The effect of Curcuma xanthorrhiza extract on the cholinergic system: 5-[123I]iodo-A-85380 micro-SPECT and in vivo microdialysis studies

243 Objectives Curcuma xanthorrhiza is a native plant, which has been proposed to have cholinergic properties in vitro. The aim of this study was to investigate the effects of Curcuma xanthorrhiza extract on extracellular acetylcholine (ACh) levels and α4β2 nicotinic acetylcholine receptors (nAChRs) in the rat brain using in vivo microdialysis and 5-[123I]iodo-A-85380 micro-SPECT, respectively. Methods Extracellular ACh levels were monitored in the thalamus of freely moving rats following administration of Curcuma xanthorrhiza extract (100 mg/kg, i.p.) using in vivo microdialysis and LC-MS/MS. 5-[123I]Iodo-A-85380 micro-SPECT scans were performed in another set of rats 30 min after administration of Curcuma xanthorrhiza extract (100 mg/kg, i.p.) or vehicle alone. 5-[123I]Iodo-A-85380 binding to nAChRs in the thalamus was estimated using the specific-to-nonspecific binding ratio, calculated as (thalamic-cerebellar)/cerebellar radioactivity. Results Administration of Curcuma xanthorrhiza extract elicited an 89.3 ± 34.7% increase in thalamic extracellular ACh over baseline level at the peak time of 30 min after injection (P Conclusions The results of the present study suggest that Curcuma xanthorrhiza extract exerts its effect on the cholinergic system by increasing extracellular ACh levels and by binding to α4β2 neuronal nAChRs. Alternatively, Curcuma xanthorrhiza extract-induced increase in extracellular ACh may cause a reduction in nAChR availability. These preclinical data raise the possibility that Curcuma xanthorrhiza extract, by enhancing cholinergic neurotransmission, may prove to be a useful therapeutic agent for neuropsychological disorders associated with cholinergic deficit.