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 GABA A receptors, we now investigated the relation between modulation of GABA A 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. GABA A receptors composed of α 1 , β 2 and γ 2S subunits were expressed in Xenopus laevis oocytes and the modulation of chloride currents through GABA A receptors (I GABA ) by Valerian extracts was investigated using the two-microelectrode voltage clamp technique. Apolar extracts induced a significant enhancement of I GABA , 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 I GABA enhancement. In conclusion, our data show that the extent of GABA A 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 GABA A receptor:GABA activated type A receptor H 2 O:distilled water extract HVA:hydroxyvalerenic acid I GABA :GABA-induced chloride current through GABA A 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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Trauner et al. (2008) studied this question.