Anxiolytic-like effects of 4-O-methylhonokiol isolated from Magnolia officinalis through enhancement of GABAergic transmission and chloride influx

J Med Food. 2011 Jul-Aug;14(7-8):724-31. doi: 10.1089/jmf.2010.1111. Epub 2011 Apr 18.


Abstract This study investigated the anxiolytic-like effects of 4-O-methylhonokiol, a neolignan compound of Magnolia officinalis, by using the experimental paradigms of anxiety and compared the results with those of a known anxiolytic, diazepam. A single treatment with 4-O-methylhonokiol (0.1, 0.2, and 0.5 mg/kg, p.o.) or treatment for 7 days (0.5 mg/kg in drinking water) increased the percentage of time spent in the open arms and the number of open arms entries in the elevated plus-maze test. However, the 4-O-methylhonokiol-increased percentage of time spent in the open arm was abolished by treatment with flumazenil, a benzodiazepine receptor antagonist (10 mg/kg). 4-O-Methylhonokiol also increased the number of head dips in the hole-board test, but decreased locomotor activity. Molecular experiments revealed that the α1-subunit of γ-aminobutyric acid (GABA) type A receptors was overexpressed in the cortex of brains of mice after treatment with 4-O-methylhonokiol for 7 days. In addition, 4-O-methylhonokiol also increased chloride influx in cultured cortical cells. It is concluded that 4-O-methylhonokiol may have anxiolytic-like effects and that these effects may be mediated by GABAergic transmission with the increase of Cl(-) channel opening.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Anxiety Agents / administration & dosage*
  • Anxiety / drug therapy*
  • Anxiety / genetics
  • Anxiety / metabolism
  • Anxiety / physiopathology
  • Biological Transport / drug effects
  • Biological Transport / ethics
  • Biphenyl Compounds / administration & dosage*
  • Brain / drug effects
  • Brain / metabolism
  • Chlorides / metabolism*
  • Disease Models, Animal
  • Humans
  • Lignans / administration & dosage*
  • Magnolia / chemistry*
  • Male
  • Maze Learning / drug effects
  • Mice
  • Mice, Inbred ICR
  • Motor Activity / drug effects
  • Plant Extracts / administration & dosage*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-A / genetics
  • Receptors, GABA-A / metabolism
  • gamma-Aminobutyric Acid / metabolism*


  • 4-O-methylhonokiol
  • Anti-Anxiety Agents
  • Biphenyl Compounds
  • Chlorides
  • Lignans
  • Plant Extracts
  • Receptors, GABA-A
  • gamma-Aminobutyric Acid