Inhibitory Effects of Deoxypodophyllotoxin from Anthriscus sylvestris on Human CYP2C9 and CYP3A4

Title
Inhibitory Effects of Deoxypodophyllotoxin from Anthriscus sylvestris on Human CYP2C9 and CYP3A4
Authors
이상규김윤진창배이승호강미정정태천정서영김동현유혜현
Keywords
Deoxypodophyllotoxin; cytochrome P450; competitive inhibition; cocktail probe assay; Anthriscus sylvestris; Apiaceae
Issue Date
2010-05
Publisher
Planta medica
Citation
VOL 76, NO 7, 701-704
Abstract
Deoxypodophyllotoxin (DPT) is a bioactive compound of Anthriscus sylvestris (Apiaceae). In the present study, the inhibition of cytochrome P450 (CYP) by DPTwas evaluated in human liver microsomes (HLM) and the baculovirus-insect cell-expressed human CYPs using a cocktail probe assay. When amixture 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 IC50 values of 6.3 and 9.2 μM, 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, DPTwas characterized to be a competitive inhibitor of CYP2C9 and CYP3A4, with Ki values of 3.5 and 10.8 μM in HLM and 24.9 and 3.5 μM in baculovirus-insect cell-expressed human CYPs, respectively.
URI
http://pubs.kist.re.kr/handle/201004/37602
ISSN
0032-0943
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KIST Publication > Article
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