Identification of dehydroabietc acid from Boswellia thurifera resin as a positive GABAA receptor modulator

Fitoterapia. 2014 Dec:99:28-34. doi: 10.1016/j.fitote.2014.09.002. Epub 2014 Sep 6.

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.

Keywords: Abietane diterpenes; Boswellia thurifera; Dehydroabietic acid; GABA(A) receptor modulators; HPLC-based activity profiling; Olibanum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abietanes / chemistry*
  • Abietanes / isolation & purification
  • Animals
  • Boswellia / chemistry*
  • Diterpenes / chemistry
  • Diterpenes / isolation & purification
  • GABA-A Receptor Agonists / chemistry
  • GABA-A Receptor Agonists / isolation & purification
  • Molecular Structure
  • Oocytes
  • Receptors, GABA-A / drug effects*
  • Resins, Plant / chemistry*
  • Xenopus

Substances

  • Abietanes
  • Diterpenes
  • GABA-A Receptor Agonists
  • Receptors, GABA-A
  • Resins, Plant
  • incensole acetate
  • abietic acid