title: Baicalein modulates stress-resistance and life span in C. elegans via SKN-1 but not DAF-16.
abstract: The flavonoid baicalein has been demonstrated to be an activator of the transcription factor Nrf2 in mammalian cell lines. We show that it further modulates the Nrf2 homolog SKN-1 in Caenorhabditis elegans and by this pathway mediates beneficial effects in the nematode: baicalein enhances the resistance of C. elegans against lethal thermal and sodium arsenite stress and dose-dependently prolongs the life span of the nematode. Using RNA interference against SKN-1 we were able to show that the induction of longevity and the enhanced stress-resistance were dependent on this transcription factor. DAF-16 (homolog to mammalian FOXO) is another pivotal aging-related transcription factor in the nematode. We demonstrate that DAF-16 does not participate in the beneficial effects of baicalein: since baicalein causes no increase in the nuclear translocation of DAF-16 (DAF-16::GFP expressing strain, incubation time: 1h) and it still induces longevity even in a DAF-16 loss-of-function strain, we conclude, that baicalein increases stress-resistance and life span in C. elegans via SKN-1 but not DAF-16.
authors.affiliation: Martin-Luther-Universität Halle-Wittenberg, Institute of Agricultural and Nutritional Sciences, Weinbergweg 22, 06120 Halle/Saale, Germany; Westfälische Wilhelms-Universität Münster, Institute of Food Chemistry, Corrensstr. 45, 48149 Münster, Germany; Heinrich-Heine-Universität Düsseldorf, Institute of Toxicology, P.O. Box 101007, 40001 Düsseldorf, Germany.
authors.forename: Susannah
authors.initials: S
authors.lastname: Havermann
authors.affiliation: Westfälische Wilhelms-Universität Münster, Institute of Food Chemistry, Corrensstr. 45, 48149 Münster, Germany.
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Humpf
authors.affiliation: Martin-Luther-Universität Halle-Wittenberg, Institute of Agricultural and Nutritional Sciences, Weinbergweg 22, 06120 Halle/Saale, Germany; Heinrich-Heine-Universität Düsseldorf, Institute of Toxicology, P.O. Box 101007, 40001 Düsseldorf, Germany. Electronic address: wim.waetjen@landw.uni-halle.de.
authors.forename: Wim
authors.initials: W
authors.lastname: Wätjen
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D044950:Flavanones / Q000494:pharmacology*; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D008136:Longevity / Q000187:drug effects*; D034622:RNA Interference; D013312:Stress, Physiological; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D044950:Flavanones; D051858:Forkhead Transcription Factors; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C073702:skn-1 protein, C elegans; C006680:baicalein
keywords: Insulin-signaling; Nrf2; Oxidative stress; Secondary plant compounds; TCM