The gamma-aminobutyric acidergic effects of valerian and valerenic acid on rat brainstem neuronal activity

Valerian is a medicinal herb that produces anxiolytic and sedative effects. It was suggested that valerian acts via gamma-aminobutyric acid (GABA)ergic mechanisms. Previous studies showed binding of valerian extract to GABA receptors, but the functional effect of the binding has not been demonstrated. In this study we evaluated the GABAergic effect of valerian extract and one of its major constituents, valerenic acid, on brainstem neuronal activity in an in vitro neonatal rat brainstem preparation. We first observed that muscimol, a GABA(A) receptor agonist, decreased the firing rate in most brainstem neurons in a concentration-related fashion; 30 muM produced a 38.9% +/- 3.0% (mean +/- SE) inhibition compared with control values (P < 0.01; 50% inhibitory concentration [IC50 ], 2.0 +/- 0.1 muM). This effect was antagonized by bicuculline (10 muM), a GABA(A) antagonist. Then we showed that valerian extract 3 mg/mL induced a 29.6% +/- 5.1% inhibition with an IC50 of 240 +/- 18.7 mug/mL, whereas 100 muM valerenic acid induced a 22.2% +/- 3.4% inhibition with an IC50 of 23 +/- 2.6 muM (both P < 0.01). Bicuculline antagonized the inhibitory effects of both the valerian extract and valerenic acid. In addition, pretreatment with valerian extract or valerenic acid decreased the brainstem inhibitory effects produced by muscimol (both P < 0.05), suggesting that these compounds play an important role in the regulation of GABAergic activity. Data from this study suggest that the pharmacological effects of valerian extract and valerenic acid are mediated through modulation of GABA(A) receptor function. Thus, valerian may potentiate the sedative effects of anesthetics and other medications that act on GABA receptors, and presurgical valerian use may cause a valerian-anesthetic interaction.