title: Moderate concentrations of 4-O-methylhonokiol potentiate GABAA receptor currents stronger than honokiol.
abstract: BACKGROUND
  Magnolia bark preparations from Magnolia officinalis of Asian medicinal systems are known for their muscle relaxant effect and anticonvulsant activity. These CNS related effects are ascribed to the presence of the biphenyl-type neolignans honokiol and magnolol that exert a potentiating effect on GABAA receptors. 4-O-methylhonokiol isolated from seeds of the North-American M. grandiflora was compared to honokiol for its activity to potentiate GABAA receptors and its GABAA receptor subtype-specificity was established.
  
  
  METHODS
  Different recombinant GABAA receptors were functionally expressed in Xenopus oocytes and electrophysiological techniques were used determine to their modulation by 4-O-methylhonokiol.
  
  
  RESULTS
  3μM 4-O-methylhonokiol is shown here to potentiate responses of the α₁β₂γ₂ GABAA receptor about 20-fold stronger than the same concentration of honokiol. In the present study potentiation by 4-O-methylhonokiol is also detailed for 12 GABAA receptor subtypes to assess GABAA receptor subunits that are responsible for the potentiating effect.
  
  
  CONCLUSIONS
  The much higher potentiation of GABAA receptors at identical concentrations of 4-O-methylhonokiol as compared to honokiol parallels previous observations made in other systems of potentiated pharmacological activity of 4-O-methylhonokiol over honokiol.
  
  
  CONCLUSIONS
  The results point to the use of 4-O-methylhonokiol as a lead for GABAA receptor potentiation and corroborate the use of M. grandiflora seeds against convulsions in Mexican folk medicine.
authors: Institute of Biochemistry and Molecular Medicine, University of Bern, Bühlstr. 28, CH-3012 Bern, Switzerland.
authors: Roland
authors: R
authors: Baur
authors: Institute of Pharmaceutical Sciences, Department of Pharmacognosy, Karl-Franzens-University, Universitätsplatz 4, 8010 Graz, Austria. Electronic address: wolfgang.schuehly@uni-graz.at.
authors: Wolfgang
authors: W
authors: Schuehly
authors: Institute of Biochemistry and Molecular Medicine, University of Bern, Bühlstr. 28, CH-3012 Bern, Switzerland.
authors: Erwin
authors: E
authors: Sigel
mesh_terms: D000818:Animals; D001713:Biphenyl Compounds / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D058785:GABA-A Receptor Agonists / Q000737:chemistry / Q000494:pharmacology*; D005765:Gastrointestinal Agents / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D017705:Lignans / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D031566:Magnolia / Q000737:chemistry; D008564:Membrane Potentials / Q000187:drug effects*; D024301:Plant Bark / Q000737:chemistry; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D001713:Biphenyl Compounds; D058785:GABA-A Receptor Agonists; D005765:Gastrointestinal Agents; D017705:Lignans; D011963:Receptors, GABA-A; C542058:4-O-methylhonokiol; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols
keywords: 4-O-Methylhonokiol; GABA (γ-aminobutyric acid); GABA(A) receptors; Honokiol