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Protective effects of glycycoumarin and procyanidin B1, active components of traditional Japanese medicine yokukansan, on amyloid beta oligomer-induced neuronal death

作者 Kanno, Hitomi; Kawakami, Zenji; Tabuchi, Masahiro; Mizoguchi, Kazushige; Ikarashi, Yasushi; Kase, Yoshio

期刊 JOURNAL OF ETHNOPHARMACOLOGY , JAN 15 2015,:159

DOI 10.1016/j.jep.2014.10.058 PubMed 25446602

摘要 Ethnopharmacological relevance: Yokukansan, a traditional Japanese (Kampo) medicine, is composed of seven medicinal herbs, and has been traditionally used to treat neurosis, insomnia, and night crying and irritability in children. Yokukansan and its constituent herbs, Glycyrrhiza and Uncaria Hook, have recently been shown to have protective effects against amyloid beta (A beta) oligomer-induced apoptosis by suppressing the activation of caspase-3 in primary cultured neurons. The aim of the present study was to identify the effective components of Glycyrrhiza and Uncaria Hook against A beta oligomer-induced neurotoxicity. We also attempted to clarify the mechanisms by which yokukansan and these herbs, as well as their components, suppressed the activation of caspase-3 in A beta oligomer-treated neurons.Materials and methods: Rat primary cultured cortical neurons were treated with A beta oligomer (3 mu M). The protective effects of 16 components derived from Glycyrrhiza or Uncaria Hook against A beta oligomer-induced neurotoxicity were determined using the MTT reduction assay 48 h after the treatment. The suppressive effects of the test substances, i.e., yokukansan, Glycyrrhiza, Uncaria Hook, and screened components, on the A beta oligomer-induced activation of caspase-3(/7) were evaluated using the caspase-Glo assay 48 h after the A beta oligomer treatment. The suppressive effects of the test substances on the activation of caspase-8 and -9, both of which are located upstream of caspase-3, were also examined 24 h after the A beta oligomer treatment.Results: Two of the 16 components tested, glycycoumarin derived from Glycyrrhiza and procyanidin B1 derived from Uncaria Hook, significantly inhibited A beta oligomer-induced neuronal death in a dose-dependent manner. Glycyrrhiza, Uncaria Hook, and yokukansan significantly suppressed the A beta oligomer-induced activation of caspase-3 as well as caspase-8 and -9. Glycycoumarin also suppressed the activation of caspase-3, but not caspase-8 and -9. Procyanidin B1 suppressed the activation of caspase-3, -8, and -9.Conclusions: Our results demonstrated that glycycoumarin and procyanidin B1 had ameliorative effects on A beta oligomer-induced neurotoxicity. The neuroprotective effects of glycycoumarin are thought to be due to the attenuated activation of caspase-3, but not caspase-8 or -9. Procyanidin B1, as well as yokukansan, Glycyrrhiza, and Uncaria Hook, may attenuate the activation of caspase-3 by inhibiting that of caspase-8 and -9. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

涉及物种 甘草属 Glycyrrhiza