Wang Haixia, Lv Jingwei, Jiang Ning, Huang Hong, Wang Qiong, Liu Xinmin
Research Center of Pharmacology and Toxicology, Institute of Medicinal Plant, Development (IMPLAD), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Affiliated TCM Hospital/School of Pharmacy/Sino-Portugal TCM International Cooperation Center, Southwest Medical University, Luzhou, China.
Phytother Res. 2021 May;35(5):2523-2535. doi: 10.1002/ptr.6947. Epub 2021 Mar 29.
Exposure to chronic stress negatively affects the development of cognition, characterized by learning and memory decline. Ginsenoside Re (GRe), an active compound derived from Panax ginseng, exhibited neuroprotective activity in various neurological diseases. In this study, the protective effect of GRe on chronic restraint stress (CRS)-induced memory deficit was investigated. The mice were experienced 35 days of the CRS induction. The GRe was administered daily orally (10, 20, or 40 mg/kg) during the next 3 weeks stress session and the behavior test period. The CRS-induced memory impairment mice were subjected to behavioral tasks, such as the Y-maze, novel objects recognition, and step-through passive avoidance tests. Nissl staining was used to examine the neuron numbers. The levels of antioxidant enzymes, malondialdehyde, and proinflammatory factor were determined by kits and ELISA assays. The expressions of brain-derived neurotrophic factor (BDNF), NOD-like receptor protein 3 (NLRP3), nuclear factor erythroid-2 related factor 2 (Nrf2) and synapse-associated proteins (synaptophysin, SYP, and postsynaptic density 95, PSD95) were measured by Western blotting. Behavioral assessments indicated that GRe could ameliorate the cognitive impairment of CRS-induced mice, as indicated by increased responses in Y-maze (p < .05), novel objects recognition (p < .01), and step-through passive avoidance tests (p < .01). In addition, GRe treatment significantly decreased the neuronal loss in CRS mice in histological examination. Moreover, chronic GRe treatment significantly ameliorated the down-regulated the expressions of BDNF, Nrf2, heme oxygenase (HO)-1, SYP, and PSD95, as well as up-regulated NLRP3, the adaptor protein ASC, and Caspase-1 protein expression in the hippocampus of CRS-treated mice. Taken together, these findings suggest that GRe has a potential therapeutic effect on memory impairment in C57BL/6J mice exposed to CRS paradigm.
长期暴露于慢性应激会对认知发展产生负面影响，其特征为学习和记忆能力下降。人参皂苷Re（GRe）是从人参中提取的一种活性化合物，在多种神经系统疾病中表现出神经保护活性。在本研究中，我们探究了GRe对慢性束缚应激（CRS）诱导的记忆缺陷的保护作用。小鼠经历了35天的CRS诱导。在接下来3周的应激期和行为测试期，每天口服给予GRe（10、20或40mg/kg）。对CRS诱导的记忆损伤小鼠进行行为任务测试，如Y迷宫、新物体识别和穿梭式被动回避测试。采用尼氏染色法检测神经元数量。通过试剂盒和ELISA测定法测定抗氧化酶、丙二醛和促炎因子的水平。采用蛋白质免疫印迹法检测脑源性神经营养因子（BDNF）、NOD样受体蛋白3（NLRP3）、核因子红细胞2相关因子2（Nrf2）和突触相关蛋白（突触素、SYP和突触后致密蛋白95、PSD95）的表达。行为评估表明，GRe可以改善CRS诱导小鼠的认知障碍，Y迷宫（p＜0.05）、新物体识别（p＜0.01）和穿梭式被动回避测试（p＜0.01）中的反应增加表明了这一点。此外，组织学检查显示GRe治疗显著减少了CRS小鼠的神经元损失。此外，长期GRe治疗显著改善了CRS处理小鼠海马中BDNF、Nrf2、血红素加氧酶（HO）-1、SYP和PSD95表达的下调，以及NLRP3、衔接蛋白ASC和半胱天冬酶-1蛋白表达的上调。综上所述，这些发现表明GRe对暴露于CRS范式的C57BL/6J小鼠的记忆损伤具有潜在的治疗作用。
