title: Isoxanthohumol, a constituent of hop (Humulus lupulus L.), increases stress resistance in Caenorhabditis elegans dependent on the transcription factor DAF-16.
abstract: OBJECTIVE
  The flavanone isoxanthohumol (IX) has gained attention as antioxidative and chemopreventive agent, but the molecular mechanism of action remains unclear. We investigated effects of this secondary plant compound in vivo using the model organism Caenorhabditis elegans.
  
  
  METHODS
  Adult C. elegans nematodes were incubated with IX, and then, the stress resistance was analysed in the SYTOX assay; lifespan was monitored by touch-provoked movement method, the amount of reactive oxygen species (ROS) was measured in the DCF assay, and the nuclear localisation of the transcription factor DAF-16 was analysed by using a transgenic strain. By the use of a DAF-16 loss-of-function strain, we analysed whether the effects are dependent on DAF-16.
  
  
  RESULTS
  IX increases the resistance of the nematode against thermal stress. Additionally, a reduction in ROS in vivo was caused by IX. Since the flavanone only has a marginal radical-scavenging capacity (TEAC assay), we suggest that IX mediates its antioxidative effects indirectly via activation of DAF-16 (homologue to mammalian FOXO proteins). The nuclear translocation of this transcription factor is increased by IX. In the DAF-16-mutated strain, the IX-mediated increase in stress resistance was completely abolished; furthermore, an increased formation of ROS and a reduced lifespan was mediated by IX.
  
  
  CONCLUSIONS
  IX or a bacterial metabolite of IX causes antioxidative effects as well as an increased stress resistance in C. elegans via activation of DAF-16. The homologous pathway may have implications in the molecular mechanism of IX in mammals.
authors: Biofunctionality of Secondary Plant Compounds, Institute of Agricultural and Nutritional Sciences, Martin-Luther-Universität Halle-Wittenberg, Weinbergweg 22 (Biozentrum), 06120, Halle/Saale, Germany.
authors: Christian
authors: C
authors: Büchter
authors: Biofunctionality of Secondary Plant Compounds, Institute of Agricultural and Nutritional Sciences, Martin-Luther-Universität Halle-Wittenberg, Weinbergweg 22 (Biozentrum), 06120, Halle/Saale, Germany.
authors: Susannah
authors: S
authors: Havermann
authors: Biofunctionality of Secondary Plant Compounds, Institute of Agricultural and Nutritional Sciences, Martin-Luther-Universität Halle-Wittenberg, Weinbergweg 22 (Biozentrum), 06120, Halle/Saale, Germany.
authors: Karoline
authors: K
authors: Koch
authors: Biofunctionality of Secondary Plant Compounds, Institute of Agricultural and Nutritional Sciences, Martin-Luther-Universität Halle-Wittenberg, Weinbergweg 22 (Biozentrum), 06120, Halle/Saale, Germany. wim.waetjen@landw.uni-halle.de.
authors: Wim
authors: W
authors: Wätjen
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017173:Caenorhabditis elegans / Q000187:drug effects*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D044950:Flavanones / Q000494:pharmacology; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D027582:Humulus / Q000737:chemistry*; D008136:Longevity / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D044004:Xanthones / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D029742:Caenorhabditis elegans Proteins; D044950:Flavanones; D051858:Forkhead Transcription Factors; D017382:Reactive Oxygen Species; D044004:Xanthones; C108831:daf-16 protein, C elegans; C512910:isoxanthohumol; C028610:flavanone
keywords: Ageing; Beer; DAF-16; Nutrition; Oxidative stress; Secondary plant compounds
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