Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Screening of Chemosensitizer Candidates Using Natural Extracts

천연 추출물을 이용한 화학감작제 후보물질 탐색

  • Ahn, Hee-Jeong (Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine) ;
  • Kim, Ji-Young (Department of Biosciences and Biotechnology, IBST, Konkuk University) ;
  • Lee, Choong-Hwan (Department of Biosciences and Biotechnology, IBST, Konkuk University) ;
  • Song, Im-Sook (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)
  • 안희정 (인제대학교 의과대학 약리학교실 약물유전체연구센터) ;
  • 김지영 (건국대학교 생명공학과) ;
  • 이충환 (건국대학교 생명공학과) ;
  • 송임숙 (인제대학교 의과대학 약리학교실 약물유전체연구센터) ;
  • 유광현 (인제대학교 의과대학 약리학교실 약물유전체연구센터)
  • Published : 2008.09.30
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Abstract

P-glycoprotein (P-gp) is a very important drug transporter, which plays an important role in drug disposition and represents an additional mechanism for the development of multidrug resistance. Flavonoids, a major class of natural compounds widely present in foods and herbal products, have been shown to be P-gp inhibitors. The objective of the present study was to identify new chemosensitizer candidates through the screening of various herbal extracts. The inhibitory effects of herbal extracts on P-gp activity were assessed by measuring accumulation of calcein AM using P-gp overexpressed L-MDR1 cells. Curcuma longa showed the most potent inhibition on P-gp function. The inhibitory potential of P-gp was in the order: Curcuma longa > Curcuma aromatica > Ageratum conizoids > Zanthoxylum planispinum > Zedoariae rhizome > Rakta chandan > Dalbergia odorifera > Caesalpinia Sappan > Aloe ferox. To identify individual constituents with inhibitory activity, the herbal extracts were analyzed by LC/MS/MS. Several flavonoids such as curcumin, a well-known P-gp inhibitor, were identified through mass spectral library search. These in vitro data indicate that herbal extracts contain constituents that can potently inhibit the activities of P-gp and suggest that these herbal extracts should be examined for potential chemosensitizer in vivo.

본 연구에서는 다양한 천연 추출물의 P-gp 저해능의 고속 탐색을 통하여 새로운 화학감작제 후보물질을 발굴하고자 하였다. P-gp 활성에 대한 천연 추출물의 저해능은 P-gp이 과발현된 L-MDR1 세포주를 이용하여 대표적인 P-gp 기질 약물인 calcein AM의 세포 내 축적 정도를 측정함으로써 평가하였다. 강황 및 울금은 가장 강력한 P-gp 기능 저해를 나타내었고, 이외에도 Mentrasto, 취호초, 봉출, Rakta chandan, 강진향, 소목, 노회 등의 순으로 P-gp 기능 저해능을 보였다. 이들 추출물에서 P-gp 저해능을 보이는 성분을 확인하기 위하여 LC/MS/MS 분석을 수행한 결과, 기존에 P-gp 활성을 저해한다고 잘 알려진 curcumin 이외에, 다양한 플라보노이드 화합물이 질량 스펙트럼 DB 검색을 통하여 확인되었다. In vitro 연구 결과를 통하여 상기의 천연 추출물이 P-gp 활성을 저해하는 성분을 함유하고 있음을 확인하였다. 향후 이들 천연 추출물의 화학감작제 후보물질로의 사용 가능성에 대한 in vivo 연구가 필요할 것이다.

Keywords

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