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Isoliquiritigenin is a Novel NMDA Receptor Antagonist in Kampo Medicine Yokukansan

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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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  1. Tsumura Research Laboratories, Tsumura & Co, 3586 Yoshiwara, Ami-Machi, Inashiki-Gun, Ibaraki, 300-1192, Japan

    Zenji Kawakami, Yasushi Ikarashi & Yoshio Kase

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  1. Zenji Kawakami
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  2. Yasushi Ikarashi
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  3. Yoshio Kase
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Correspondence to Zenji Kawakami.

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Kawakami, Z., Ikarashi, Y. & Kase, Y. Isoliquiritigenin is a Novel NMDA Receptor Antagonist in Kampo Medicine Yokukansan. Cell Mol Neurobiol 31, 1203–1212 (2011). https://doi.org/10.1007/s10571-011-9722-1

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  • DOI: https://doi.org/10.1007/s10571-011-9722-1

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