Linked Life Data

20641061

Source:http://linkedlifedata.com/resource/pubmed/id/20641061

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-2-2
pubmed:abstractText
Corynoline, an isoquinoline alkaloid isolated from the genus Corydalis, has been demonstrated to show multiple pharmacological effects including inhibition of acetylcholinesterase, inhibition of cell adhesion, fungitoxic and cytotoxic activity. The present study focused on its metabolism and metabolism-based herb-drug interactions. After corynoline was incubated with human liver microsomes (HLMs) in the presence of NADPH, two metabolites (M-1 and M-2) were formed. Chemical inhibition experiments and assays with recombinant CYP isoforms showed that CYP2C9 was mainly involved in the formation of M-1 and CYP3A4 mainly catalysed the production of M-2. Among seven major CYP isoforms tested, corynoline showed strong inhibitory effects on the activities of CYP3A4 and CYP2C9, with an IC(50) of 3.3 ± 0.9?µm and 31.5 ± 0.5?µm, respectively. Kinetic analysis showed that inhibition of CYP3A4 by corynoline was best fit to a noncompetitive manner with K(i) of 3.2?µm, while inhibition of CYP2C9 by corynoline was best fit to a competitive manner with K(i) of 6.3?µm. Additionally, corynoline exhibited time-dependent inhibition (TDI) toward CYP3A4. The inactivation kinetic parameters (K(I) and k(inact) ) were calculated to be 6.8?µm and 0.07?min(-1) , respectively. These data are of significance for the application of corynoline and corynoline-containing herbs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1099-1573
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 John Wiley & Sons, Ltd.
pubmed:issnType
Electronic
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
256-63
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Identification of cytochrome P450 (CYP) isoforms involved in the metabolism of corynoline, and assessment of its herb-drug interactions.
pubmed:affiliation
Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't