HPLC-based activity profiling for GABAA receptor modulators in Adenocarpus cincinnatus

J Nat Prod. 2014 Mar 28;77(3):640-9. doi: 10.1021/np500016z. Epub 2014 Feb 26.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatography, High Pressure Liquid
  • Diazepam / pharmacology
  • Fabaceae / chemistry*
  • Flavonoids / chemistry
  • Flavonoids / isolation & purification*
  • Flavonoids / pharmacology*
  • Isoflavones / chemistry
  • Isoflavones / isolation & purification*
  • Isoflavones / pharmacology*
  • Molecular Structure
  • Morocco
  • Nuclear Magnetic Resonance, Biomolecular
  • Oocytes / metabolism
  • Plant Roots / chemistry
  • Plant Tubers / chemistry
  • Receptors, GABA-A / metabolism*
  • Xenopus laevis / growth & development

Substances

  • Flavonoids
  • Isoflavones
  • Receptors, GABA-A
  • Diazepam