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Isoxanthohumol, a constituent of hop (Humulus lupulus L.), increases stress resistance in Caenorhabditis elegans dependent on the transcription factor DAF-16

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Abstract

Purpose

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.

Conclusion

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.

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Acknowledgments

We thank Dr. Sebastian Honnen (Heinrich-Heine-University, Düsseldorf) for critical comments. The nematode strains used in this work were provided by the Caenorhabditis Genetics Centre, which is funded by the NIH National Centre for Research Resources (NCRR). We thank Dr. Gerd Hause (Biozentrum, Halle) and Prof. Dr. Bettina Hause (IPB, Halle) for being able to use the fluorescence microscope.

Conflict of interest

The authors declare that there is no conflict of interests regarding the publication of this manuscript.

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Authors and Affiliations

  1. Biofunctionality of Secondary Plant Compounds, Institute of Agricultural and Nutritional Sciences, Martin-Luther-Universität Halle-Wittenberg, Weinbergweg 22 (Biozentrum), 06120, Halle/Saale, Germany

    Christian Büchter, Susannah Havermann, Karoline Koch & Wim Wätjen

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  1. Christian Büchter
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  2. Susannah Havermann
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  4. Wim Wätjen
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Correspondence to Wim Wätjen.

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Büchter, C., Havermann, S., Koch, K. et al. Isoxanthohumol, a constituent of hop (Humulus lupulus L.), increases stress resistance in Caenorhabditis elegans dependent on the transcription factor DAF-16. Eur J Nutr 55, 257–265 (2016). https://doi.org/10.1007/s00394-015-0843-z

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