Effects of the flavonoids kaempferol and fisetin on thermotolerance, oxidative stress and FoxO transcription factor DAF-16 in the model organism Caenorhabditis elegans

Arch Toxicol. 2007 Dec;81(12):849-58. doi: 10.1007/s00204-007-0215-4. Epub 2007 Jun 6.

Abstract

Flavonoids present in many herbal edibles possess a remarkable spectrum of biochemical and pharmacological actions and they are assumed to exert beneficial effects to human health. Although the precise biological mechanisms of their action has not been elucidated yet many of the protective properties of flavonoids are attributed to their antioxidative activity since oxidative stress is regarded as a main factor in the pathophysiology of various diseases and ageing. Oxidative stress results from excessive generation of reactive oxygen species (ROS) or diminished antioxidative defence and thus antioxidants are able to counteract such situations. We used the multicellular model organism Caenorhabditis elegans that is conserved in molecular and cellular pathways to mammals to examine the effects of the flavonoids kaempferol and fisetin with respect to their protective action in individual living worms. Both flavonoids increased the survival of C. elegans, reduced the intracellular ROS accumulation at lethal thermal stress, and diminished the extent of induced oxidative stress with kaempferol having a stronger impact. Kaempferol but not fisetin attenuated the accumulation of the ageing marker lipofuscin suggesting a life prolonging activity of this flavonoid. In addition to these effects that may be attributed to their antioxidative potential kaempferol and fisetin caused a translocation of the C. elegans FoxO transcription factor DAF-16 from the cytosol to the nucleus indicating a modulatory influence of both flavonoids on signalling cascade(s).

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptation, Physiological / drug effects*
  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans / drug effects*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Flavonoids / chemistry
  • Flavonoids / pharmacology*
  • Fluoresceins / metabolism
  • Forkhead Transcription Factors
  • Glutathione Transferase / genetics
  • Glutathione Transferase / metabolism
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Hot Temperature
  • Kaempferols / chemistry
  • Kaempferols / pharmacology*
  • Lipofuscin / metabolism
  • Microscopy, Fluorescence
  • Molecular Structure
  • Naphthoquinones / pharmacology
  • Oxidative Stress / drug effects*
  • Reactive Oxygen Species / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction / drug effects
  • Time Factors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • 2',7'-dichlorodihydrofluorescein diacetate
  • Caenorhabditis elegans Proteins
  • Flavonoids
  • Fluoresceins
  • Forkhead Transcription Factors
  • Kaempferols
  • Lipofuscin
  • Naphthoquinones
  • Reactive Oxygen Species
  • Recombinant Fusion Proteins
  • Transcription Factors
  • daf-16 protein, C elegans
  • Green Fluorescent Proteins
  • Glutathione Transferase
  • fisetin
  • juglone