HPLC-based activity profiling of Angelica pubescens roots for new positive GABA A receptor modulators in Xenopus oocytes

• Published in: Fitoterapia Vol. 82; no. 3; pp. 434 - 440
• Main Authors: Zaugg, Janine, Eickmeier, Eva, Rueda, Diana C., Hering, Steffen, Hamburger, Matthias
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01-04-2011
• Subjects: Angelica pubescens; Coumarins; GABA A receptor; HPLC-based activity profiling; Two-microelectrode voltage clamp; Xenopus oocytes; Xenopus oocytes; Angelica pubescens; GABA A receptor; I GABA; GABA; Coumarins; Two-microelectrode voltage clamp; GABA EC 5–10; HPLC-based activity profiling; TCM
• ISSN: 0367-326X
• DOI: 10.1016/j.fitote.2010.12.001

A petroleum ether extract of the traditional Chinese herbal drug
Duhuo (roots of
Angelica pubescens Maxim. f.
biserrata Shan et Yuan), showed significant activity in a functional two-microelectrode voltage clamp assay with
Xenopus oocytes which expressed recombinant γ-aminobutyric acid type A (GABA
A) receptors of the subtype α
1β
2γ
2S. HPLC-based activity profiling of the active extract revealed six compounds responsible for the GABA
A receptor modulating activity. They were identified by microprobe NMR and high resolution mass spectrometry as columbianetin acetate (
1), imperatorin (
3), cnidilin (
4), osthol (
5), and columbianedin (
6). In concentration-dependent experiments, osthol and cnidilin showed the highest potentiation of the GABA induced chloride current (273.6%
±
39.4% and 204.5%
±
33.2%, respectively at 300
μM). Bisabolangelone (
2) only showed minor activity at the GABA
A receptor. The example demonstrates that HPLC-based activity profiling is a simple and efficient method to rapidly identify GABA
A receptor modulators in a bioactive plant extract.
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HPLC-based activity profiling of
Angelica pubescens roots enabled the identification of coumarins which modulate GABA
A receptors of the α
1β
2γ
2S subtype in a two-microelectrode voltage clamp assay with
Xenopus oocytes.