Treatment with Akebia Saponin D Ameliorates Aβ1-42-Induced Memory Impairment and Neurotoxicity in Rats

Amyloid- peptide (A) is known to be directly associated with the progressive neuronal death observed in Alzheimer's disease (AD). However, effective neuroprotective approaches against A neurotoxicity are still unavailable. In the present study, we investigated the protective effects of Akebia saponin D (ASD), a typical compound isolated from the rhizome of Dipsacus asper Wall, on A(1-42)-induced impairment of learning and memory formation and explored the probable underlying molecular mechanisms. We found that treatment with ASD (30, 90 or 270 mg/kg) significantly ameliorated impaired spatial learning and memory in intracerebroventricularly (ICV) A(1-42)-injected rats, as evidenced by a decrease tendency in escape latency during acquisition trials and improvement in exploratory activities in the probe trial in Morris water maze (MWM). Further study showed that ASD reversed A(1-42)-induced accumulation of A(1-42) and A(1-40) in the hippocampus through down-regulating the expression of BACE and Presenilin 2 accompanied with increased the expression of TACE, IDE and LRP-1. Taken together, our findings suggested that ASD exerted therapeutic effects on A-induced cognitive deficits via amyloidogenic pathway.