Ahmed Touqeer, Gilani Anwarul-Hassan
Department of Biological and Biomedical Sciences, The Aga Khan University Medical College, Karachi-74800, Pakistan.
Pharmacol Biochem Behav. 2009 Feb;91(4):554-9. doi: 10.1016/j.pbb.2008.09.010. Epub 2008 Oct 1.
Curcuminoids (a mixture of curcumin, bisdemethoxycurcumin and demethoxycurcumin) share vital pharmacological properties possessed by turmeric, a well known curry spice, considered useful in Alzheimer's disease (AD). The aim of this study was to evaluate if curcuminoids possess acetylcholinesterase (AChE) inhibitory and memory enhancing activities. The in-vitro and ex-vivo models of AChE inhibitory activity were used along with Morris water maze test to study the effect on memory in rats. Curcuminoids inhibited AChE in the in-vitro assay with IC(50) value of 19.67, bisdemethoxycurcumin 16.84, demethoxycurcumin 33.14 and curcumin 67.69 microM. In the ex-vivo AChE assay, curcuminoids and its individual components except curcumin showed dose-dependent (3-10 mg/kg) inhibition in frontal cortex and hippocampus. When studied for their effect on memory at a fixed dose (10 mg/kg), all compounds showed significant (p<0.001) and comparable effect in scopolamine-induced amnesia. These data indicate that curcuminoids and all individual components except curcumin possess pronounced AChE inhibitory activity. Curcumin was relatively weak in the in-vitro assay and without effect in the ex-vivo AChE model, while equally effective in memory enhancing effect, suggestive of additional mechanism(s) involved. Thus curcuminoids mixture might possess better therapeutic profile than curcumin for its medicinal use in AD.
姜黄素类化合物(姜黄素、双去甲氧基姜黄素和去甲氧基姜黄素的混合物)具有著名的咖喱香料姜黄所拥有的重要药理特性,被认为对阿尔茨海默病(AD)有益。本研究的目的是评估姜黄素类化合物是否具有乙酰胆碱酯酶(AChE)抑制活性和增强记忆的活性。采用AChE抑制活性的体外和体内模型,结合莫里斯水迷宫试验,研究其对大鼠记忆的影响。在体外试验中,姜黄素类化合物抑制AChE的IC(50)值为19.67,双去甲氧基姜黄素为16.84,去甲氧基姜黄素为33.14,姜黄素为67.69 microM。在体内AChE试验中,除姜黄素外,姜黄素类化合物及其各组分在额叶皮质和海马体中均呈现剂量依赖性(3 - 10 mg/kg)抑制作用。当以固定剂量(10 mg/kg)研究它们对记忆的影响时,所有化合物在东莨菪碱诱导的失忆模型中均表现出显著(p<0.001)且相当的效果。这些数据表明,除姜黄素外,姜黄素类化合物及其所有组分均具有显著的AChE抑制活性。姜黄素在体外试验中相对较弱,在体内AChE模型中无作用,但在增强记忆效果方面同样有效,提示可能涉及其他机制。因此,姜黄素类化合物混合物在AD的药用方面可能比姜黄素具有更好的治疗效果。