Screening and Biotransformation of Interleukin-1$\beta$ Converting Enzyme Production Inhibitors from Arctii fructus

  • KIM HYUN A (Immune Modulator Research Laboratory, Korea Research Institute of Bioscience and Biotechnology) ;
  • YOON DO YOUNG (Immune Modulator Research Laboratory, Korea Research Institute of Bioscience and Biotechnology) ;
  • LEE SANG MYUNG (KT & G Central Research) ;
  • BAEK SEUNG HWA (Immune Modulator Research Laboratory, Korea Research Institute of Bioscience and Biotechnology) ;
  • HAN GYOON HEE (Immune Modulator Research Laboratory, Korea Research Institute of Bioscience and Biotechnology) ;
  • KHO YOUNG HEE (Immune Modulator Research Laboratory, Korea Research Institute of Bioscience and Biotechnology) ;
  • LEE CHOONG HWAN (Immune Modulator Research Laboratory, Korea Research Institute of Bioscience and Biotechnology)
  • Published : 2005.04.01

Abstract

Five dibenzylbutyrolactones were isolated from a methanol extract of Arctii fructus (Arctium lappa L.) by bioassay-guided isolation, using the interleukin-l $\beta$ converting enzyme (caspase-l, ICE) production inhibitory assay in vitro. These compounds were spectroscopically identified as lappaol E (1), lappaol A (2), matairesinol (3), arctigenin (4), and arctiin (5). Among the compounds tested, arctigenin (4) showed the strongest inhibitory activity for ICE production in IL-$\beta$-induced proliferation of D 1 OS cells. Western blot analysis demonstrated that the arctigenin suppressed the expression of ICE protein in a dose-dependent manner. To estimate the biotransformation of Arctii fructus in vivo by human intestinal bacteria, we carried out an anaerobic incubation of the Arctii fructus extract with a human fecal suspension. From the HPLC analysis of metabolites, Arctiin (IC$_{50}$=74.2$\mu$g/ml), a major component of Arctii fructus, was transformed to aglycone, arctigenin (IC$_{50}$=12.5$\mu$g/ml), by human intestinal bacteria. The ICE production inhibitory activity of Arctii fructus would be much stronger in vivo than in vitro due to the biotransformation by human intestinal bacteria.

Keywords

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