Wang Qun, Sun Albert Y, Simonyi Agnes, Jensen Michael D, Shelat Phullara B, Rottinghaus George E, MacDonald Ruth S, Miller Dennis K, Lubahn Dennis E, Weisman Gary A, Sun Grace Y
Department of Biochemistry, University of Missouri, Columbia, Missouri 65212, USA.
J Neurosci Res. 2005 Oct 1;82(1):138-48. doi: 10.1002/jnr.20610.
Increased oxidative stress has been regarded as an important underlying cause for neuronal damage induced by cerebral ischemia/reperfusion (I/R) injury. In recent years, there has been increasing interest in investigating polyphenols from botanical source for possible neuroprotective effects against neurodegenerative diseases. In this study, we investigated the mechanisms underlying the neuroprotective effects of curcumin, a potent polyphenol antioxidant enriched in tumeric. Global cerebral ischemia was induced in Mongolian gerbils by transient occlusion of the common carotid arteries. Histochemical analysis indicated extensive neuronal death together with increased reactive astrocytes and microglial cells in the hippocampal CA1 area at 4 days after I/R. These ischemic changes were preceded by a rapid increase in lipid peroxidation and followed by decrease in mitochondrial membrane potential, increased cytochrome c release, and subsequently caspase-3 activation and apoptosis. Administration of curcumin by i.p. injections (30 mg/kg body wt) or by supplementation to the AIN76 diet (2.0 g/kg diet) for 2 months significantly attenuated ischemia-induced neuronal death as well as glial activation. Curcumin administration also decreased lipid peroxidation, mitochondrial dysfunction, and the apoptotic indices. The biochemical changes resulting from curcumin also correlated well with its ability to ameliorate the changes in locomotor activity induced by I/R. Bioavailability study indicated a rapid increase in curcumin in plasma and brain within 1 hr after treatment. Together, these findings attribute the neuroprotective effect of curcumin against I/R-induced neuronal damage to its antioxidant capacity in reducing oxidative stress and the signaling cascade leading to apoptotic cell death.
氧化应激增加被认为是脑缺血/再灌注（I/R）损伤诱导神经元损伤的一个重要潜在原因。近年来，人们越来越关注研究来自植物源的多酚对神经退行性疾病可能的神经保护作用。在本研究中，我们研究了姜黄素的神经保护作用机制，姜黄素是一种富含在姜黄中的强效多酚抗氧化剂。通过短暂阻断双侧颈总动脉在蒙古沙鼠中诱导全脑缺血。组织化学分析表明，在I/R后4天，海马CA1区出现广泛的神经元死亡，同时反应性星形胶质细胞和小胶质细胞增加。这些缺血性变化之前是脂质过氧化的快速增加，随后是线粒体膜电位降低、细胞色素c释放增加，随后是caspase-3激活和细胞凋亡。通过腹腔注射（30mg/kg体重）或在AIN76饮食中补充（2.0g/kg饮食）姜黄素2个月，可显著减轻缺血诱导的神经元死亡以及胶质细胞活化。给予姜黄素还可降低脂质过氧化、线粒体功能障碍和凋亡指数。姜黄素引起的生化变化也与其改善I/R诱导的运动活动变化的能力密切相关。生物利用度研究表明，治疗后1小时内血浆和脑中姜黄素迅速增加。总之，这些发现将姜黄素对I/R诱导的神经元损伤的神经保护作用归因于其抗氧化能力，即减少氧化应激以及导致凋亡细胞死亡的信号级联反应。
