HPLC-based activity profiling of Angelica pubescens roots for new positive GABA sub(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: 01-04-2011
• Subjects: Angelica; Xenopus
• 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 gamma -aminobutyric acid type A (GABA sub(A)) receptors of the subtype alpha sub(1) beta sub(2) gamma sub(2)S. HPLC-based activity profiling of the active extract revealed six compounds responsible for the GABA sub(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 mu M). Bisabolangelone ( 2) only showed minor activity at the GABA sub(A) receptor. The example demonstrates that HPLC-based activity profiling is a simple and efficient method to rapidly identify GABA sub(A) receptor modulators in a bioactive plant extract.