Effects of the flavonoids kaempferol and fisetin on thermotolerance, oxidative stress and FoxO transcription factor DAF-16 in the model organism Caenorhabditis elegans
Effects of the flavonoids kaempferol and fisetin on thermotolerance, oxidative stress and FoxO transcription factor DAF-16 in the model organism Caenorhabditis elegans
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DOI：
10.1007/s00204-007-0215-4
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发表时间：
2007-12-01
影响因子：
6.1
通讯作者：
Kahl, Regine
中科院分区：
文献类型：
--
作者：
Kampkoetter, Andreas;Nkwonkam, Christiane Gombitang;Kahl, Regine
存在于许多草药食品中的风味物质具有显著的生物化学和药理学作用，并且它们被认为对人类健康产生有益的影响。虽然其作用的精确生物学机制尚未阐明，但类黄酮的许多保护特性归因于其抗氧化活性，因为氧化应激被认为是各种疾病和衰老的病理生理学中的主要因素。氧化应激是由于活性氧（ROS）的过度产生或抗氧化防御的减少而引起的，因此抗氧化剂能够抵消这种情况。我们使用的多细胞模式生物秀丽隐杆线虫，是保守的分子和细胞途径的哺乳动物，研究黄酮类化合物山奈酚和非瑟酮的影响，他们的保护作用，在个别活蠕虫。两种黄酮类化合物均能提高C. elegans，减少细胞内ROS积累在致死热应激，并减少诱导的氧化应激的程度与山奈酚具有更强的影响。山奈酚而非非漆黄素减弱了衰老标志物脂褐素的积累，表明这种类黄酮具有延长寿命的活性。除了这些可能归因于其抗氧化潜力的作用外，山奈酚和非瑟酮还引起了C。elegans FoxO转录因子16从细胞质到细胞核的变化表明两种黄酮类化合物对信号级联的调节作用。
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).