Enhancement of pentobarbital-induced sleep by apigenin through chloride ion channel activation

Arch Pharm Res. 2012 Feb;35(2):367-73. doi: 10.1007/s12272-012-0218-4. Epub 2012 Feb 28.


This experiment was performed to investigate whether apigenin has hypnotic effects and/or enhances pentobarbital-induced sleep behaviors through the GABAergic systems. Apigenin prolonged sleep time induced by pentobarbital similar to muscimol, a GABA(A) receptors agonist. Apigenin also increased sleep rate and sleep time in the combined administration with pentobarbital at the sub-hypnotic dosage, and showed synergic effects with muscimol in potentiating sleep onset and enhancing sleep time induced by pentobarbital. In addition, both of apigeinin and pentobarbital increased chloride influx in primary cultured cerebellar granule cells. Apigenin increased glutamate decarboxylase (GAD) and had no effect on the expression of GABA(A) receptor α-, β-, γ-subunits in n hippocampus of mouse brain, showing different expression of subunits from pentobarbital treatment group. In conclusion, it is suggested that apigenin augments pentobarbital-induced sleep behaviors through chloride ion channel activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apigenin / isolation & purification
  • Apigenin / pharmacology*
  • Cerebellum / drug effects*
  • Cerebellum / metabolism
  • Chloride Channel Agonists*
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Glutamate Decarboxylase / biosynthesis
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hypnotics and Sedatives / agonists*
  • Hypnotics and Sedatives / pharmacology*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Muscimol / agonists
  • Muscimol / pharmacology
  • Pentobarbital / agonists*
  • Pentobarbital / pharmacology
  • Primary Cell Culture
  • Rats
  • Receptors, GABA-A / biosynthesis
  • Sleep / drug effects*


  • Chloride Channel Agonists
  • Hypnotics and Sedatives
  • Receptors, GABA-A
  • Muscimol
  • Apigenin
  • Glutamate Decarboxylase
  • Pentobarbital