Department of Traditional Chinese Integrated Western Medicine, Qi Lu Hospital, Shandong University, Jinan 250012, PR China.
Neuroscience. 2012 Sep 18;220:191-200. doi: 10.1016/j.neuroscience.2012.06.027. Epub 2012 Jun 19.
Ginsenoside Rg1, which could improve spatial learning and memory, might be a useful agent for preventing and treating cognitive impairment in Alzheimer's disease (AD). The present study was designed to test the neuroprotective effects of ginsenoside Rg1 on an ovariectomized (OVX) and d-galactose (d-gal)-injected rat model of AD, which is characterized with progressive learning and memory deficits, AD-related molecules alteration and differentiation/apoptosis imbalance in hippocampal neurons. OVX Wistar rats received daily injections of d-gal (100mg/kg) combined with different concentrations of ginsenoside Rg1 (5, 10, 20mg/kg) or 17-β-estradiol (E2, 100 μg/kg), or normal saline (NS, 1.0 ml/kg) for 6 weeks. Ovarian steroid deprivation plus d-gal injection led to spatial learning and memory capacity impairments, as well as increased Aβ(1-42) production. Ginsenoside Rg1 and E2-treatment significantly ameliorated these deteriorations in AD rats. Seven weeks after surgery, α-secretase a disintegrin and metallopeptidase domain 10 (ADAM 10) in hippocampus of AD rats was dramatically decreased, while β-secretase β-site APP-cleaving enzyme 1 (BACE 1) increased compared with those in sham-operated ones (P<0.05). Levels of cleaved caspase 3 were increased in the hippocampus of AD rats. Ginsenoside Rg1 and E2-treatment increased ADAM 10 level while reduced BACE 1 level and apoptosis. Moreover, moderate i.e. 10mg/kg/d and high i.e. 20mg/kg/d ginsenoside Rg1 displayed more effective function than low i.e. 5mg/kg/d ginsenoside Rg1. Our findings demonstrate the neuroprotective effects of ginsenoside Rg1 and E2 on AD rats and support the potential application of ginsenoside Rg1 in the treatment of learning and memory impairments in postmenopausal women.
人参皂苷 Rg1 可改善空间学习和记忆，可能是预防和治疗阿尔茨海默病（AD）认知障碍的有用药物。本研究旨在测试人参皂苷 Rg1 对去卵巢（OVX）和半乳糖（d-gal）注射 AD 大鼠模型的神经保护作用，该模型的特征是进行性学习和记忆缺陷、AD 相关分子改变以及海马神经元的分化/凋亡失衡。OVX 雌性 Wistar 大鼠每天接受 d-gal（100mg/kg）联合不同浓度的人参皂苷 Rg1（5、10、20mg/kg）或 17-β-雌二醇（E2，100μg/kg）或生理盐水（NS，1.0ml/kg）注射，共 6 周。卵巢类固醇剥夺加 d-gal 注射导致空间学习和记忆能力受损，以及 Aβ（1-42）产生增加。人参皂苷 Rg1 和 E2 治疗显著改善了 AD 大鼠的这些恶化。手术后 7 周，AD 大鼠海马中的 α-分泌酶 a 去整合素和金属肽酶域 10（ADAM 10）显著减少，而 β-分泌酶 β-位淀粉样前体蛋白裂解酶 1（BACE 1）增加，与假手术组相比（P<0.05）。AD 大鼠海马中裂解的 caspase 3 水平增加。人参皂苷 Rg1 和 E2 治疗增加了 ADAM 10 水平，同时降低了 BACE 1 水平和细胞凋亡。此外，中等剂量即 10mg/kg/d 和高剂量即 20mg/kg/d 的人参皂苷 Rg1 比低剂量即 5mg/kg/d 的人参皂苷 Rg1 显示出更有效的作用。我们的研究结果表明，人参皂苷 Rg1 和 E2 对 AD 大鼠具有神经保护作用，并支持人参皂苷 Rg1 在治疗绝经后妇女学习和记忆障碍中的潜在应用。
