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

摘要

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 alpha (1), beta (2) and gamma (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. AVA:acetoxyvalerenic acid CNS:central nervous system EA:crude ethyl acetate extract EtOAc:ethyl acetate extract GABA:gamma-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.