Havermann Susannah, Humpf Hans-Ulrich, Wätjen Wim
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.
Westfälische Wilhelms-Universität Münster, Institute of Food Chemistry, Corrensstr. 45, 48149 Münster, Germany.
Fitoterapia. 2016 Sep;113:123-7. doi: 10.1016/j.fitote.2016.06.018. Epub 2016 Jun 28.
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.
黄酮类化合物黄芩素已被证明是哺乳动物细胞系中转录因子Nrf2的激活剂。我们发现它还能调节秀丽隐杆线虫中的Nrf2同源物SKN-1，并通过该途径对线虫产生有益影响：黄芩素增强了秀丽隐杆线虫对致死性热应激和亚砷酸钠应激的抵抗力，并剂量依赖性地延长了线虫的寿命。通过对SKN-1进行RNA干扰，我们能够证明寿命的延长和应激抵抗力的增强依赖于该转录因子。DAF-16（与哺乳动物FOXO同源）是线虫中另一个关键的衰老相关转录因子。我们证明DAF-16不参与黄芩素的有益作用：由于黄芩素不会导致DAF-16的核转位增加（表达DAF-16::GFP的菌株，孵育时间：1小时），并且即使在DAF-16功能缺失的菌株中它仍能诱导长寿，我们得出结论，黄芩素通过SKN-1而非DAF-16增加秀丽隐杆线虫的应激抵抗力和寿命。
