Magnolol, a major bioactive constituent of the bark of Magnolia officinalis, induces sleep via the benzodiazepine site of GABA(A) receptor in mice

Neuropharmacology. 2012 Nov;63(6):1191-9. doi: 10.1016/j.neuropharm.2012.06.031. Epub 2012 Jul 4.


Magnolol (6,6',7,12-tetramethoxy-2,2'-dimethyl-1-beta-berbaman, C(18)H(18)O(2)), an active ingredient of the bark of Magnolia officinalis, has been reported to exert potent anti-epileptic effects via the GABA(A) receptor. The receptor also mediates sleep in humans and animals. The aim of this study was to determine whether magnolol could modulate sleep behaviors by recording EEG and electromyogram in mice. The results showed that magnolol administered i.p. at a dose of 5 or 25 mg/kg could significantly shorten the sleep latency, increase the amount of non-rapid eye movement (non-REM, NREM) and rapid eye movement (REM) sleep for 3 h after administration with an increase in the number of NREM and REM sleep episodes. Magnolol at doses of 5 and 25 mg/kg increased the number of bouts of wakefulness but decreased their duration. On the other hand, magnolol increased the number of state transitions from wakefulness to NREM sleep and subsequently from NREM sleep to wakefulness. Immunohistochemical study showed that magnolol increased c-Fos expression in the neurons of ventrolateral preoptic area, a sleep center in the anterior hypothalamus, and decreased c-Fos expression in the arousal tuberomammillary nucleus, which was located in the caudolateral hypothalamus. The sleep-promoting effects and changes in c-Fos induced by magnolol were reversed by flumazenil, an antagonist at the benzodiazepine site of the GABA(A) receptor. These results indicate that magnolol increased NREM and REM sleep via the GABA(A) receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arousal / drug effects
  • Biphenyl Compounds / chemistry
  • Biphenyl Compounds / pharmacology*
  • Diazepam / pharmacology
  • Drug Interactions
  • Electroencephalography
  • Electromyography
  • Flumazenil / pharmacology
  • GABA Modulators*
  • Gene Expression / drug effects
  • Genes, fos / drug effects
  • Hypothalamic Area, Lateral / drug effects
  • Hypothalamic Area, Lateral / physiology
  • Immunohistochemistry
  • Lignans / chemistry
  • Lignans / pharmacology*
  • Magnolia / chemistry*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Plant Bark / chemistry
  • Polysomnography
  • Preoptic Area / drug effects
  • Preoptic Area / metabolism
  • Receptors, GABA-A / drug effects*
  • Sleep / drug effects*
  • Sleep, REM / drug effects


  • Biphenyl Compounds
  • GABA Modulators
  • Lignans
  • Receptors, GABA-A
  • magnolol
  • Flumazenil
  • Diazepam