:12857935-Dose-Response Relationship, Drug, pubmed-meshheading:12857935-Hypericum, pubmed-meshheading:12857935-Male, pubmed-meshheading:12857935-Mice, pubmed-meshheading:12857935-Mice, Inbred Strains, pubmed-meshheading:12857935-Microsomes, Liver, pubmed-meshheading:12857935-Oxidoreductases, N-Demethylating, pubmed-meshheading:12857935-Phloroglucinol, pubmed-meshheading:12857935-Plant Extracts, pubmed-meshheading:12857935-Terpenes, pubmed-meshheading:12857935-Time Factors
pubmed:year
2003
pubmed:articleTitle
Hyperforin contributes to the hepatic CYP3A-inducing effect of Hypericum perforatum extract in the mouse.
pubmed:affiliation
Istituto di Ricerche Farmacologiche Mario Negri, Via Eritrea 62, 20157 Milan, Italy. cantoni@marionegri.it
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't