title: Isoliquiritigenin is a novel NMDA receptor antagonist in kampo medicine yokukansan.
abstract: Effects of a traditional Japanese medicine, yokukansan, which is composed of seven medicinal herbs, on glutamate-induced cell death were examined using primary cultured rat cortical neurons. Yokukansan (10-300 μg/ml) inhibited the 100 μM glutamate-induced neuronal death in a concentration-dependent manner. Among seven constituent herbs, higher potency of protection was found in Uncaria thorn (UT) and Glycyrrhiza root (GR). A similar neuroprotective effect was found in four components (geissoschizine methyl ether, hirsuteine, hirsutine, and rhynchophylline) in UT and four components (glycycoumarin, isoliquiritigenin, liquiritin, and 18β-glycyrrhetinic acid) in GR. In the NMDA receptor binding and receptor-linked Ca(2+) influx assays, only isoliquiritigenin bound to NMDA receptors and inhibited the glutamate-induced increase in Ca(2+) influx. Glycycoumarin and 18β-glycyrrhetinic acid bound to NMDA receptors, but did not inhibit the Ca(2+) influx. The four UT-derived components did not bind to NMDA receptors. The present results suggest that neuroprotective components (isoliquiritigenin, glycycoumarin, liquiritin, and 18β-glycyrrhetinic acid in GR and geissoschizine methyl ether, hirsuteine, hirsutine, and rhynchophylline in UT) are contained in yokukansan, and isoliquiritigenin, which is one of them, is a novel NMDA receptor antagonist.
authors.affiliation: Tsumura Research Laboratories, Tsumura & Co, 3586 Yoshiwara, Ami-Machi, Inashiki-Gun, Ibaraki 300-1192, Japan. kawakami_zenji@mail.tsumura.co.jp
authors.forename: Zenji
authors.initials: Z
authors.lastname: Kawakami
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ikarashi
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kase
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D047188:Chalcones / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018698:Glutamic Acid / Q000633:toxicity; D020835:Medicine, Kampo; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D047188:Chalcones; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; C524644:Yi-Gan San; D018698:Glutamic Acid; C040920:isoliquiritigenin; D002118:Calcium