Kampkötter Andreas, Nkwonkam Christiane Gombitang, Zurawski Ruben Felix, Timpel Claudia, Chovolou Yvonni, Wätjen Wim, Kahl Regine
Institute of Toxicology, Heinrich-Heine University, Düsseldorf, Germany.
Toxicology. 2007 May 5;234(1-2):113-23. doi: 10.1016/j.tox.2007.02.006. Epub 2007 Feb 21.
Oxidative stress as a result of excessive generation of reactive oxygen species (ROS) or diminished antioxidative defence is regarded as a main factor in the pathophysiology of various diseases and ageing. Many flavonoids that are present in herbal edibles have antioxidative properties and possess a remarkable spectrum of biochemical and pharmacological actions. They are assumed to exert beneficial effects but the precise biological mechanism of their action is unknown. In this project, we studied effects of the flavonoids quercetin and rutin in the multicellular model organism Caenorhabditis elegans that exhibits a strong conservation in molecular and cellular pathways to mammals. Both flavonoids reduced the ROS accumulation at thermal stress and the extent of induced oxidative stress with quercetin having a stronger impact. The higher antioxidative activity of quercetin may explain the protection against lethal thermal stress and the reduction in accumulation of the ageing marker lipofuscin exerted by quercetin but not by rutin. The subcellular distribution of the FoxO transcription factor DAF-16 was only affected by quercetin indicating a modulatory effect of quercetin on signalling cascade(s). These results suggest that quercetin may act as an antioxidant as well as a modulator of cellular signalling processes to exert its protective properties.
活性氧物种（ROS）过度生成或抗氧化防御能力减弱所导致的氧化应激，被视为多种疾病及衰老病理生理学中的一个主要因素。许多存在于可食用草本植物中的类黄酮具有抗氧化特性，并拥有一系列显著的生化及药理作用。它们被认为具有有益效果，但其确切的生物学作用机制尚不清楚。在本项目中，我们研究了类黄酮槲皮素和芦丁在多细胞模式生物秀丽隐杆线虫中的作用，该生物在分子和细胞途径方面与哺乳动物具有高度保守性。两种类黄酮都能减少热应激下的ROS积累以及诱导的氧化应激程度，其中槲皮素的影响更强。槲皮素较高的抗氧化活性可能解释了其对致死性热应激的保护作用以及槲皮素而非芦丁对衰老标志物脂褐素积累的减少作用。FoxO转录因子DAF-16的亚细胞分布仅受槲皮素影响，这表明槲皮素对信号级联反应具有调节作用。这些结果表明，槲皮素可能作为一种抗氧化剂以及细胞信号传导过程的调节剂来发挥其保护特性。
