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DOI: 10.1055/s-2004-827207
© Georg Thieme Verlag KG Stuttgart · New York
Induction of Cytochrome P450s by Rutaecarpine and Metabolism of Rutaecarpine by Cytochrome P450s
Publikationsverlauf
Received: December 29, 2003
Accepted: April 24, 2004
Publikationsdatum:
24. August 2004 (online)
![](https://www.thieme-connect.de/media/plantamedica/200408/lookinside/thumbnails/10.1055-s-2004-827207-1.jpg)
Abstract
Rutaecarpine is an alkaloid originally isolated from the unripe fruit of Evodia rutaecarpa. Recently, rutaecarpine has been characterized to have an anti-inflammatory activity through cyclooxygenase-2 inhibition. In the present studies, the effects of rutaecarpine on liver cytochrome P450 s (P450s) and P450 s involved in the metabolism of rutaecarpine were studied in vivo and in vitro, respectively, because the data are crucial in the early development of rutaecarpine as a new drug candidate. Oral administration to male ICR mice of rutaecarpine for 3 consecutive days induced liver P450 1A-, 2B- and 2E1-selective monooxygenase activities. The induction of P450 1A and 2B by rutaecarpine was confirmed by Western immunoblotting. When rutaecarpine was incubated with rat liver microsomes in the presence of an NADPH-generating system, five metabolites were detected by UV and mass spectral analyses. The 3-methylcholanthrene- and phenobarbital-induced microsomes greatly increased the formation of metabolites. Our present results suggest that rutaecarpine might induce P450 1A and 2B in mice, and that P450 1A and 2B might predominantly metabolize rutaecarpine in rat liver microsomes.
Key words
Rutaecarpine - Evodia rutaecarpa - Rutaceae - induction - cytochrome P450s - metabolism - liver microsomes - metabolites
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Tae Cheon Jeong, Ph. D.
College of Pharmacy
Yeungnam University
214-1 Dae-dong
Kyungsan 712-749
Korea
Telefon: +82-53-810-2819
Fax: +82-53-810-4654
eMail: taecheon@yumail.ac.kr