Obovatol isolated from Magnolia obovata enhances pentobarbital-induced sleeping time: Possible involvement of GABAA receptors/chloride channel activation

Phytomedicine. 2009 Apr;16(4):308-13. doi: 10.1016/j.phymed.2008.12.007. Epub 2009 Feb 6.

Abstract

This study aimed to investigate the effects of obovatol isolated from Magnolia obovata on pentobarbital-induced sleeping behaviors and to determine whether these effects were mediated by GABA(A) receptors/chloride channel activation, using a western blot technique and Cl(-) sensitive fluorescence probe. GABA(A) receptors subunits expression and chloride influx were investigated in cultured cerebellar granule cells. Obovatol (0.05, 0.1, and 0.2 mg/kg) prolonged the sleeping time induced by pentobarbital (42 mg/kg). In addition, obovatol (20 and 50 microM) significantly increased Cl(-) influx in the primary cultured cerebellar granule cells. Moreover, obovatol increased the expression of GABA(A) receptor alpha-, beta-, and gamma-subunits. However, it had no effect on the abundance of the expression of glutamic acid decarboxylase (GAD), suggesting that obovatol might not activate GAD. These results suggest that obovatol potentiates pentobarbital-induced sleeping time through the GABA(A) receptors/chloride channel activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Biphenyl Compounds / chemistry
  • Biphenyl Compounds / isolation & purification
  • Biphenyl Compounds / pharmacology*
  • Brain / metabolism*
  • Chloride Channels / metabolism*
  • GABA Modulators / pharmacology*
  • Glutamate Decarboxylase / metabolism
  • Magnolia* / chemistry
  • Male
  • Mice
  • Mice, Inbred ICR
  • Neurons / metabolism
  • Pentobarbital / pharmacology
  • Phenyl Ethers / chemistry
  • Phenyl Ethers / isolation & purification
  • Phenyl Ethers / pharmacology*
  • Plant Extracts / pharmacology
  • Plant Leaves
  • Receptors, GABA-A / metabolism*
  • Sleep / drug effects*

Substances

  • Biphenyl Compounds
  • Chloride Channels
  • GABA Modulators
  • Phenyl Ethers
  • Plant Extracts
  • Receptors, GABA-A
  • obovatol
  • Glutamate Decarboxylase
  • glutamate decarboxylase 1
  • glutamate decarboxylase 2
  • Pentobarbital