論文

基本情報

氏名 太田 千穂
氏名(カナ) オオタ チホ
氏名(英語) CHIHO OHTA
所属 中村学園大学 栄養科学部 栄養科学科
職名 准教授

題名

Comparative study on nobiletin metabolism with liver microsomes from rats, guinea pigs and hamsters and rat cytochrome P450

単著・共著の別

 

著者

Nobuyuki Koga
Miki Matsuo
Chiho Ohta
Koichi Haraguchi
Mikiko Matsuoka
Yoshihisa Kato
Toshinao Ishii
Masamichi Yano
Hideaki Ohta

担当区分

 

概要

In vitro metabolism of nobiletin, a polymethoxy-flavonoid abundantly present in citrus peels, was studied using liver microsomes of rats, hamsters and guinea pigs and ten cDNA-expressed rat cytochrome P450 (P450). The effects of P450 inducers on nobiletin metabolism were also investigated. Aerobical incubation with NADPH and animal liver microsomes transformed nobiletin to five metabolites, M-1, M-2, M-3, M-4 and M-5. From LC-MS and H-1-NMR data and a time-course study, these were assumed to be 4'-hydroxy (OH)-, 7-OH-, 6-OH-, 3',4'-diOH- and 6,7-diOH-metabolites, respectively. Pretreatment of animals with phenobarbital increased M-2 and M-3 to about 2-fold that in untreated animals. Pretreatment with 3-methylcholanthrene (MC) resulted in remarkable increases of both M-1 and M-4 (3 to 9-fold that of untreated). Males had 2-3 times higher M-2 and M-3 formation activities in rats, and for M-2 in hamsters than did females. Immunoinhibition study using antiserum against P450 revealed the involvement of hamster CYP1A2 in the formation of M-1 and M-4 in hamster liver. Of ten rat P450s, CYP2C11, CYP3A1, CYP3A2 and CYP2D1 had high activities for the formation of M-1, M-2 and M-3. Another P450s (CYP1A1, CYP2C12 and CYP1A2) also showed activity for the formation of M-1. Only CYP1A1 produced 3',4'-diOH-metabolites (M-4). However, CYP2A1, CYP2B1 and CYP2E1 had no activity for nobiletin. These results suggested that constitutive P450s such as CYP2C11, CYP2D1, CYP3A1, CYP3A2 and CYP2C12 are responsible for the demethylation at the 6-, 7-, 3'- and 4'-positions; whereas, MC-inducible P450s, CYP1A1 and CYP1A2, preferentially catalyzed demethylation at the 3'-and 4'-positions.

発表雑誌等の名称

Biol. Pharm. Bull

出版者

PHARMACEUTICAL SOC JAPAN

30

12

開始ページ

2317

終了ページ

2323

発行又は発表の年月

2007

査読の有無

無し

招待の有無

無し

記述言語

英語

掲載種別

研究論文(学術雑誌)

国際・国内誌

 

国際共著

 

ISSN

 

eISSN

 

DOI

10.1248/bpb.30.2317

Cinii Articles ID

 

Cinii Books ID

 

Pubmed ID

 

PubMed Central 記事ID

 

形式

無償ダウンロード

JGlobalID

 

arXiv ID

 

ORCIDのPut Code

 

DBLP ID