Icariin inhibits beta-amyloid peptide segment 25–35 induced expression of β-secretase in rat hippocampus

Abstract

The present study was undertaken to investigate the protective effects of icariin on the learning and memory abilities in Alzheimer's disease model rats and explore its protection mechanisms. Beta-amyloid peptide (Aβ) is a key etiology in Alzheimer's disease and targeting on Aβ production and assembly is a new therapeutic strategy. Six-month (400–600 g) Wistar rats were unilaterally injected with amyloid β-protein fragment 25–35 (Aβ 25–35) 10 μg (5 g/l, 2 μl) into the right hippocampus. The day following Aβ injection, icariin 30, 60 or 120 mg/kg was administered by gavage for 14 days. The ability of spatial learning and memory of the animals was tested by the Morris water maze. In place navigation test, icariin significantly decreased the mean escape latency and searching distance. In the space probing test, icariin increased remarkably the searching time and searching distance in the quadrant where the platform was originally located. All tests indicated icariin improved the ability of spatial learning and memory in Alzheimer's disease model rats. Furthermore, immunohistochemistry and real time RT-PCR analysis showed that icariin significantly reduced the contents of Aβ 1–40 and the mRNA levels of β-secretase in the hippocampus and increased the mRNA level of superoxide dismutase-2, but it had no apparent effects on the immunostain and mRNA level of amyloid protein precursor. These results demonstrate that icariin can improve the learning and memory abilities in Aβ 25–35-induced Alzheimer's disease rats. The mechanisms appear to be due to the decreased production of insoluble fragments of Aβ through suppression of β-secretase expression.