A comparative study of curcuminoids to measure their effect on inflammatory and apoptotic gene expression in an Aβ plus ibotenic acid-infused rat model of Alzheimer's disease
A comparative study of curcuminoids to measure their effect on inflammatory and apoptotic gene expression in an Aβ plus ibotenic acid-infused rat model of Alzheimer's disease
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DOI：
10.1016/j.brainres.2011.05.022
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发表时间：
2011-07-11
期刊：
影响因子：
2.9
通讯作者：
Gilani, Anwarul-Hassan
中科院分区：
文献类型：
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作者：
Ahmed, Touqeer;Gilani, Anwarul-Hassan
阿尔茨海默病（AD）是一种神经退行性疾病，其特征表现为慢性炎症状态，导致细胞死亡，且治疗选择有限。我们旨在利用注射Aβ + 鹅膏蕈氨酸的大鼠模型，探究姜黄素类混合物及其单个成分对阿尔茨海默病中炎症和凋亡基因表达的影响。用去甲氧基姜黄素治疗5天后，与淀粉样蛋白处理组（373.99 ± 15.28%）相比，海马体中白细胞介素 - 1β水平在30mg/kg和10mg/kg剂量下分别降至118.54 ± 47.48和136.67 ± 31.96%。治疗5天后，姜黄素类混合物和去甲氧基姜黄素有效降低了海马体中的胶质纤维酸性蛋白水平。在研究它们对凋亡基因表达的影响时，姜黄素类混合物和双去甲氧基姜黄素在治疗20天后有效降低了海马体中的半胱天冬酶 - 3水平，其中双去甲氧基姜黄素在3mg/kg剂量下显示出最大的挽救作用（92.35 ± 3.07%）。姜黄素类混合物在30mg/kg剂量下，治疗5天后将海马体中FasL水平降至70.56 ± 3.36%，治疗20天后降至19.01 ± 2.03%。对于Fas受体水平，去甲氧基姜黄素在治疗5天后降低了其水平，三个剂量均有效果，在10mg/kg剂量下效果最大（189.76 ± 15.01%）。每种化合物在治疗20天后都能有效降低海马体中的Fas受体水平。这项研究揭示了姜黄素类物质对基因表达的重要影响，表明姜黄素类混合物的每种成分对基因表达都有明显影响，从而凸显了姜黄素类物质在阿尔茨海默病中的治疗潜力。（C）2011爱思唯尔公司。保留所有权利。
Alzheimer's disease (AD) is a neurodegenerative disorder, which depicts features of chronic inflammatory conditions resulting in cellular death and has limited therapeutic options. We aimed to explore the effect of a curcuminoid mixture and its individual components on inflammatory and apoptotic genes expression in AD using an A beta + ibotenic acid-infused rat model. After 5 days of treatment with demethoxycurcumin, hippocampal IL-1 beta levels were decreased to 118.54 +/- 47.48 and 136.67 +/- 31.96% respectively at 30 and 10 mg/kg, compared with the amyloid treated group (373.99 +/- 15.28%). After 5 days of treatment, the curcuminoid mixture and demethoxycurcumin effectively decreased GFAP levels in the hippocampus. When studied for their effect on apoptotic genes expression, the curcuminoid mixture and bisdemethoxycurcumin effectively decreased caspase-3 level in the hippocampus after 20 days of treatment, where bisdemethoxycurcumin showed a maximal rescuing effect (92.35 +/- 3.07%) at 3 mg/kg. The curcuminoid mixture at 30 mg/kg decreased hippocampal FasL level to 70.56 +/- 3.36% after 5 days of treatment and 19.01 +/- 2.03% after 20 days. In the case of Fas receptor levels, demethoxycurcumin decreased levels after 5 days of treatment with all three doses showing a maximal effect (189.76 +/- 15.01%) at 10 mg/kg. Each compound was effective after 20 days in reducing Fas receptor levels in the hippocampus. This study revealed the important effect of curcuminoids on genes expression, showing that, each component of the curcuminoid mixture distinctly affects gene expression, thus highlighting the therapeutic potential of curcuminoids in AD. (C) 2011 Elsevier B.V. All rights reserved.