Modulation of multiple pathways involved in the maintenance of neuronal function during aging by fisetin
Modulation of multiple pathways involved in the maintenance of neuronal function during aging by fisetin
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DOI：
10.1007/s12263-009-0142-5
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发表时间：
2009-12-01
影响因子：
3.5
通讯作者：
Maher, Pamela
中科院分区：
文献类型：
--
作者：
Maher, Pamela
与年龄相关的脑功能衰退涉及多种因素。因此，仅调节单一因素不太可能有效地减缓这种下降。一种更好的方法是识别具有与维持大脑功能相关的多种生物活动的小分子。在过去的几年里，我们已经确定了一种口服活性的，新型的神经保护和认知增强分子，类黄酮非塞酮。非瑟酮不仅具有直接的抗氧化活性，还能增加细胞内主要抗氧化剂谷胱甘肽的水平。非瑟酮还能在氧化应激下维持线粒体功能。此外，它对小胶质细胞具有抗炎活性，抑制5-脂氧合酶的活性，从而减少脂质过氧化物及其促炎副产物的产生。这种广泛的作用表明，非瑟酮有能力减少与年龄相关的脑功能衰退。
Multiple factors have been implicated in the age-related declines in brain function. Thus, it is unlikely that modulating only a single factor will be effective at slowing this decline. A better approach is to identify small molecules that have multiple biological activities relevant to the maintenance of brain function. Over the last few years, we have identified an orally active, novel neuroprotective and cognition-enhancing molecule, the flavonoid fisetin. Fisetin not only has direct antioxidant activity but it can also increase the intracellular levels of glutathione, the major intracellular antioxidant. Fisetin can also maintain mitochondrial function in the presence of oxidative stress. In addition, it has anti-inflammatory activity against microglial cells and inhibits the activity of 5-lipoxygenase, thereby reducing the production of lipid peroxides and their pro-inflammatory by-products. This wide range of actions suggests that fisetin has the ability to reduce the age-related decline in brain function.