Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Screening for inhibitory effect on nine CYP isoforms by 20 herbal medications

고속 스크리닝 기법을 이용한 한약제제의 cytochrome P45O 저해능 탐색

  • Kim, Hyun-Mi (Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine) ;
  • Liu, Kwang-Hyeon (Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine)
  • 김현미 (인제대학교 의과대학 약리학교실, 약물유전체연구센터) ;
  • 유광현 (인제대학교 의과대학 약리학교실, 약물유전체연구센터)
  • Published : 2007.03.30
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Abstract

We evaluated the potential of 20 herbal medications (HMs), commonly used in Korea, to inhibit the catalytic activities of several cytochrome P450 (CYP) isoforms. The abilities of 500 ${\mu}g/ml$ of aqueous extracts of 20 HMs to inhibit phenacetin O-deethylation (CYP1A2), coumarin 6-hydroxylation (CYP2A6), bupropion hydroxylation (CYP2B6), rosiglitazone hydroxylation (CYP2C8), tolbutamide 4-methylhydroxylation (CYP2C9), S-mephenytoin 4'-hydroxylation (CYP2C19), dextromethorphan O-demethylation (CYP2D6), chlorzoxazone 6-hydroxylation (CYP2E1), and midazolam 1'-hydroxylation (CYP3A) were tested using human liver microsomes. The HMs Woohwangcheongsimwon suspension and Hwanglyeonhaedok-Tang strongly inhibited CYP2B6 and CYP2D6 isoform activity, respectively. These results suggest that some of the HMs used in Korea have potential to inhibit CYP isoforms in vitro. Although the plasma concentrations of the active constituents of the HMs were not determined, some herbs could cause clinically significant interactions because the usual doses of those individual herbs are several grams of freeze-dried extracts.

본 연구는 우황청심원을 비롯한 상용되는 20종의 한약제제를 대상으로 9종의 시토크롬 동종효소에 대한 대사능의 저해정도를 고속 스크리닝 기법을 이용하여 탐색함으로써, 한약제제와 약물의 병용으로 인한 약물 상호작용 가능성을 평가하고자 하였다. 인체 간 마이크로좀 시료에 9종의 주요 시토크롬 약물대사효소의 지표약물과NADPH-generating system및 한약제제(500 ${\mu}g/ml$)를 첨가한 후 $37^{\circ}C$에서 15분간 반응시켜 생성된 각각의 대사물을 LC/MS/MS를 이용하여 정량하여 시토크롬 동종효소 활성의 변화를 평가하였다. 그 결과 우황청심원 현탁액 및 황련해독탕 물 추출물이 각각 CYP2B6 및 CYP2D6 효소 활성을 선택적으로 강력하게 저해하였다. 이러한 결과는 약국에서 쉽게 구입할 수 있는 한약제제들 중 일부는 인체 간 시토크롬 활성 저해능을 가지고 있고, 이들 효소에 의해 대사되는 약물과의 병용 복용시 약물상호작용 발생 가능성이 있음을 의미한다. 향후 한약제제에서 저해능을 나타내는 주된 성분을 규명하여 이 성분의 저해능과 저해 기전을 살피는 노력이 필요할 것이다.

Keywords

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