Planta Med 2008; 74(1): 19-24
DOI: 10.1055/s-2007-993761
Pharmacology
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Modulation of GABAA Receptors by Valerian Extracts is Related to the Content of Valerenic Acid

Gabriele Trauner1 , Sophia Khom2 , Igor Baburin2 , Birgit Benedek1 , Steffen Hering2 , Brigitte Kopp1
  • 1Department of Pharmacognosy, University of Vienna, Vienna, Austria
  • 2Department of Pharmacology and Toxicology, University of Vienna, Vienna, Austria
Further Information

Publication History

Received: June 20, 2007 Revised: October 30, 2007

Accepted: November 2, 2007

Publication Date:
19 December 2007 (online)

Abstract

Valeriana officinalis L. is a traditionally used sleep remedy, however, the mechanism of action and the substances responsible for its sedative and sleep-enhancing properties are not fully understood. As we previously identified valerenic acid as a subunit-specific allosteric modulator of GABAA receptors, we now investigated the relation between modulation of GABAA receptors by Valerian extracts of different polarity and the content of sesquiterpenic acids (valerenic acid, acetoxyvalerenic acid). All extracts were analysed by HPLC concerning the content of sesquiterpenic acids. GABAA receptors composed of α1, β2 and γ2S subunits were expressed in Xenopus laevis oocytes and the modulation of chloride currents through GABAA receptors (IGABA) by Valerian extracts was investigated using the two-microelectrode voltage clamp technique. Apolar extracts induced a significant enhancement of IGABA, whereas polar extracts showed no effect. These results were confirmed by fractionating a highly active ethyl acetate extract: again fractions with high contents of valerenic acid exhibited strong receptor activation. In addition, removal of sesquiterpenic acids from the ethyl acetate extract led to a loss of IGABA enhancement. In conclusion, our data show that the extent of GABAA receptor modulation by Valerian extracts is related to the content of valerenic acid.

Abbreviations

AVA:acetoxyvalerenic acid

CNS:central nervous system

EA:crude ethyl acetate extract

EtOAc:ethyl acetate extract

GABA:γ-amino butyric acid

GABAA receptor:GABA activated type A receptor

H2O:distilled water extract

HVA:hydroxyvalerenic acid

IGABA:GABA-induced chloride current through GABAA receptors

MeOH:methanol extract

PE:petroleum ether extract

RV:reservoir volumina

TLC:thin layer chroamtography

VA:valerenic acid

VLC:vacuum liquid chromatography

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Prof. Brigitte Kopp

Department of Pharmacognosy

University of Vienna

Althansstrasse 14

1090 Wien

Austria

Phone: +43-1-4277-55255

Fax: +43-1-4277-55256

Email: Brigitte.kopp@univie.ac.at

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