title: Protection of cultured rat cortical neurons from excitotoxicity by asarone, a major essential oil component in the rhizomes of Acorus gramineus.
abstract: Previous reports have shown that the methanol extract and the essential oil from Acori graminei Rhizoma (AGR) inhibited excitotoxic neuronal cell death in primary cultured rat cortical cells. In the present study, an active principle was isolated from the methanol extract by biological activity-guided fractionations and identified as asarone. We evaluated neuroprotective actions and action mechanisms of the isolated asarone as well as the alpha- and the beta-asarone obtained commercially. The isolated asarone inhibited the excitotoxicity induced by the exposure of cortical cultures for 15 min to 300 microM NMDA in a concentration-dependent manner, with the IC50 of 56.1 microg/ml. The commercially obtained alpha- and beta-asarone exhibited more potent inhibitions of the NMDA-induced excitotoxicity than the isolated asarone. Their respective IC50 values were 18.2 and 26.5 microg/ml. The excitotoxicity induced by glutamate (Glu) was also inhibited, but with much less potency than the toxicity induced by NMDA. The IC50 values for the alpha-, beta-, and the isolated asarone were 89.7, 121.7, and 279.5 microg/ml, respectively. Based on the receptor-ligand binding studies using a use-dependent NMDA receptor-channel blocker [3H]MK-801, asarone inhibited the specific bindings in a concentration-dependent fashion. These results indicate that asarone, the major essential oil component in AGR, exhibits neuroprotective action against the NMDA- or Glu-induced excitotoxicity through the blockade of NMDA receptor function. The alpha-asarone was found to exhibit more potent inhibition of [3H]MK-801 bindings, which is consistent with its more potent neuroprotective action than the beta- or the isolated asarone.
authors.affiliation: College of Medicine, Department of Pharmacology, Dongguk University, Kyongju, Kyongbuk 780-714, South Korea. jscho@mail.dongguk.ac.kr
authors.forename: Jungsook
authors.initials: J
authors.lastname: Cho
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Kim
authors.forename: Jae-Yang
authors.initials: JY
authors.lastname: Kong
authors.forename: Chae Ha
authors.initials: CH
authors.lastname: Yang
authors.forename: Chang Gook
authors.initials: CG
authors.lastname: Park
mesh_terms: D029023:Acorus / Q000737:chemistry*; D000081248:Allylbenzene Derivatives; D000818:Animals; D000840:Anisoles / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D016923:Cell Death; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004622:Embryo, Mammalian; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D018698:Glutamic Acid / Q000494:pharmacology / Q000633:toxicity; D008518:Medicine, East Asian Traditional; D016202:N-Methylaspartate / Q000494:pharmacology / Q000633:toxicity; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology; D011247:Pregnancy; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
chemical_list: D000081248:Allylbenzene Derivatives; D000840:Anisoles; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D010936:Plant Extracts; D016194:Receptors, N-Methyl-D-Aspartate; C012195:asarone; D018698:Glutamic Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate