NMDA recepter-mediated neuroprotection by essential oils from the rhizomesof Acorus gramineus

Acori graminei Rhizoma (AGR) is shown to exhibit a number of pharmacologica l actions including sedation and anticonvulsive action. To further characte rize its actions in the CNS, the present study evaluated the effects of ess ential oils (EO) from AGR on the excitotoxic neuronal cell death induced in primary rat cortical cell cultures. EO inhibited the glutamate-induced exc itotoxicity in a concentration-dependent manner, with the IC50 of 0.241mg/m l, EO exerted more potent neuroprotection against the toxicity induced by N MDA (IC50 = 0.139 mg/ml). In contrast, the AMPA-induced toxicity was not in hibited by EO. Receptor-ligand binding studies were performed to investigat e the neuroprotective action mechanism. EO dramatically inhibited the speci fic bindings of a use-dependent NMDA receptor-ion channel blocker [H-3]MK-8 01, indicating an NMDA receptor antagonist-like action. However, the bindin gs of [H-3]MDL 105,519, a ligand selective for the glycine binding site of NMDA receptor, were not considerably inhibited. These results demonstrated that EO extracted from AGR exhibited neuroprotective effects on cultured co rtical neurons through the blockade of NMDA receptor activity, and that the glycine binding site appeared not to be the major site of action. (C) 2001 Elsevier Science Inc. All rights reserved.