Isoliquiritigenin is a Novel NMDA Receptor Antagonist in Kampo Medicine Yokukansan |
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Authors: | Zenji Kawakami Yasushi Ikarashi Yoshio Kase |
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Institution: | (1) Tsumura Research Laboratories, Tsumura & Co, 3586 Yoshiwara, Ami-Machi, Inashiki-Gun Ibaraki, 300-1192, Japan |
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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 Ca2+ influx assays, only isoliquiritigenin bound to NMDA receptors and inhibited the glutamate-induced increase in Ca2+ influx. Glycycoumarin and 18β-glycyrrhetinic acid bound to NMDA receptors, but did not inhibit the Ca2+ 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. |
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