Icariin, a major constituent from Epimedium brevicornum, attenuates ibotenic acid-induced excitotoxicity in rat hippocampus

Behav Brain Res. 2016 Oct 15:313:111-119. doi: 10.1016/j.bbr.2016.06.055. Epub 2016 Jun 28.

Abstract

Excitotoxicity is one of the most extensively studied causes of neuronal death and plays an important role in Alzheimer's disease (AD). Icariin is a flavonoid component of a traditional Chinese medicine reported to possess a broad spectrum of pharmacological effects. The present study was designed to investigate the effects of icariin against learning and memory impairment induced by excitotoxicity. Here, we demonstrated that rats receiving intracerebroventricular injection of excitatory neurotoxin ibotenic acid exhibited impaired learning and memory. Oral administration of icariin at doses of 20 and 40mg/kg rescued behavioral performance and protected against neurotoxicity in rat hippocampus by suppressing ibotenic acid induced pro-apoptosis. Furthermore, Western blott of hippocampal specimens revealed that icariin up-regulated the expression of calbindin-D28k protein following ibotenic acid administration. Additionally, icariin inhibited mitogen-activated protein kinase (MAPK) family phosphorylation and nuclear factor kappa B (NF-κB) signaling, implicating the MAPK signaling and NF-κB signaling pathways were involved in the mechanism underlying icariin-mediated neuroprotection against ibotenic acid-induced excitotoxicity. These data suggested that icariin could be a potential agent for treatment of excitotoxicity-related diseases, including AD.

Keywords: Alzheimer’s disease; Excitotoxicity; Hippocampus; Ibotenic acid; Icariin; Rat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Alzheimer Disease / prevention & control
  • Animals
  • Apoptosis / drug effects*
  • Calbindins / metabolism
  • Drugs, Chinese Herbal / administration & dosage
  • Epimedium
  • Excitatory Amino Acid Agonists / administration & dosage
  • Flavonoids / administration & dosage*
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Hippocampus / pathology*
  • Ibotenic Acid / administration & dosage
  • Infusions, Intraventricular
  • MAP Kinase Signaling System / drug effects
  • Male
  • NF-kappa B / metabolism
  • Neurons / drug effects
  • Neurons / pathology
  • Neuroprotective Agents / administration & dosage*
  • Rats
  • Rats, Sprague-Dawley
  • Spatial Learning / drug effects
  • Spatial Memory / drug effects

Substances

  • Calbindins
  • Drugs, Chinese Herbal
  • Excitatory Amino Acid Agonists
  • Flavonoids
  • NF-kappa B
  • Neuroprotective Agents
  • Ibotenic Acid
  • icariin