RESEARCH ARTICLE Kavain, the Major Constituent of the Anxiolytic Kava Extract, Potentiates GABAA Receptors: Functional Characteristics and Molecular Mechanism Han Chow Chua1, Emilie T. H. Christensen1,2, Kirsten Hoestgaard-Jensen2, Leonny Y. Hartiadi1, Iqbal Ramzan1, Anders A. Jensen2, Nathan L. Absalom1, Mary Chebib1* 1 Faculty of Pharmacy, The University of Sydney, Sydney, New South Wales, Australia, 2 Department of a11111 Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark *
[email protected] Abstract OPEN ACCESS Extracts of the pepper plant kava (Piper methysticum) are effective in alleviating anxiety in Citation: Chua HC, Christensen ETH, Hoestgaard- Jensen K, Hartiadi LY, Ramzan I, Jensen AA, et al. clinical trials. Despite the long-standing therapeutic interest in kava, the molecular target(s) (2016) Kavain, the Major Constituent of the Anxiolytic of the pharmacologically active constituents, kavalactones have not been established. γ- Kava Extract, Potentiates GABAA Receptors: Aminobutyric acid type A receptors (GABAARs) are assumed to be the in vivo molecular tar- Functional Characteristics and Molecular Mechanism. PLoS ONE 11(6): e0157700. doi:10.1371/journal. get of kavalactones based on data from binding assays, but evidence in support of a direct pone.0157700 interaction between kavalactones and GABAARs is scarce and equivocal. In this study, we Editor: Steven Barnes, Dalhousie University, characterised the functional properties of the major anxiolytic kavalactone, kavain at human CANADA recombinant α1β2, β2γ2L, αxβ2γ2L (x = 1, 2, 3 and 5), α1βxγ2L (x = 1, 2 and 3) and α4β2δ Received: March 24, 2016 GABAARs expressed in Xenopus oocytes using the two-electrode voltage clamp technique.