Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Lagos, Nigeria.
Division of Medicinal and Process Chemistry, Central Drug Research Institute (CSIR), Lucknow, 226001, India.
Neurotox Res. 2020 Jan;37(1):58-66. doi: 10.1007/s12640-019-00117-8. Epub 2019 Oct 26.
Dementia of Alzheimer disease type (AD) and type 2 diabetes mellitus (T2D) are two most common diseases of aging which has reached epidemic proportions. Moreover, there is a shared mechanism of pathogenesis between metabolic disorders and AD. Hence, the need for discivery of effective prevention and treatment strategies. Diastereomeric mixture of calophyllic acid and isocalophyllic acid (ISO) has been shown to stimulate glucose uptake through GLUT4- translocation. In this study, an attempt was made to investigate the effect of ISO on scopolamine-induced memory deficit in mice. ISO (5, 25 or 50 mg/kg, p.o.) or vehicle (10 ml/kg, p.o.) was administered for 3 consecutive days. One hour post-treatment on day 3, scopolamine (3 mg/kg, i.p.) was given before the animals were subjected to Y-maze, open field, novel object recognition (NOR) or Morris water maze (MWM; 5 consecutive days) paradigms. The mice were sacrificed 45 min after MWM test on day 8. The hippocampus and prefrontal cortex were rapidly isolated on ice for assay of biochemical markers of oxidative stress and acetylcholinesterase activity. Scopolamine reduced the percentage alternation behaviour in the Y-maze and discrimination index in NOR tests with no significant change in escape latency time in MWM task suggestive of deficit in learning and memory. However, the pretreatment of mice with ISO produced a dose-dependent improvement in learning and memory. Moreover, ISO administration attenuated scopolamine-induced increase in malondialdehyde/nitrite generation and acetylcholinesterase activity and deficit in antioxidant enzyme activity in the hippocampus and prefrontal cortex. Findings from this study showed that the diastereomeric mixture of calophyllic acid and isocalophyllic acid possesses anti-amnesic effect through enhancement of antioxidant defense and cholinergic signaling pathway.
阿尔茨海默病型（AD）和 2 型糖尿病（T2D）痴呆是两种最常见的衰老疾病，已达到流行程度。此外，代谢紊乱和 AD 之间存在共同的发病机制。因此，需要发现有效的预防和治疗策略。已发现金松双黄酮和异金松双黄酮（ISO）的非对映异构体混合物通过 GLUT4-易位刺激葡萄糖摄取。在这项研究中，尝试研究 ISO 对东莨菪碱诱导的小鼠记忆缺陷的影响。ISO（5、25 或 50 mg/kg，po）或载体（10 ml/kg，po）连续 3 天给药。第 3 天治疗后 1 小时，腹腔内给予东莨菪碱（3 mg/kg），然后将动物置于 Y 迷宫、旷场、新物体识别（NOR）或 Morris 水迷宫（MWM；连续 5 天）范式中。第 8 天 MWM 测试后 45 分钟处死小鼠。在冰上快速分离海马和前额叶皮层，用于测定氧化应激和乙酰胆碱酯酶活性的生化标志物。东莨菪碱降低了 Y 迷宫中的百分比交替行为和 NOR 测试中的辨别指数，而在 MWM 任务中的逃避潜伏期时间没有明显变化，提示学习和记忆缺陷。然而，ISO 预处理可使学习和记忆呈剂量依赖性改善。此外，ISO 给药可减轻东莨菪碱诱导的海马和前额叶皮层中超氧化物歧化酶/一氧化氮生成和乙酰胆碱酯酶活性增加以及抗氧化酶活性降低。本研究结果表明，金松双黄酮和异金松双黄酮的非对映异构体混合物通过增强抗氧化防御和胆碱能信号通路具有抗健忘作用。
