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

Neuroreport. 2009 Nov 25;20(17):1564-7. doi: 10.1097/WNR.0b013e328332d345.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / antagonists & inhibitors*
  • Amyloid beta-Peptides / toxicity
  • Animals
  • Cells, Cultured
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal / pharmacology
  • Drugs, Chinese Herbal / therapeutic use
  • Enzyme Inhibitors / pharmacology
  • Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Flavonoids / pharmacology*
  • Flavonoids / therapeutic use
  • Mice
  • Nerve Tissue Proteins / agonists*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurons / pathology
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use
  • Peptide Fragments / antagonists & inhibitors
  • Peptide Fragments / toxicity
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Up-Regulation / drug effects
  • Up-Regulation / physiology

Substances

  • Amyloid beta-Peptides
  • Drugs, Chinese Herbal
  • Enzyme Inhibitors
  • Flavonoids
  • Nerve Tissue Proteins
  • Neuroprotective Agents
  • Peptide Fragments
  • RNA, Messenger
  • amyloid beta-protein (1-42)
  • cocaine- and amphetamine-regulated transcript protein
  • Extracellular Signal-Regulated MAP Kinases
  • icariin