title: Anxiolytic-like effects of 4-O-methylhonokiol isolated from Magnolia officinalis through enhancement of GABAergic transmission and chloride influx.
abstract: 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.
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Korea.
authors.forename: Huishan
authors.initials: H
authors.lastname: Han
authors.forename: Jae Kyung
authors.initials: JK
authors.lastname: Jung
authors.forename: Sang Bae
authors.initials: SB
authors.lastname: Han
authors.forename: Sang Yoon
authors.initials: SY
authors.lastname: Nam
authors.forename: Ki Wan
authors.initials: KW
authors.lastname: Oh
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage*; D001007:Anxiety / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D001692:Biological Transport / Q000187:drug effects / Q000941:ethics; D001713:Biphenyl Compounds / Q000008:administration & dosage*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D017705:Lignans / Q000008:administration & dosage*; D031566:Magnolia / Q000737:chemistry*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D010936:Plant Extracts / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: C542058:4-O-methylhonokiol; D014151:Anti-Anxiety Agents; D001713:Biphenyl Compounds; D002712:Chlorides; D017705:Lignans; D010936:Plant Extracts; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid