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 (Abeta) is a key etiology in
Alzheimer's disease and targeting on Abeta production and assembly is a new therapeutic strategy. Six-month (400-600 g) Wistar rats were unilaterally injected with
amyloid beta-protein fragment 25-35 (Abeta(25-35)) 10 microg (5 g/l, 2 microl) into the right hippocampus. The day following Abeta 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 Abeta(1-40) and the
mRNA levels of
beta-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 Abeta(25-35)-induced
Alzheimer's disease rats. The mechanisms appear to be due to the decreased production of insoluble fragments of Abeta through suppression of
beta-secretase expression.