Fish oil enhances anti-amyloidogenic properties of green tea EGCG in Tg2576 mice
Fish oil enhances anti-amyloidogenic properties of green tea EGCG in Tg2576 mice
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DOI：
10.1016/j.neulet.2010.01.026
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发表时间：
2010-03-08
影响因子：
2.5
通讯作者：
Tan, Jun
中科院分区：
文献类型：
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作者：
Giunta, Brian;Hou, Houyan;Tan, Jun
β-淀粉样蛋白（A β）肽的细胞外斑块与阿尔茨海默病（AD）发病机制有关。α-分泌酶阻止β形成，α-分泌酶在APP的A β结构域内裂解，产生可溶性APP-α（sAPP-α）。因此，α-分泌酶上调可能是AD治疗的靶点。我们先前显示绿色茶衍生的EGCG增加AD小鼠模型中的sAPP-α。然而，人体中相当的EGCG有效剂量可能超过临床便利性和/或安全性。流行病学研究表明，食用鱼油与降低痴呆症风险有关。在这里，我们研究了鱼油（8 mg/kg/天）和EGCG（62.5 mg/kg/天或12.5 mg/kg/天）的口服联合治疗是否会减少Tg 2576小鼠中的AD样病理学。与单独使用任一种化合物相比，用鱼油和EGCG体外共处理N2 a细胞增强了sAPP-α的产生（P < 0.001）。鱼油可提高EGCG的生物利用度（P < 0.001）。鱼油和表没食子儿茶素没食子酸酯（EGCG）对脑A β沉积的抑制具有协同作用（P < 0.001），表明适量补充表没食子酸酯（EGCG）和鱼油对治疗AD具有显著的治疗潜力。(C)2010爱思唯尔爱尔兰有限公司版权所有。
Extracellular plaques of beta-amyloid (A beta) peptides are implicated in Alzheimer's Disease (AD) pathogenesis. A beta formation is precluded by alpha-secretase, which cleaves within the A beta domain of APP generating soluble APP-alpha (sAPP-alpha). Thus, alpha-secretase upregulation may be a target AD therapy. We previously showed green tea derived EGCG increased sAPP-alpha in AD mouse models. However, the comparable effective dose of EGCG in humans may exceed clinical convenience and/or safety. Epidemiological studies suggested fish oil consumption is associated with reduced dementia risk. Here we investigated whether oral co-treatment with fish oil (8 mg/kg/day) and EGCG (62.5 mg/kg/day or 12.5 mg/kg/day) would reduce AD-like pathology in Tg2576 mice. In vitro co-treatment of N2a cells with fish oil and EGCG enhanced sAPP-alpha production compared to either compound alone (P < 0.001). Fish oil enhanced bioavailability of EGCG versus EGCG treatment alone (P < 0.001). Fish oil and EGCG had a synergetic effect on inhibition of cerebral A beta deposits (P < 0.001) suggesting moderate supplementation with EGCG and fish oil having significant therapeutic potential for the treatment of AD. (C) 2010 Elsevier Ireland Ltd. All rights reserved.