Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab 147002, India.
J Basic Clin Physiol Pharmacol. 2020 Mar 11;31(3):/j/jbcpp.2020.31.issue-3/jbcpp-2019-0197/jbcpp-2019-0197.xml. doi: 10.1515/jbcpp-2019-0197.
Background An earlier study demonstrated significant antioxidant and anticholinesterase activities of hydromethanol extract (HME) of Allium cepa. The aim of the study was to investigate the component responsible for these activities followed by an in vivo study. Methods In vitro antioxidant and anticholinesterase activities of standardized ethylacetate fraction (EAF) of HME were assessed. Bioactivity-guided fractionation showed that, as compared with its subfractions, EAF had most significant activity in 2,2-diphenyl-1-picrylhydrazyl and Ellman assays. Thus, EAF was further examined using a streptozotocin (STZ)-induced model of Alzheimer's disease in mice. STZ was injected intracerebroventricularly on days 1 and 3 (3 mg/kg) in mice. EAF was thereafter administered (42, 84, and 168 mg/kg b.w./day p.o.) from days 9 to 22. The Morris water maze test was used to evaluate learning and memory in mice. Acetylcholinesterase (AChE) activity and oxidative stress markers were assessed in the brain homogenates of mice. Additionally, histopathological studies were performed to observe effects in the brain at the cellular level. EAF was standardized based on quercetin and quercetin 4'-O-glucoside content using a validated thin layer chromatography densitometric method. Results STZ produced significant (p < 0.05) memory impairment along with oxidative stress and a cholinergic deficit in mice. EAF treatment ameliorated STZ-induced behavioral deficits and biochemical alterations in mice in a significant and dose-dependent manner. Conclusions Our results show that EAF is efficacious in improving memory and learning via AChE inhibition and antioxidant activity in the mice brain. Thus, AC could be explored further to find out a lead candidate for Alzheimer's disease.
先前的研究表明,洋葱水醇提取物(HME)具有显著的抗氧化和乙酰胆碱酯酶抑制活性。本研究旨在探讨其产生这些活性的成分,并进行体内研究。
评估 HME 标准化乙酸乙酯馏分(EAF)的体外抗氧化和乙酰胆碱酯酶抑制活性。生物活性导向的馏分分离表明,与亚馏分相比,EAF 在 2,2-二苯基-1-苦基肼基(DPPH)和 Ellman 测定中具有最显著的活性。因此,使用链脲佐菌素(STZ)诱导的阿尔茨海默病小鼠模型进一步检查 EAF。在第 1 天和第 3 天(3 mg/kg)通过侧脑室注射 STZ,此后在第 9 天至第 22 天(每天 42、84 和 168 mg/kg b.w./p.o.)给予 EAF。使用 Morris 水迷宫测试评估小鼠的学习和记忆。评估小鼠大脑匀浆中的乙酰胆碱酯酶(AChE)活性和氧化应激标志物。此外,还进行了组织病理学研究以观察细胞水平的脑效应。使用经验证的薄层色谱密度测定法,基于槲皮素和槲皮素 4'-O-葡萄糖苷含量对 EAF 进行标准化。
STZ 导致小鼠产生明显的(p < 0.05)记忆障碍、氧化应激和胆碱能不足。EAF 治疗以显著和剂量依赖性的方式改善了 STZ 诱导的行为缺陷和生化改变。
我们的结果表明,EAF 通过抑制 AChE 和抗氧化活性来改善小鼠的记忆和学习,因此可以进一步探索 AC 以寻找阿尔茨海默病的候选药物。