title: Knockdown of the NHR-8 nuclear receptor enhanced sensitivity to the lipid-reducing activity of alkaloids in Caenorhabditis elegans.
abstract: Caenorhabditis elegans is a versatile, whole-organism model for bioactivity screening. However, this worm has extensive defensive mechanisms against xenobiotics which limit its use for screening of pharmacologically active compounds. In this study, we report that knockdown of nhr-8, a gene involved in the xenobiotic response, increased the worm's sensitivity to the lipid-reducing effects of some isoquinoline alkaloids, especially berberine. On the other hand, crude extract of rhizome and cultured cells showed enhanced biological activity compared to the pure alkaloids in wild type worm, but this enhanced activity was not detected in nhr-8 RNAi worm, suggesting that some components in cell extracts might interfere with the defense response in this worm. The possibility of using C. elegans as a model for screening bioactive chemicals is discussed.
authors: a Department of Plant Gene and Totipotency , Graduate School of Biostudies, Kyoto University , Kyoto , Japan.
authors: Yit-Lai
authors: YL
authors: Chow
authors: Yuriko
authors: Y
authors: Kawasaki
authors: Fumihiko
authors: F
authors: Sato
mesh_terms: D000818:Animals; D053119:Benzophenanthridines / Q000494:pharmacology*; D001599:Berberine / Q000494:pharmacology*; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D039323:Coptis / Q000737:chemistry*; D005786:Gene Expression Regulation; D057166:High-Throughput Screening Assays; D008658:Inactivation, Metabolic / Q000235:genetics; D007546:Isoquinolines / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D027343:Rhizome / Q000737:chemistry; D015398:Signal Transduction
chemical_list: D053119:Benzophenanthridines; D001599:Berberine; D029742:Caenorhabditis elegans Proteins; D007546:Isoquinolines; D010936:Plant Extracts; D034741:RNA, Small Interfering; D018160:Receptors, Cytoplasmic and Nuclear; C439299:nhr-8 protein, C elegans; C005705:sanguinarine
keywords: Caenorhabditis elegans; bioactivity screening; detoxification response; isoquinoline alkaloid; nuclear hormone receptor-8 (NHR-8)