Danggui-Shaoyao-San and its active fraction JD-30 improve Abeta-induced spatial recognition deficits in mice.
OBJECTIVE
Previous studies showed that Danggui-Shaoyao-San (DSS), a traditional Chinese medicinal prescription, could alleviate cognitive dysfunction of Alzheimer's disease (AD) patients. However, the mechanism and substance basis remain unknown. JD-30 is a fraction extracted from DSS, whose activity we previously was evaluated. beta-Amyloid (Abeta) is believed to be a critical etiological factor of AD. We have now examined the effect of DSS and JD-30 on AD model mice induced by Abeta, and elucidated the possible mechanism.


METHODS
Mice were intracerebroventricular injected with the aggregated Abeta(25-35) to mimic AD. Groups of mice were treated with DSS or JD-30 by intragastric infusion over 2 weeks, and their spatial learning and memory capacities were measured by the Morris water maze procedure. The mechanisms were investigated by extracellular microelectrode recordings, and also electron microscopy.


RESULTS
Our results show that Abeta(25-35) induced impairment of spatial learning and memory in mice, as well as inhibition of long-term potentiation (LTP) in the hippocampus. The impairments were ameliorated by DSS or JD-30 administration. Additionally, JD-30 not only prevented the aggregation of Abeta(25-35), but disrupted aggregated Abeta(25-35) fibrils.


CONCLUSIONS
These results suggest that JD-30 is one of the chief active fractions extracted from DSS by its ability to ameliorate deterioration of cognition, and by blocking and disrupting the aggregation of Abeta so that synaptic plasticity was improved, which may be one of the mechanisms involved.
Hu
Zeng-Yao
ZY
Beijing Institute of Pharmacology and Toxicology, 27 Tai-Ping Road, Beijing 100850, China.
Liu
Gang
G
Yuan
Hui
H
Yang
Sheng
S
Zhou
Wen-Xia
WX
Zhang
Yong-Xiang
YX
Qiao
Shan-Yi
SY
D000544:Alzheimer Disease / Q000150:complications; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000209:etiology* / Q000503:physiopathology; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006624:Hippocampus / Q000503:physiopathology*; D006801:Humans; D007858:Learning / Q000187:drug effects; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D058255:Protease Nexins; D011897:Random Allocation; D011956:Receptors, Cell Surface / Q000378:metabolism*
D016564:Amyloid beta-Protein Precursor; D004365:Drugs, Chinese Herbal; D058255:Protease Nexins; D011956:Receptors, Cell Surface; C531150:danggui-shaoyao-san