Protective effect of hispidulin on kainic acid-induced seizures and neurotoxicity in rats

Eur J Pharmacol. 2015 May 15:755:6-15. doi: 10.1016/j.ejphar.2015.02.041. Epub 2015 Mar 5.

Abstract

Hispidulin is a flavonoid compound which is an active ingredient in a number of traditional Chinese medicinal herbs, and it has been reported to inhibit glutamate release. The purpose of this study was to investigate whether hispidulin protects against seizures induced by kainic acid, a glutamate analog with excitotoxic properties. The results indicated that intraperitoneally administering hispidulin (10 or 50mg/kg) to rats 30 min before intraperitoneally injecting kainic acid (15 mg/kg) increased seizure latency and decreased seizure score. In addition, hispidulin substantially attenuated kainic acid-induced hippocampal neuronal cell death, and this protective effect was accompanied by the suppression of microglial activation and the production of proinflammatory cytokines such as interleukin-1β, interleukin-6, and tumor necrosis factor-α in the hippocampus. Moreover, hispidulin reduced kainic acid-induced c-Fos expression and the activation of mitogen-activated protein kinases in the hippocampus. These data suggest that hispidulin has considerable antiepileptic, neuroprotective, and antiinflammatory effects on kainic acid-induced seizures in rats.

Keywords: Anti-inflammation; Antiepileptic effect; Hippocampus; Hispidulin (PubChem CID:5281628); Kainic acid (PubChem CID:10255); Neuroprotection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Anticonvulsants / pharmacology
  • Anticonvulsants / therapeutic use*
  • CA3 Region, Hippocampal / drug effects
  • CA3 Region, Hippocampal / metabolism
  • CA3 Region, Hippocampal / pathology
  • Cell Death / drug effects
  • Cytokines / genetics
  • Flavones / pharmacology
  • Flavones / therapeutic use*
  • Kainic Acid
  • Male
  • Microglia / drug effects
  • Neurons / drug effects
  • Neurons / pathology
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • RNA, Messenger / metabolism
  • Rats, Sprague-Dawley
  • Seizures / chemically induced
  • Seizures / drug therapy*
  • Seizures / metabolism
  • Seizures / pathology

Substances

  • Anti-Inflammatory Agents
  • Anticonvulsants
  • Cytokines
  • Flavones
  • Neuroprotective Agents
  • RNA, Messenger
  • hispidulin
  • Kainic Acid