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

Abstract

Amyloid-β peptide (Aβ) is known to be directly associated with the progressive neuronal death observed in Alzheimer’s disease (AD). However, effective neuroprotective approaches against Aβ 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 Aβ1–42-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) Aβ1–42-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 Aβ1–42-induced accumulation of Aβ1–42 and Aβ1–40 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 Aβ-induced cognitive deficits via amyloidogenic pathway.

Keywords

• Alzheimer’s disease
• Akebia Saponin D (ASD)
• Amyloid β (Aβ)1–42
• cognitive impairment
• neurotoxicity