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.
Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, PR China.
Dujuan
D
Sha
Lingling
L
Li
Lan
L
Ye
Rong
R
Liu
Yun
Y
Xu
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D009419:Nerve Tissue Proteins / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000633:toxicity; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
D016229:Amyloid beta-Peptides; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D005419:Flavonoids; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D012333:RNA, Messenger; C075222:amyloid beta-protein (1-42); D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein; D048049:Extracellular Signal-Regulated MAP Kinases; C056599:icariin