Division of Pharmacology, Central Drug Research Institute, CSIR, Lucknow-226001, India.
Pharmacol Res. 2010 Mar;61(3):247-52. doi: 10.1016/j.phrs.2009.12.008. Epub 2009 Dec 21.
Curcumin, the principal curcuminoid of turmeric, exhibits beneficial role in several neurodegenerative disorders such as dementia of Alzheimer type. Recent evidences suggest the involvement of brain insulin receptors (IRs) in the pathophysiology of dementia disorders. Therefore, the present study was undertaken to investigate the effect of curcumin on memory functions, brain IRs, acetylcholinesterase (AChE) activity and oxidative stress in intracerebroventricular (ICV) administered streptozotocin (STZ) induced dementia in rats. Rats were injected with STZ (3 mg/kg, ICV) bilaterally twice, on day 1 and 3 and curcumin (200 mg/kg, po) was administered in pre- and post-treatment schedules. STZ (ICV) treated group had shown memory deficit as indicated by no significant decrease in latency time in Morris water maze test and significant decrease in IR protein level in both hippocampus and cerebral cortex. Pre- and post-treatment of curcumin in STZ (ICV) treated rats significantly restored the memory deficit and IR protein level in both the regions. Furthermore, STZ (ICV) resulted into enhanced AChE activity in hippocampus and cerebral cortex which was normalized by curcumin pre- and post-treatment. An increase in MDA level and decrease in GSH level were obtained in both hippocampus and cerebral cortex in STZ treated group, indicating state of oxidative stress, which was also attenuated by pre- and post-treatment of curcumin. The results suggest that besides the anticholinesterase and antioxidant activity, effect on brain IR may also be an important factor for protective effect of curcumin against STZ induced dementia model.
姜黄素是姜黄的主要姜黄素类化合物，在几种神经退行性疾病中表现出有益作用，如阿尔茨海默病型痴呆。最近的证据表明，脑胰岛素受体（IR）参与了痴呆症的病理生理学。因此，本研究旨在探讨姜黄素对侧脑室（ICV）给予链脲佐菌素（STZ）诱导的大鼠痴呆模型的记忆功能、脑 IR、乙酰胆碱酯酶（AChE）活性和氧化应激的影响。大鼠双侧脑室（ICV）两次注射 STZ（3mg/kg），第 1 天和第 3 天，姜黄素（200mg/kg，po）在预处理和后处理方案中给药。STZ（ICV）处理组表现出记忆缺陷，表现在 Morris 水迷宫测试中潜伏期无显著缩短，海马和大脑皮层的 IR 蛋白水平显著降低。STZ（ICV）处理大鼠的姜黄素预处理和后处理显著恢复了两种区域的记忆缺陷和 IR 蛋白水平。此外，STZ（ICV）导致海马和大脑皮层中的 AChE 活性增强，姜黄素的预处理和后处理使其正常化。STZ 处理组在海马和大脑皮层中 MDA 水平升高和 GSH 水平降低，表明氧化应激状态，姜黄素的预处理和后处理也减弱了这种状态。结果表明，除了抗胆碱酯酶和抗氧化活性外，对脑 IR 的影响可能也是姜黄素对 STZ 诱导的痴呆模型的保护作用的一个重要因素。
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