title: Identification of dehydroabietc acid from Boswellia thurifera resin as a positive GABAA receptor modulator.
abstract: In a two-microelectrode voltage clamp assay with Xenopus laevis oocytes, a petroleum ether extract (100 μg/mL) of the resin of Boswellia thurifera (Burseraceae) potentiated GABA-induced chloride currents (IGABA) through receptors of the subtype α₁β₂γ₂s by 319.8% ± 79.8%. With the aid of HPLC-based activity profiling, three known terpenoids, dehydroabietic acid (1), incensole (2), and AKBA (3), were identified in the active fractions of the extract. Structure elucidation was achieved by means of HR-MS and microprobe 1D/2D NMR spectroscopy. Compound 1 induced significant receptor modulation in the oocyte assay, with a maximal potentiation of IGABA of 397.5% ± 34.0%, and EC₅₀ of 8.7 μM ± 1.3 μM. This is the first report of dehydroabietic acid as a positive GABAA receptor modulator.
authors.affiliation: Division of Pharmaceutical Biology, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland.
authors.forename: Diana C
authors.initials: DC
authors.lastname: Rueda
authors.affiliation: Division of Pharmaceutical Biology, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland.
authors.forename: Melanie
authors.initials: M
authors.lastname: Raith
authors.affiliation: Division of Pharmaceutical Biology, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland.
authors.forename: Maria
authors.initials: M
authors.lastname: De Mieri
authors.affiliation: Institute of Pharmacology and Toxicology, University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria.
authors.forename: Angela
authors.initials: A
authors.lastname: Schöffmann
authors.affiliation: Institute of Pharmacology and Toxicology, University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria.
authors.forename: Steffen
authors.initials: S
authors.lastname: Hering
authors.affiliation: Division of Pharmaceutical Biology, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland. Electronic address: matthias.hamburger@unibas.ch.
authors.forename: Matthias
authors.initials: M
authors.lastname: Hamburger
mesh_terms: D045784:Abietanes / Q000737:chemistry* / Q000302:isolation & purification; D000818:Animals; D029743:Boswellia / Q000737:chemistry*; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification; D058785:GABA-A Receptor Agonists / Q000737:chemistry / Q000302:isolation & purification; D015394:Molecular Structure; D009865:Oocytes; D011963:Receptors, GABA-A / Q000187:drug effects*; D012116:Resins, Plant / Q000737:chemistry*; D014981:Xenopus
chemical_list: D045784:Abietanes; D004224:Diterpenes; D058785:GABA-A Receptor Agonists; D011963:Receptors, GABA-A; D012116:Resins, Plant; C530368:incensole acetate; C023710:abietic acid
keywords: Abietane diterpenes; Boswellia thurifera; Dehydroabietic acid; GABA(A) receptor modulators; HPLC-based activity profiling; Olibanum