Icariin inhibits neurotoxicity of beta-amyloid by upregulating cocaine-regulated and amphetamine-regulated transcripts.

beta-Amyloid peptide (Abeta) is one of the main protein components of senile plaques contributing to Alzheimer's disease and it can induce neuronal apoptosis. In this study, it was found that icariin, a flavonoid extracted from Chinese Herba-Epimedii, inhibited Abeta42-induced neurotoxicity in a dose-dependent manner. The peak dose of icariin was 160 microg/ml. In addition, mRNA and protein expressions of cocaine and amphetamine-regulated transcript (CART) were increased in Abeta42-treated neurons in the presence of 80 microg/ml icariin. Moreover, CART-RNA interference was able to reverse neuroprotection of icariin on Abeta42. Furthermore, the expression of CART can be suppressed by extracellular signal-regulated kinase inhibitor instead of p38/JNK inhibitors, suggesting that icariin may be developed into therapeutic agents for Alzheimer's disease and other neurodegenerative diseases.