Pharmaceutical Medicine, Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India.
Pharmaceutical Biotechnology Laboratory, Department of Pharmacognosy & Phtyochemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India.
Biomed Pharmacother. 2019 Feb;110:47-58. doi: 10.1016/j.biopha.2018.11.043. Epub 2018 Nov 18.
With the constant failure of the clinical trials continuous exploration of a therapeutic target against Alzheimer's disease (AD) is the utmost need. Numerous studies have supported the hypothesis that central insulin resistance plays a significant role in AD. Serine phosphorylation of Insulin Receptor Substarte-1 (IRS-1) has been found to be a contributing factor in neuronal insulin resistance. Astaxanthin (ASX) is xanthophyll carotenoid which has previously demonstrated significant antidiabetic and neuroprotective actions. In the present study, AD was induced by i.c.v administration of Amyloid-β (1-42) peptides in Wistar rats. After 7 days of recovery, rats were treated with 0.5 mg/kg and 1 mg/kg of ASX orally for 28 days. Behavioral analysis was done in the last week of our experimental study. On the 36th day, rats were sacrificed and their hippocampus were separated from the whole brain, then homogenized and stored for biochemical estimations. ASX significantly and dose-dependently reversed the cognitive and memory impairment, assessed by Morris water maze test and Novel object Recognition test, Aβ (1-42) peptides infused Wistar rats. ASX also significantly attenuated soluble Aβ (1-42) level, IRS-S307 activity, GSK-3β activity, TNF-α level, AChE level, nitrite level and oxidative stress in the hippocampus. Histopathological evaluation, done through H&E and Congo red staining, also demonstrated neuroprotective and anti-amyloidogenic effects of ASX in hippocampus. Our study concludes preventive action of Astaxanthin against hippocampal insulin resistance and Alzheimer's disease complications, supporting potential role of hippocampal insulin resistance targeting against AD.
随着临床试验的不断失败，不断探索针对阿尔茨海默病（AD）的治疗靶点是当务之急。大量研究支持了这样一种假设，即中枢胰岛素抵抗在 AD 中起着重要作用。胰岛素受体底物-1（IRS-1）的丝氨酸磷酸化已被发现是神经元胰岛素抵抗的一个促成因素。虾青素（ASX）是一种叶黄素类胡萝卜素，先前已证明其具有显著的抗糖尿病和神经保护作用。在本研究中，通过侧脑室注射淀粉样β（1-42）肽在 Wistar 大鼠中诱导 AD。恢复 7 天后，大鼠分别以 0.5mg/kg 和 1mg/kg 的 ASX 口服给药 28 天。在实验研究的最后一周进行行为分析。在第 36 天，处死大鼠，从整个大脑中分离出海马，然后匀浆并储存进行生化测定。ASX 显著且剂量依赖性地逆转了 Morris 水迷宫试验和新物体识别试验评估的认知和记忆障碍，Aβ（1-42）肽输注 Wistar 大鼠。ASX 还显著减弱了可溶性 Aβ（1-42）水平、IRS-S307 活性、GSK-3β 活性、TNF-α 水平、AChE 水平、亚硝酸盐水平和海马中的氧化应激。通过 H&E 和刚果红染色进行的组织病理学评估也证明了 ASX 在海马中的神经保护和抗淀粉样变性作用。我们的研究得出结论，虾青素对海马胰岛素抵抗和阿尔茨海默病并发症具有预防作用，支持针对 AD 靶向海马胰岛素抵抗的潜在作用。
