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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.
Eur J Nutr 2016; 55(1):257-65EJ

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.

Authors+Show Affiliations

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

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

25644181

Citation

Büchter, Christian, et al. "Isoxanthohumol, a Constituent of Hop (Humulus Lupulus L.), Increases Stress Resistance in Caenorhabditis Elegans Dependent On the Transcription Factor DAF-16." European Journal of Nutrition, vol. 55, no. 1, 2016, pp. 257-65.
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. 2016;55(1):257-65.
Büchter, C., Havermann, S., Koch, K., & Wätjen, W. (2016). Isoxanthohumol, a constituent of hop (Humulus lupulus L.), increases stress resistance in Caenorhabditis elegans dependent on the transcription factor DAF-16. European Journal of Nutrition, 55(1), pp. 257-65. doi:10.1007/s00394-015-0843-z.
Büchter C, 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. 2016;55(1):257-65. PubMed PMID: 25644181.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Isoxanthohumol, a constituent of hop (Humulus lupulus L.), increases stress resistance in Caenorhabditis elegans dependent on the transcription factor DAF-16. AU - Büchter,Christian, AU - Havermann,Susannah, AU - Koch,Karoline, AU - Wätjen,Wim, Y1 - 2015/02/03/ PY - 2014/09/10/received PY - 2015/01/25/accepted PY - 2015/2/4/entrez PY - 2015/2/4/pubmed PY - 2016/11/9/medline KW - Ageing KW - Beer KW - DAF-16 KW - Nutrition KW - Oxidative stress KW - Secondary plant compounds SP - 257 EP - 65 JF - European journal of nutrition JO - Eur J Nutr VL - 55 IS - 1 N2 - 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. SN - 1436-6215 UR - https://www.unboundmedicine.com/medline/citation/25644181/Isoxanthohumol_a_constituent_of_hop__Humulus_lupulus_L___increases_stress_resistance_in_Caenorhabditis_elegans_dependent_on_the_transcription_factor_DAF_16_ L2 - https://dx.doi.org/10.1007/s00394-015-0843-z DB - PRIME DP - Unbound Medicine ER -