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 pharmacolo gical actions in the central nervous system. The effects of the methanol ex tract of AGR on excitotoxic neuronal death were evaluated in the present st udy using cultured rat cortical neurons. Based on the phase-contrast micros copic examinations of cultures and lactate dehydrogenase activities measure d in the culture media, the glutamate-induced excitotoxicity was significan tly 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 [H-3]MDL 105,519 for the specific binding to the glycine site of the NMDA receptor with the IC50 value of 164 .7 mug/ml. Modulation of the NMDA receptor activity by the extract was dete rmined using [H-3]MK-801 binding studies. The reduction of the binding in t he presence of the extract indicated the receptor inactivation by AGR. Thes e results demonstrated that the methanol extract of AGR exhibited protectiv e action against excitotoxic neuronal death, and that the neuroprotective a ction was primarily due to the blockade of NMDA receptor function by the in teraction with the glycine binding site of the receptor. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.