Dietary flavonoids are neuroprotective through Nrf2-coordinated induction of endogenous cytoprotective proteins.
Dietary flavonoids are neuroprotective through Nrf2-coordinated induction of endogenous cytoprotective proteins.
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DOI：
10.1179/1476830511y.0000000013
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发表时间：
2011-09
影响因子：
3.6
通讯作者：
Doré S
中科院分区：
文献类型：
--
作者：
Leonardo CC;Doré S
流行病学研究表明，食用水果和蔬菜可降低心血管疾病和中风的风险。对这些食物的特定膳食成分的详细研究表明，许多多酚成分对参与缺血性损伤发病机制和进展的关键底物发挥抗氧化作用。这些数据使人们相信，黄酮类化合物的保护作用是由脑血管系统和脑实质水平的直接抗氧化作用引起的。虽然许多使用纯化提取物的体外研究支持这一观点，但首过代谢改变了类黄酮的生物利用度，使得口服后可达到的浓度与该机制不一致。重要的是，口服黄酮类化合物可以通过促进负责通过抗氧化和抗炎作用解毒缺血微环境的基因产物的表达来促进神经保护。特别是，转录因子核因子红细胞 2 相关因子 2 通过诱导各种细胞保护基因，已成为类黄酮介导的保护的关键调节因子。与有效转录调节相关的多效性可能代表了神经保护的主要机制，因为到达体内缺血组织的类黄酮浓度足以改变细胞内信号转导，但可能排除通过直接抗氧化提供保护所需的一对一化学计量。这些数据反映了补充和替代医学研究中令人兴奋的新方向，可能会导致缺血性/出血性中风、创伤性脑损伤和其他神经系统疾病的新疗法的开发。
Epidemiological studies have demonstrated that the consumption of fruits and vegetables is associated with reduced risk for cardiovascular disease and stroke. Detailed investigations into the specific dietary components of these foods have revealed that many polyphenolic constituents exert anti-oxidant effects on key substrates involved in the pathogenesis and progression of ischemic injury. These data have perpetuated the belief that the protective effects of flavonoids result from direct anti-oxidant actions at the levels of the cerebral vasculature and brain parenchyma. While many in vitro studies using purified extracts support this contention, first-pass metabolism alters the bioavailability of flavonoids such that the achievable concentrations after oral consumption are not consistent with this mechanism. Importantly, oral consumption of flavonoids may promote neural protection by facilitating the expression of gene products responsible for detoxifying the ischemic microenvironment through both anti-oxidative and anti-inflammatory actions. In particular, the transcriptional factor nuclear factor erythroid 2-related factor 2 has emerged as a critical regulator of flavonoid-mediated protection through the induction of various cytoprotective genes. The pleiotropic effects associated with potent transcriptional regulation likely represent the primary mechanisms of neural protection, as the flavonoid concentrations reaching ischemic tissues in vivo are sufficient to alter intracellular signal transduction but likely preclude the one-to-one stoichiometry necessary to confer protection by direct anti-oxidation. These data reflect an exciting new direction in the study of complementary and alternative medicine that may lead to the development of novel therapies for ischemic/hemorrhagic stroke, traumatic brain injury, and other neurological disorders.