Danggui-Shaoyao-San and its active fraction JD-30 improve Aβ-induced spatial recognition deficits in mice

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. β-Amyloid (Aβ) 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 Aβ, and elucidated the possible mechanism. Mice were intracerebroventricular injected with the aggregated Aβ25–35 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. Our results show that Aβ25–35 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 Aβ25–35, but disrupted aggregated Aβ25–35 fibrils. 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 Aβ so that synaptic plasticity was improved, which may be one of the mechanisms involved.