Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Biology, School of Basic Science, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Pharm Res. 2020 Feb 4;37(3):48. doi: 10.1007/s11095-020-2773-6.
The current drugs for Alzheimer's disease (AD) are only used to slow or delay the progression of the pathology. So using a novel technology is a necessity to synthesize more effective medications to control this most common cause of dementia. In this study, using nanochelating technology, ALZc3 was synthesized and its therapeutic effects were evaluated in comparison with memantine on a well-known rat model of AD, which is based on Amyloid-βeta (Aβ) injection into the brain.
Aβ (1-42) was injected bilaterally into the CA1 area of the hippocampus of male rats and then animals were treated daily by oral administration of Alz-C3, memantine or their vehicles. Activities of antioxidant enzymes catalase and superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) levels, as well as Bax/Bcl-2 ratio, caspase-3 activation, and TNF-α expression were evaluated 7 days after Aβ injection. Finally, learning and memory of the rats were assessed by Morris water maze test.
ALZc3 and memantine improved memory impairment and antioxidant activity and reduced TNF-α expression, caspase-3 activity and Bax/Bcl-2 ratio in the rat's hippocampus. The results showed a superiority of ALZC3 compared to memantine in reducing caspase-3, increasing CAT activity in Aβ (1-42)-injected groups and improving apoptosis factor in healthy mice.
These results indicated that ALZc3 could significantly prevent the memory impairment and Aβ (1-42) toxicity. Thus, ALZc3 could be a promising novel anti-AD agent.
目前用于治疗阿尔茨海默病(AD)的药物仅用于减缓或延迟病理进展。因此,有必要采用新技术来合成更有效的药物来控制这种最常见的痴呆症病因。在本研究中,使用纳米螯合技术合成了 ALZc3,并将其与美金刚胺在基于β淀粉样蛋白(Aβ)注射到大脑的著名 AD 大鼠模型上的治疗效果进行了比较。
将 Aβ(1-42)双侧注射到雄性大鼠海马 CA1 区,然后通过口服给予 Alz-C3、美金刚胺或其载体对动物进行每日治疗。在 Aβ注射后 7 天评估抗氧化酶过氧化氢酶和超氧化物歧化酶(SOD)、谷胱甘肽(GSH)和丙二醛(MDA)水平的活性,以及 Bax/Bcl-2 比值、caspase-3 激活和 TNF-α 表达。最后,通过 Morris 水迷宫试验评估大鼠的学习和记忆能力。
ALZc3 和美金刚胺改善了记忆障碍,提高了抗氧化活性,并降低了大鼠海马 TNF-α表达、caspase-3 活性和 Bax/Bcl-2 比值。结果表明,与 memantine 相比,ALZC3 在降低 caspase-3、增加 Aβ(1-42)注射组中的 CAT 活性和改善健康小鼠中的凋亡因子方面具有优势。
这些结果表明,ALZc3 可显著预防记忆障碍和 Aβ(1-42)毒性。因此,ALZc3 可能是一种有前途的新型抗 AD 药物。