Icariin inhibits beta-amyloid peptide segment 25-35 induced expression of beta-secretase in rat hippocampus.
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.
Nie
Jing
J
Department of Pharmacology, Zunyi Medical College, Zunyi 563000, PR China. niejing813@yahoo.com.cn
Luo
Yong
Y
Huang
Xie-Nan
XN
Gong
Qi-Hai
QH
Wu
Qin
Q
Shi
Jing-Shan
JS
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D007858:Learning / Q000187:drug effects; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012995:Solubility
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D005419:Flavonoids; D010446:Peptide Fragments; D012333:RNA, Messenger; C078592:amyloid beta-protein (1-40); C074636:amyloid beta-protein (25-35); D053829:Amyloid Precursor Protein Secretases; C056599:icariin