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Identification and characterization of GABA(A) receptor modulatory diterpenes from Biota orientalis that decrease

Janine Zaugg1, Sophia Khom, Daniela Eigenmann

  • 1Division of Pharmaceutical Biology, University of Basel , Klingelbergstrasse 50, 4056 Basel, Switzerland.

Journal of Natural Products
|July 29, 2011
PubMed
Summary

Biota orientalis leaf extract potentiated GABA(A) receptors, with isopimaric acid and sandaracopimaric acid identified as key active compounds. Sandaracopimaric acid showed higher potency and reduced mouse locomotor activity.

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Area of Science:

  • Pharmacology
  • Neuroscience
  • Natural Products Chemistry

Background:

  • Biota orientalis (Thuja orientalis) is a traditional medicinal plant.
  • GABA(A) receptors are crucial inhibitory neurotransmitter receptors in the central nervous system.
  • Understanding plant-derived modulators of GABA(A) receptors is important for developing new therapeutics.

Purpose of the Study:

  • To investigate the effects of Biota orientalis leaf extract on GABA(A) receptors.
  • To identify the active compounds responsible for the observed activity.
  • To evaluate the subtype selectivity and in vivo effects of the identified compounds.

Main Methods:

  • Two-microelectrode voltage clamp electrophysiology in Xenopus laevis oocytes expressing specific GABA(A) receptor subtypes.
  • High-performance liquid chromatography (HPLC)-based activity profiling for compound identification.
  • In vivo open field tests in mice to assess locomotor activity and anxiolytic-like effects.

Main Results:

  • An ethyl acetate extract of Biota orientalis potentiated GABA-induced currents by 92.6% at 100 μg/mL.
  • Isopimaric acid and sandaracopimaric acid were identified as the primary active constituents.
  • Sandaracopimaric acid demonstrated significantly higher potency than isopimaric acid across several GABA(A) receptor subtypes, particularly α₁β₁γ(2S), α₂β₂γ(2S), and α₅β₂γ(2S).

Conclusions:

  • Biota orientalis leaves contain compounds, notably sandaracopimaric acid, that modulate GABA(A) receptor activity.
  • Sandaracopimaric acid exhibits potent activity at specific GABA(A) receptor subtypes and reduces locomotor activity in mice.
  • These findings highlight the potential of Biota orientalis constituents as modulators of GABAergic neurotransmission.