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ANESTHETIC PHARMACOLOGY

The Gamma-Aminobutyric Acidergic Effects of Valerian and Valerenic Acid on Rat Brainstem Neuronal Activity

Chun-Su Yuan, MD PhD^*,,, Sangeeta Mehendale, MD PhD^*,, Yingping Xiao, PhD, Han H. Aung, MD^*,, Jing-Tian Xie, MD, and Michael K. Ang-Lee, MD^*

*Department of Anesthesia & Critical Care, Tang Center for Herbal Medicine Research, and Committee on Clinical Pharmacology and Pharmacogenomics, Pritzker School of Medicine, University of Chicago, Chicago, Illinois

Address correspondence and reprint requests to Chun-Su Yuan, MD, PhD, Department of Anesthesia & Critical Care, Pritzker School of Medicine, The University of Chicago, 5841 S. Maryland Ave., MC 4028, Chicago, IL 60637. Address e-mail to cyuan{at}airway.uchicago.edu

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 µM produced a 38.9% ± 3.0% (mean ± SE) inhibition compared with control values (P < 0.01; 50% inhibitory concentration [IC₅₀], 2.0 ± 0.1 µM). This effect was antagonized by bicuculline (10 µM), 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 µg/mL, whereas 100 µM valerenic acid induced a 22.2% ± 3.4% inhibition with an IC₅₀ of 23 ± 2.6 µM (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.

IMPLICATIONS: Valerian is an herb used in treating anxiety and insomnia. We observed that the valerian effects are mediated through brain gamma-aminobutyric acid (GABA) receptors in a rat brainstem preparation. Thus, valerian may potentiate the effects of anesthetics that act on GABA receptors, and presurgical valerian use may cause a valerian-anesthetic interaction.

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999