The therapeutic effects of the herbal medicine, Juzen-taiho-to, on amyloid-beta burden in a mouse model of Alzheimer's disease.
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 (Abeta) 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-Abeta antibody showed reduced Abeta burden, and Abeta 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.
Hara
Hideo
H
Division of Neurology, Department of Internal Medicine, Saga University Faculty of Medicine, Saga, Japan. hihara@cc.saga-u.ac.jp
Kataoka
Seiko
S
Anan
Mayumi
M
Ueda
Akihiro
A
Mutoh
Tatsuro
T
Tabira
Takeshi
T
D000284:Administration, Oral; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D052160:Benzothiazoles; D001854:Bone Marrow Cells / Q000187:drug effects; D002135:Calcium-Binding Proteins; D018929:Cell Culture Techniques; D016207:Cytokines / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005434:Flow Cytometry / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D008840:Microfilament Proteins; D009154:Mutation / Q000235:genetics; D013844:Thiazoles
C112986:AIF1 protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D015703:Antigens, CD; D014150:Antipsychotic Agents; D052160:Benzothiazoles; D002135:Calcium-Binding Proteins; D016207:Cytokines; D004268:DNA-Binding Proteins; D004365:Drugs, Chinese Herbal; D019394:Ki-67 Antigen; D008840:Microfilament Proteins; D013844:Thiazoles; C063587:juzentaihoto; C009462:thioflavin T