title: HPLC-based activity profiling of Angelica pubescens roots for new positive GABAA receptor modulators in Xenopus oocytes.
abstract: A petroleum ether extract of the traditional Chinese herbal drug Duhuo (roots of Angelica pubescens Maxim. f. biserrata Shan et Yuan), showed significant activity in a functional two-microelectrode voltage clamp assay with Xenopus oocytes which expressed recombinant γ-aminobutyric acid type A (GABA(A)) receptors of the subtype α(1)β(2)γ(2S). HPLC-based activity profiling of the active extract revealed six compounds responsible for the GABA(A) receptor modulating activity. They were identified by microprobe NMR and high resolution mass spectrometry as columbianetin acetate (1), imperatorin (3), cnidilin (4), osthol (5), and columbianedin (6). In concentration-dependent experiments, osthol and cnidilin showed the highest potentiation of the GABA induced chloride current (273.6%±39.4% and 204.5%±33.2%, respectively at 300 μM). Bisabolangelone (2) only showed minor activity at the GABA(A) receptor. The example demonstrates that HPLC-based activity profiling is a simple and efficient method to rapidly identify GABA(A) receptor modulators in a bioactive plant extract.
authors.affiliation: Institute of Pharmaceutical Biology, University of Basel, Basel, Switzerland.
authors.forename: Janine
authors.initials: J
authors.lastname: Zaugg
authors.forename: Eva
authors.initials: E
authors.lastname: Eickmeier
authors.forename: Diana C
authors.initials: DC
authors.lastname: Rueda
authors.forename: Steffen
authors.initials: S
authors.lastname: Hering
authors.forename: Matthias
authors.initials: M
authors.lastname: Hamburger
mesh_terms: D029969:Angelica / Q000737:chemistry*; D000818:Animals; D002712:Chlorides / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003374:Coumarins / Q000032:analysis / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018755:GABA Agonists / Q000494:pharmacology*; D006575:Heterocyclic Compounds, 3-Ring / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D009865:Oocytes / Q000187:drug effects; D018517:Plant Roots; D011963:Receptors, GABA-A / Q000378:metabolism*; D014981:Xenopus
chemical_list: D002712:Chlorides; D003374:Coumarins; D004365:Drugs, Chinese Herbal; D018755:GABA Agonists; D006575:Heterocyclic Compounds, 3-Ring; D011963:Receptors, GABA-A; C560695:cnidilin; C046627:osthol