Phytochemical profiling of Curcuma kwangsiensis rhizome extract, and identification of labdane diterpenoids as positive GABAA receptor modulators

An ethyl acetate extract of Curcuma kwangsiensis S.G. Lee & C.F. Liang (Zingiberaceae) rhizomes (100 mu g/ml) enhanced the GABA-induced chloride current (I-GABA) through GABA(A) receptors of the alpha(1)beta(2)gamma(2s) subtype by 79.0 +/- 7.0%. Potentiation of I-GABA was measured using the two-microelectrode voltage-clamp technique and Xenopus laevis oocytes. HPLC-based activity profiling of the crude extract led to the identification of 11 structurally related labdane diterpenoids, including four new compounds. Structure elucidation was achieved by comprehensive analysis of on-line (LC-PDA-ESI-TOF-MS) and off-line (microprobe 1D and 2D NMR) spectroscopic data. The absolute configuration of the compounds was established by comparison of experimental and calculated ECD spectra. Labdane diterpenes represent a new class of plant secondary metabolites eliciting positive GABA(A) receptor modulation. The highest efficiency was observed for zerumin A (maximum potentiation of I-GABA by 309.4 +/- 35.6%, and EC50, of 24.9 +/- 8.8 mu M). (C) 2013 Elsevier Ltd. All rights reserved.