Identification of GABAA-modulators obtained from Valeriana officinalis L

Valeriana officinalis L. is used in phytotherapy due to its sedative and sleep enhancing effects. Its application is principally focused on disorders of initiating sleep and problems in sleeping through, states of anxiety as well as depressive moods. Nevertheless, little is known about the mode of action and substances determining the efficacy.

One of the jointly responsible mechanisms of action for sedative substances is stimulation of the GABA_A-receptor. The aim of our study was to identify substances from Valeriana officinalis L. which stimulate the GABA_A-receptor. Isolated frog-oocytes from the genus Xenopus laevis were employed. Centring on heterologously expressed GABA_A-channels, the Two-Electrode Voltage-Clamp (TEVC) mode was used for the measurements [1].

In a first screening of commercial extracts we observed coherence between different polarity and stimulation of the receptor. Apolar extracts revealed high activity, whereas polar extracts showed no effect. All extracts were characterised by HPLC analysis of the sesquiterpene acids according to Pharmacopoeia Europea.

Fractionating a highly potent apolar extract confirmed our first results: Apolar fractions containing high amount of sesquiterpene acids showed strong stimulation. In order to verify correlation between content of sesquiterpene acids and receptor stimulation, valerenic acid and acetoxyvalerenic acid were tested on the GABA_A-receptor. Valerenic acid showed strong stimulation, whereas acetoxyvalerenic acid inhibited the receptor.

In conclusion, one possibility for the mode of action of valerian roots is the stimulation of the GABA_A-receptor, and one of the major compounds, valerenic acid, is not only a marker for standardisation but also a potent activator of the GABA_A-receptor.

Reference: 1. Hering, S. (1998), Pflugers Arch. 436: 303–307.