Retinasamy Thaarvena, Shaikh Mohd Farooq, Kumari Yatinesh, Othman Iekhsan
Neuropharmacology Research Laboratory, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Malaysia.
Front Pharmacol. 2019 Oct 29;10:1216. doi: 10.3389/fphar.2019.01216. eCollection 2019.
Alzheimer's disease (AD) is a chronic neurodegenerative brain disease which is characterized by impairment in cognitive functioning. (OS) Benth. (Lamiaceae) is a medicinal plant found around Southeast Asia that has been employed as treatments for various diseases. OS extract contains many active compounds that have been shown to possess various pharmacological properties whereby studies have demonstrated neuroprotective as well as cholinesterase inhibitory effects. This study, therefore aimed at determining whether this Malaysian plant derived flavonoid can reverse scopolamine induced learning and memory dysfunction in the novel object recognition (NOR) test and the elevated plus maze (EPM) test. In the present study, rats were treated once daily with OS 50 mg/kg, 100 mg/kg, 200 mg/kg and donepezil 1 mg/kg oral dosing and were given intraperitoneal (ip) injection of scopolamine 1 mg/kg daily to induce cognitive deficits. Rats were subjected to behavioral analysis to assess learning and memory functions and hippocampal tissues were extracted for gene expression and immunohistochemistry studies. All the three doses demonstrated improved scopolamine-induced impairment by showing shortened transfer latency as well as the higher inflexion ratio when compared to the negative control group. OS extract also exhibited memory-enhancing activity against chronic scopolamine-induced memory deficits in the long-term memory novel object recognition performance as indicated by an increase in the recognition index. OS extract was observed to have modulated the mRNA expression of CREB1, BDNF, and TRKB genes and pretreatment with OS extract were observed to have increased the immature neurons against hippocampal neurogenesis suppressed by scopolamine, which was confirmed by the DCX-positive stained cells. These research findings suggest that the OS ethanolic extract demonstrated an improving effect on memory and hence could serve as a potential therapeutic target for the treatment of neurodegenerative diseases like AD.
阿尔茨海默病（AD）是一种慢性神经退行性脑疾病，其特征是认知功能受损。溪黄草（OS）（唇形科）是一种在东南亚各地发现的药用植物，已被用于治疗各种疾病。OS提取物含有许多活性化合物，这些化合物已被证明具有多种药理特性，研究表明其具有神经保护以及胆碱酯酶抑制作用。因此，本研究旨在确定这种源自马来西亚植物的类黄酮是否能在新物体识别（NOR）试验和高架十字迷宫（EPM）试验中逆转东莨菪碱诱导的学习和记忆功能障碍。在本研究中，大鼠每天口服一次50 mg/kg、100 mg/kg、200 mg/kg的OS以及1 mg/kg的多奈哌齐，并每天腹腔注射（ip）1 mg/kg的东莨菪碱以诱导认知缺陷。对大鼠进行行为分析以评估学习和记忆功能，并提取海马组织进行基因表达和免疫组织化学研究。与阴性对照组相比，所有三个剂量均显示出改善东莨菪碱诱导的损伤，表现为转移潜伏期缩短以及更高的弯曲率。OS提取物在长期记忆新物体识别性能方面也表现出对慢性东莨菪碱诱导的记忆缺陷的记忆增强活性，识别指数增加表明了这一点。观察到OS提取物调节了CREB1、BDNF和TRKB基因的mRNA表达，并且观察到用OS提取物预处理增加了被东莨菪碱抑制的海马神经发生的未成熟神经元，这通过双皮质素（DCX）阳性染色细胞得到证实。这些研究结果表明，OS乙醇提取物对记忆有改善作用，因此可作为治疗AD等神经退行性疾病的潜在治疗靶点。
