title: HPLC-based activity profiling for GABAA receptor modulators in Adenocarpus cincinnatus.
abstract: In a two-microelectrode voltage clamp assay with Xenopus laevis oocytes, a dichloromethane extract of Adenocarpus cincinnatus roots and tubers (Leguminosae) enhanced the GABA-induced chloride current (IGABA) through receptors of the subtype α1β2γ2s by 126.5 ± 25.1% when tested at 100 μg/mL. By means of HPLC-based activity profiling, 15 flavonoid and isoflavonoid derivatives, including eight new compounds, were identified in the active fractions of the extract. Isoflavone 11 and pterocarpans 2 and 8 showed promising activity in the oocyte assay, with EC50 values between 2.8 ± 1.4 and 18.8 ± 2.3 μM. Maximal potentiation of IGABA ranged between 490% and 640%. This is the first report of pterocarpans as GABAA receptor modulators.
authors.affiliation: Division of Pharmaceutical Biology, University of Basel , Klingelbergstrasse 50, 4056 Basel, Switzerland.
authors.forename: Diana C
authors.initials: DC
authors.lastname: Rueda
authors.forename: Maria
authors.initials: M
authors.lastname: De Mieri
authors.forename: Steffen
authors.initials: S
authors.lastname: Hering
authors.forename: Matthias
authors.initials: M
authors.lastname: Hamburger
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003975:Diazepam / Q000494:pharmacology; D007887:Fabaceae / Q000737:chemistry*; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D007529:Isoflavones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D015394:Molecular Structure; D009018:Morocco; D019906:Nuclear Magnetic Resonance, Biomolecular; D009865:Oocytes / Q000378:metabolism; D018517:Plant Roots / Q000737:chemistry; D035281:Plant Tubers / Q000737:chemistry; D011963:Receptors, GABA-A / Q000378:metabolism*; D014982:Xenopus laevis / Q000254:growth & development
chemical_list: D005419:Flavonoids; D007529:Isoflavones; D011963:Receptors, GABA-A; D003975:Diazepam