Modulation of GABAA receptors by valerian extracts is related to the content of valerenic acid.
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 alpha 1, beta 2 and gamma 2S 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 I (GABA) enhancement. In conclusion, our data show that the extent of GABAA receptor modulation by Valerian extracts is related to the content of valerenic acid.
Trauner
Gabriele
G
Department of Pharmacognosy, University of Vienna, Vienna, Austria.
Khom
Sophia
S
Baburin
Igor
I
Benedek
Birgit
B
Hering
Steffen
S
Kopp
Brigitte
B
D000818:Animals; D018118:Chloride Channels / Q000187:drug effects; D005260:Female; D018757:GABA Modulators / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007192:Indenes / Q000737:chemistry; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D018517:Plant Roots; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D012717:Sesquiterpenes / Q000737:chemistry; D014632:Valerian; D014982:Xenopus laevis
D018118:Chloride Channels; D018757:GABA Modulators; D007192:Indenes; D010936:Plant Extracts; D011963:Receptors, GABA-A; D012717:Sesquiterpenes; C037133:valerenic acid