The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse
The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse
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DOI：
10.1523/jneurosci.21-21-08370.2001
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发表时间：
2001-11-01
影响因子：
5.3
通讯作者：
Cole, GM
中科院分区：
文献类型：
--
作者：
Lim, GP;Chu, T;Cole, GM
阿尔茨海默病（AD）患者的炎症特征是细胞因子增加和小胶质细胞活化。流行病学研究表明，AD风险降低与长期使用非甾体抗炎药（NSAID）有关。在阿尔茨海默病转基因APPSw小鼠模型（Tg 2576）中，慢性布洛芬抑制炎症和斑块相关病理学，而过度使用靶向环氧化酶I的NSAID可导致胃肠道、肝脏和肾脏毒性。另一种非甾体抗炎药是姜黄素，来源于咖喱香料姜黄。姜黄素在印度作为食品添加剂和草药有着悠久的历史，也是一种有效的多酚抗氧化剂。为了评估它是否会影响APPSw小鼠中的阿尔茨海默病样病理学，我们测试了低剂量（160 ppm）和高剂量（5000 ppm）的饮食姜黄素对炎症，氧化损伤和斑块病理学的影响。低剂量和高剂量的姜黄素显著降低了氧化蛋白和白细胞介素-1 β，这是一种在这些小鼠大脑中升高的促炎细胞因子。用低剂量但不是高剂量姜黄素治疗，星形胶质细胞标志物GFAP减少，并且不溶性β-淀粉样蛋白（A β）、可溶性A β和斑块负荷显著降低43- 50%。然而，淀粉样蛋白前体（APP）在膜部分的水平没有减少。小胶质细胞增生也被抑制在神经元层，但不邻近斑块。鉴于其功效和明显的低毒性，这种印度香料成分显示出预防阿尔茨海默病的希望。
Inflammation in Alzheimer's disease (AD) patients is characterized by increased cytokines and activated microglia. Epidemiological studies suggest reduced AD risk associates with long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs). Whereas chronic ibuprofen suppressed inflammation and plaque-related pathology in an Alzheimer transgenic APPSw mouse model (Tg2576), excessive use of NSAIDs targeting cyclooxygenase I can cause gastrointestinal, liver, and renal toxicity. One alternative NSAID is curcumin, derived from the curry spice turmeric. Curcumin has an extensive history as a food additive and herbal medicine in India and is also a potent polyphenolic antioxidant. To evaluate whether it could affect Alzheimer-like pathology in the APPSw mice, we tested a low (160 ppm) and a high dose of dietary curcumin (5000 ppm) on inflammation, oxidative damage, and plaque pathology. Low and high doses of curcumin significantly lowered oxidized proteins and interleukin-1 beta, a proinflammatory cytokine elevated in the brains of these mice. With low-dose but not high-dose curcumin treatment, the astrocytic marker GFAP was reduced, and insoluble beta -amyloid (A beta), soluble A beta, and plaque burden were significantly decreased by 43-50%. However, levels of amyloid precursor (APP) in the membrane fraction were not reduced. Microgliosis was also suppressed in neuronal layers but not adjacent to plaques. In view of its efficacy and apparent low toxicity, this Indian spice component shows promise for the prevention of Alzheimer's disease.