Natural Products Research Unit, Department of Biological and Biomedical Sciences, The Aga Khan University Medical College, Karachi-Pakistan.
Brain Res. 2011 Jul 11;1400:1-18. doi: 10.1016/j.brainres.2011.05.022. Epub 2011 May 18.
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 Aβ+ibotenic acid-infused rat model. After 5 days of treatment with demethoxycurcumin, hippocampal IL-1β levels were decreased to 118.54 ± 47.48 and 136.67 ± 31.96% respectively at 30 and 10mg/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 3mg/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 10mg/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.
阿尔茨海默病（AD）是一种神经退行性疾病，表现为慢性炎症状态的特征，导致细胞死亡，治疗选择有限。我们旨在使用 Aβ+ 异博定酸输注大鼠模型探索姜黄素混合物及其单个成分对 AD 中炎症和凋亡基因表达的影响。在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，30 和 10mg/kg 剂量的姜黄素混合物和去甲氧基姜黄素分别使海马 IL-1β 水平降低至 118.54 ± 47.48%和 136.67 ± 31.96%。在用姜黄素混合物治疗 5 天后，姜黄素混合物和去甲氧基姜黄素有效降低了海马中的 GFAP 水平。在研究其对凋亡基因表达的影响时，在用姜黄素混合物和双去甲氧基姜黄素治疗 20 天后，有效降低了海马中的 caspase-3 水平，其中双去甲氧基姜黄素在 3mg/kg 时显示出最大的挽救作用（92.35 ± 3.07%）。在用姜黄素混合物治疗 5 天后，将海马 FasL 水平降低至 70.56 ± 3.36%，20 天后降低至 19.01 ± 2.03%。在 Fas 受体水平方面，在用三种剂量的去甲氧基姜黄素治疗 5 天后降低了水平，在 10mg/kg 时显示出最大效果（189.76 ± 15.01%）。在用姜黄素混合物治疗 20 天后，每种化合物都有效降低了海马中的 Fas 受体水平。这项研究揭示了姜黄素类化合物对基因表达的重要影响，表明姜黄素混合物的每个成分都明显影响基因表达，从而突出了姜黄素类化合物在 AD 中的治疗潜力。
