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
Author(s)
이상규[이상규]김윤[김윤]진창배[진창배]강미정정태천정서영[정서영]김동현[김동현]유혜현[유혜현]이승호
Keywords
CYTOCHROME-P450 3A4; METHYLENEDIOXYPHENYL LIGNANS; MASS-SPECTROMETRY; COMPLEX-FORMATION; LIVER-MICROSOMES; PROBE; BIOCONVERSION; CELLS; RAT
Issue Date
201005
Publisher
GEORG THIEME VERLAG KG
Citation
PLANTA MEDICA, v.76, no.7, pp.701 - 704
Abstract
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 mu M, 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 Ki values of 3.5 and 10.8 mu M in HLM and 24.9 and 3.5 mu M in baculovirus-insect cell-expressed human CYPs, respectively.
URI
http://hdl.handle.net/YU.REPOSITORY/22486http://dx.doi.org/10.1055/s-0029-1240657
ISSN
0032-0943
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약학대학 > 약학부 > Articles
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