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Planta Med 2010; 76(7): 701-704
DOI: 10.1055/s-0029-1240657
Pharmacology
Letters
© Georg Thieme Verlag KG Stuttgart · New York

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

Sang Kyu Lee1 , Yoon Kim1 , Changbae Jin1 , Seung Ho Lee2 , Mi Jeong Kang2 , Tae Cheon Jeong2 , Seo Young Jeong3 , Dong-Hyun Kim4 , Hye Hyun Yoo1
  • 1Doping Control Center, Korea Institute of Science and Technology, Chungryang, Seoul, Korea
  • 2College of Pharmacy, Yeungnam University, Dae-dong, Gyeongsan, Korea
  • 3College of Pharmacy, Kyung-Hee University, Seoul, Korea
  • 4Research Center, Yuyu Pharma, Inc., Suwon-city, Gyeonggi-do, Korea
Further Information

Publication History

received September 9, 2009 revised October 25, 2009

accepted November 2, 2009

Publication Date:
03 December 2009 (online)

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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 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, DPT was characterized to be a competitive inhibitor of CYP2C9 and CYP3A4, with K i 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.

Key words

deoxypodophyllotoxin - cytochrome P450 - competitive inhibition - cocktail probe assay - Anthriscus sylvestris - Apiaceae

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Ph.D. Hye Hyun Yoo

Doping Control Center
Korea Institute of Science and Technology

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