| Inhibitory effects of deoxypodophyllotoxin from Anthriscus sylvestris on human CYP2C9 and CYP3A4. | |
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MedLine Citation:
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PMID: 19960413 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Deoxypodophyllotoxin (DPT) is a bioactive compound of Anthriscus sylvestris (Apiaceae). In the present study, the inhibition of cytochrome P450 (CYP) by DPT was evaluated in human liver microsomes (HLM) and the baculovirus-insect cell-expressed human CYPs using a cocktail probe assay. When a mixture of specific CYP substrates was incubated with DPT in HLM, CYP2C9-catalyzed diclofenac 4-hydroxylation and CYP3A4-catalyzed midazolam 1-hydroxylation were strongly inhibited by DPT, with IC (50) values of 6.3 and 9.2 microM, respectively. The Lineweaver-Burke plots for the inhibition of CYP2C9 and CYP3A4 in HLM and baculovirus-insect cell-expressed human CYPs were consistent with a competitive type of inhibition. From these results, DPT was characterized to be a competitive inhibitor of CYP2C9 and CYP3A4, with K(i) values of 3.5 and 10.8 microM in HLM and 24.9 and 3.5 microM in baculovirus-insect cell-expressed human CYPs, respectively. |
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Authors:
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Sang Kyu Lee; Yoon Kim; Changbae Jin; Seung Ho Lee; Mi Jeong Kang; Tae Cheon Jeong; Seo Young Jeong; Dong-Hyun Kim; Hye Hyun Yoo |
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Publication Detail:
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Type: Letter; Research Support, Non-U.S. Gov't Date: 2009-12-03 |
Journal Detail:
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Title: Planta medica Volume: 76 ISSN: 1439-0221 ISO Abbreviation: Planta Med. Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-05-06 Completed Date: 2010-10-26 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0066751 Medline TA: Planta Med Country: Germany |
Other Details:
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Languages: eng Pagination: 701-4 Citation Subset: IM |
Copyright Information:
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Georg Thieme Verlag KG Stuttgart. New York. |
Affiliation:
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Doping Control Center, Korea Institute of Science and Technology, Chungryang, Seoul 130-650, Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apiaceae* Aryl Hydrocarbon Hydroxylases / antagonists & inhibitors* Cytochrome P-450 CYP3A / antagonists & inhibitors* Drug Evaluation, Preclinical Humans Microsomes, Liver Podophyllotoxin / analogs & derivatives*, pharmacology |
| Chemical | |
Reg. No./Substance:
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518-28-5/Podophyllotoxin; 69222-20-4/deoxypodophyllotoxin; EC 1.14.13.67/CYP3A4 protein, human; EC 1.14.14.1/Aryl Hydrocarbon Hydroxylases; EC 1.14.14.1/CYP2C9 protein, human; EC 1.14.14.1/Cytochrome P-450 CYP3A |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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