The Therapeutic Effects of the Herbal Medicine, Juzen-taiho-to, on Amyloid-β Burden in a Mouse Model of Alzheimer's Disease
The Therapeutic Effects of the Herbal Medicine, Juzen-taiho-to, on Amyloid-β Burden in a Mouse Model of Alzheimer's Disease
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DOI：
10.3233/jad-2010-1381
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发表时间：
2010-01-01
影响因子：
4
通讯作者：
Tabira, Takeshi
中科院分区：
文献类型：
--
作者：
Hara, Hideo;Kataoka, Seiko;Tabira, Takeshi
据报道，先天免疫，尤其是涉及巨噬细胞功能的免疫，会随着年龄的增长和阿尔茨海默病(AD)患者的年龄增长而减弱。在本研究中，我们试图通过口服中药巨噬细胞(JTT)来诱导外周巨噬细胞的非特异性激活，以评估其作为一种可能的治疗AD患者的效果。用淀粉样β蛋白前体转基因小鼠作为AD模型，以明确JTT的作用。来自骨髓的活化巨噬细胞穿过血脑屏障，发育成小胶质细胞，吞噬老年斑块中聚集的淀粉样β蛋白(Aβ)。在这里，我们显示口服加味汤能增加小鼠脑内CD11b阳性分支小胶质细胞的数量。多克隆抗Aβ抗体染色的脑切片免疫组织化学检测显示，Aβ负荷量减少，经酶联免疫吸附试验检测，脑匀浆不溶性部分的Aβ水平也降低。因此，JTT激活外周巨噬细胞可能是治疗AD的一种新策略。
Innate immunity, especially that involving macrophage function, reportedly diminishes with advancing age and in patients with Alzheimer's disease (AD). In this study, we tried to elicit the non-specific activation of peripheral macrophages by oral administration of the herbal medicine Juzen-taiho-to (JTT), to assess its effect as a possible treatment for AD patients. Amyloid-beta protein precursor transgenic mice were used as a model of AD to clarify the effect of JTT. Activated macrophages derived from bone marrow cross the blood-brain barrier, and then develop into microglia, which phagocytose aggregated amyloid-beta (A beta) in senile plaques. Here we show that orally administered JTT increased the number of CD11b-positive ramified microglia in the mouse brain. The immunohistochemical examination of brain sections stained with polyclonal anti-A beta antibody showed reduced A beta burden, and A beta levels were also decreased in the insoluble fractions of brain homogenates, as determined by ELISA. Thus, the activation of peripheral macrophages by JTT might be a potential new therapeutic strategy for AD.