Curcumol from Rhizoma Curcumae suppresses epileptic seizure by facilitation of GABA(A) receptors

Abstract

Rhizoma Curcumae is a common Chinese dietary spice used in South Asia and China for thousands of years. As the main extract, Rhizoma Curcumae oil has attracted a great interest due to its newly raised therapeutic activities including its pharmacological effects upon central nervous system such as neuroprotection, cognitive enhancement, and anti-seizure efficacy; however the molecular mechanisms and the target identification remain to be established. Here we characterize an inhibitory effect of curcumol, a major bioactive component of Rhizoma Curcumae oil, on the excitability of hippocampal neurons in culture, the basal locomotor activity of freely moving animals, and the chemically induced seizure activity in vivo. Electrophysiological recording showed that acute application of curcumol significantly facilitated the γ-aminobutyric acid (GABA)-activated current in cultured mouse hippocampal neurons and in human embryonic kidney cells expressing α1- or α5-containing A type GABA (GABAA) receptors in a concentration-dependent manner. Measurement of tonic and miniature inhibitory postsynaptic GABAergic currents in hippocampal slices indicated that curcumol enhanced both forms of inhibition. In both pentylenetetrazole and kainate seizure models, curcumol suppressed epileptic activity in mice by prolonging the latency to clonic and tonic seizures and reducing the mortality as well as the susceptibility to seizure, presumably by facilitating the activation of GABAA receptors. Taken together, our results identified curcumol as a novel anti-seizure agent which inhibited neuronal excitability through enhancing GABAergic inhibition.