Natural Products Research Unit, Department of Biological and Biomedical Sciences, The Aga Khan University Medical College, Karachi-74800, Pakistan.
Neuroscience. 2010 Sep 1;169(3):1296-306. doi: 10.1016/j.neuroscience.2010.05.078. Epub 2010 Jun 9.
Alzheimer's disease (AD) is a neurodegenerative disease. There are a limited number of therapeutic options available for the treatment of AD. Curcuminoids (a mixture of bisdemethoxycurcumin, demethoxycurcumin and curcumin) is the main chemical constituent found in turmeric, a well known curry spice, having potential in the treatment of AD. The objective of this study was to investigate the effects of curcuminoid mixture and individual constituents on spatial learning and memory in an amyloid-beta (Abeta) peptide-infused rat model of AD and on the expression of PSD-95, synaptophysin and camkIV. Curcuminoid mixture showed a memory-enhancing effect in rats displaying AD-like neuronal loss only at 30 mg/kg, whereas individual components were effective at 3-30 mg/kg. A shorter duration treatment with test compounds showed that the curcuminoid mixture and bisdemethoxycurcumin increased PSD-95 expression in the hippocampus at 3-30 mg/kg, with maximum effect at a lower dose (3 mg/kg) with respective values of 470.5 and 587.9%. However, after a longer duration treatment, two other compounds (demethoxycurcumin and curcumin) also increased PSD-95 to 331.7 and 226.2% respectively at 30 mg/kg. When studied for their effect on synaptophysin in the hippocampus after the longer duration treatment, the curcuminoid mixture and all three individual constituents increased synaptophysin expression. Of these, demethoxycurcumin was the most effective showing a 350.1% increase (P<0.01) at 30 mg/kg compared to the neurotoxin group. When studied for their effect on camkIV expression after longer treatment in the hippocampus, only demethoxycurcumin at 30 mg/kg increased levels to 421.2%. These compounds salvaged PSD-95, synaptophysin and camkIV expression levels in the hippocampus in the rat AD model, which suggests multiple target sites with the potential of curcuminoids in spatial memory enhancing and disease modifying in AD.
阿尔茨海默病（AD）是一种神经退行性疾病。目前，治疗 AD 的方法有限。姜黄素类（双去甲氧基姜黄素、去甲氧基姜黄素和姜黄素的混合物）是在咖喱香料中发现的主要化学成分，具有治疗 AD 的潜力。本研究的目的是研究姜黄素混合物及其单个成分对 AD 样神经元缺失大鼠模型中空间学习和记忆的影响，以及对 PSD-95、突触小体相关蛋白和钙调蛋白激酶 IV（camkIV）表达的影响。只有在 30mg/kg 时，姜黄素混合物才显示出改善记忆的作用，而单个成分在 3-30mg/kg 时有效。用测试化合物进行较短时间的治疗表明，姜黄素混合物和双去甲氧基姜黄素增加了海马中的 PSD-95 表达，在 3-30mg/kg 时，低剂量（3mg/kg）时效果最大，分别为 470.5%和 587.9%。然而，经过较长时间的治疗后，另外两种化合物（去甲氧基姜黄素和姜黄素）也使 PSD-95 分别增加到 30mg/kg 时的 331.7%和 226.2%。当研究它们对海马中突触小体相关蛋白的影响时，姜黄素混合物和所有三种单体成分都增加了突触小体相关蛋白的表达。其中，去甲氧基姜黄素的效果最显著，与神经毒素组相比，在 30mg/kg 时增加了 350.1%（P<0.01）。当研究它们对海马中 camkIV 表达的影响时，只有去甲氧基姜黄素在 30mg/kg 时增加到 421.2%。这些化合物挽救了 AD 大鼠模型中海马中 PSD-95、突触小体相关蛋白和 camkIV 的表达水平，这表明姜黄素类化合物具有多个潜在的靶点，可能在空间记忆增强和 AD 疾病修饰方面发挥作用。
