Department of Pharmacology, Xuanwu Hospital of Capital Medical University, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing 100053, China.
Int J Biol Sci. 2014 Jan 21;10(2):181-91. doi: 10.7150/ijbs.6232. eCollection 2014.
The purpose of this study was to investigate the effects and pharmacological mechanisms of icariin, which is the main component in the traditional Chinese herb Epimedium, on β-amyloid (Aβ) production in an amyloid precursor protein (APP) transgenic (Tg) mouse model of Alzheimer's disease (AD).
APPV717I Tg mice were randomly divided into a model group and icariin-treated (30 and 100 μmol/kg per day) groups. Learning-memory abilities were determined by Morris water maze and object recognition tests. Aβ contents were measured by enzyme-linked immunosorbent assays and immunohistochemistry. Amyloid plaques were detected by Congo red staining and Bielschowsky silver staining. The levels of expression of APP and β-site APP-cleaving enzyme 1 (BACE-1) were measured by western blotting and immunohistochemistry.
Ten-month-old Tg mice showed obvious learning-memory impairments, and significant increases in Aβ contents, amyloid plaques, and APP and BACE-1 levels in the hippocampus. The intragastric administration of icariin to Tg mice for 6 months (from 4 to 10 months of age) improved the learning-memory abilities and significantly decreased the Aβ contents, amyloid plaques, and APP and BACE-1 levels in the hippocampus.
Icariin reduced the Aβ burden and amyloid plaque deposition in the hippocampus of APP transgenic mice by decreasing the APP and BACE-1 levels. These novel findings suggest that icariin may be a promising treatment in patients with AD.
本研究旨在探讨淫羊藿苷（一种传统中药淫羊藿的主要成分）对阿尔茨海默病（AD）淀粉样前体蛋白（APP）转基因（Tg）小鼠模型中β-淀粉样蛋白（Aβ）产生的影响及其药理学机制。
APPV717I Tg 小鼠随机分为模型组和淫羊藿苷处理（30 和 100 μmol/kg/天）组。通过 Morris 水迷宫和物体识别试验测定学习记忆能力。通过酶联免疫吸附试验和免疫组织化学法测定 Aβ 含量。通过刚果红染色和 Bielschowsky 银染色检测淀粉样斑块。通过 Western blot 和免疫组织化学法测定 APP 和β-位点 APP 裂解酶 1（BACE-1）的表达水平。
10 月龄 Tg 小鼠表现出明显的学习记忆障碍，海马区 Aβ 含量、淀粉样斑块和 APP、BACE-1 水平显著升高。淫羊藿苷灌胃 Tg 小鼠 6 个月（4 至 10 月龄）可改善学习记忆能力，显著降低海马区 Aβ 含量、淀粉样斑块和 APP、BACE-1 水平。
淫羊藿苷通过降低 APP 和 BACE-1 水平，减少 APP 转基因小鼠海马区的 Aβ 负荷和淀粉样斑块沉积。这些新发现表明，淫羊藿苷可能是 AD 患者有希望的治疗方法。
