NMDA recepter-mediated neuroprotection by essential oils from the rhizomes of Acorus gramineus.

Acori graminei Rhizoma (AGR) is shown to exhibit a number of pharmacological actions including sedation and anticonvulsive action. To further characterize its actions in the CNS, the present study evaluated the effects of essential oils (EO) from AGR on the excitotoxic neuronal cell death induced in primary rat cortical cell cultures. EO inhibited the glutamate-induced excitotoxicity in a concentration-dependent manner, with the IC50 of 0.241 mg/ml. EO exerted more potent neuroprotection against the toxicity induced by NMDA (IC50 = 0.139 mg/ml). In contrast, the AMPA-induced toxicity was not inhibited by EO. Receptor-ligand binding studies were performed to investigate the neuroprotective action mechanism. EO dramatically inhibited the specific bindings of a use-dependent NMDA receptorion channel blocker [3H]MK-801, indicating an NMDA receptor antagonist-like action. However, the bindings of [3H]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 cortical neurons through the blockade of NMDA receptor activity, and that the glycine binding site appeared not to be the major site of action.

Inhibition of excitotoxic neuronal death by methanol extract of Acori graminei rhizoma in cultured rat cortical neurons.

Acori graminei rhizoma (AGR) are reported to exhibit a number of pharmacological actions in the central nervous system. The effects of the methanol extract of AGR on excitotoxic neuronal death were evaluated in the present study using cultured rat cortical neurons. Based on the phase-contrast microscopic examinations of cultures and lactate dehydrogenase activities measured in the culture media, the glutamate-induced excitotoxicity was significantly inhibited by the extract. The inhibitory action of the extract was more potent and selective for the N-methyl-D-aspartate (NMDA) receptor-mediated toxicity. The AGR extract competed with [3H]MDL 105,519 for the specific binding to the glycine site of the NMDA receptor with the IC(50) value of 164.7 microg/ml. Modulation of the NMDA receptor activity by the extract was determined using [3H]MK-801 binding studies. The reduction of the binding in the presence of the extract indicated the receptor inactivation by AGR. These results demonstrated that the methanol extract of AGR exhibited protective action against excitotoxic neuronal death, and that the neuroprotective action was primarily due to the blockade of NMDA receptor function by the interaction with the glycine binding site of the receptor.