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Yoshio Kase - One of the best experts on this subject based on the ideXlab platform.

  • by Augmenting Gene Expression of
    2016
    Co-Authors: Hitomi Kanno, Zenji Kawakami, Kazushige Mizoguchi, Yasushi Ikarashi, Yoshio Kase
    Abstract:

    Effects of the kampo medicine Yokukansan on gene expression of the cystine/ glutamate antiporter system Xc2, which protects against glutamate-induced cytotoxicity, were examined in Pheochromocytoma cells (PC12 cells). Yokukansan inhibited glutamate-induced PC12 cell death. Similar cytoprotective effects were found in Uncaria hook. Experiments to clarify the active compounds revealed that geissoschizine methyl ether, hirsuteine, hirsutine, and procyanidin B1 in Uncaria hook, had cytoprotective effects. These components enhanced gene expressions of system Xc2 subunits xCT and 4F2hc, and also ameliorated the glutamate-induced decrease in glutathione levels. These results suggest that the cytoprotective effect of Yokukansan may be attributed to geissoschizine methyl ether, hirsuteine, hirsutine, and procyanidin B1 in Uncaria hook

  • Research Article Yokukansan Increases 5-HT1A Receptors in the Prefrontal Cortex and Enhances 5-HT1A Receptor Agonist-Induced Behavioral Responses in Socially Isolated Mice
    2016
    Co-Authors: Toshiyuki Ueki, Kazushige Mizoguchi, Takuji Yamaguchi, Yasushi Ikarashi, Akinori Nishi, Tomohisa Hattori, Yoshio Kase
    Abstract:

    Copyright © 2015 Toshiyuki Ueki et al.This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The traditional Japanese medicine Yokukansan has an anxiolytic effect, which occurs after repeated administration. In this study, to investigate the underlying mechanisms, we examined the effects of repeated Yokukansan administration on serotonin 1A (5-HT 1A) receptor density and affinity and its expression at both mRNA and protein levels in the prefrontal cortex (PFC) of socially isolated mice. Moreover, we examined the effects of Yokukansan on a 5-HT 1A receptor-mediated behavioral response. Male mice were subjected to social isolation stress for 6 weeks and simultaneously treated with Yokukansan. Thereafter, the density and affinity of 5-HT 1A receptors were analyzed by a receptor-binding assay. Levels of 5-HT1A receptor protein and mRNA were also measured. Furthermore, (±)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT; a 5-HT 1A receptor agonist) was injected intraperitoneally, and rearing behavior was examined. Social isolation stress alone did not affect 5-HT 1A receptor density or affinity. However, Yokukansan significantly increased receptor density and decreased affinity concomitant with unchanged protein and mRNA levels. Yokukansan also enhanced the 8-OH-DPAT-induced decrease in rearing behavior. These results suggest that Yokukansan increases 5-HT 1A receptors in the PFC of socially isolated mice and enhances their function, which might underlie its anxiolytic effects. 1

  • Yokukansan Increases 5-HT1A Receptors in the Prefrontal Cortex and Enhances 5-HT1A Receptor Agonist-Induced Behavioral Responses in Socially Isolated Mice
    Evidence-based complementary and alternative medicine : eCAM, 2015
    Co-Authors: Toshiyuki Ueki, Kazushige Mizoguchi, Takuji Yamaguchi, Yasushi Ikarashi, Akinori Nishi, Tomohisa Hattori, Yoshio Kase
    Abstract:

    The traditional Japanese medicine Yokukansan has an anxiolytic effect, which occurs after repeated administration. In this study, to investigate the underlying mechanisms, we examined the effects of repeated Yokukansan administration on serotonin 1A (5-HT1A) receptor density and affinity and its expression at both mRNA and protein levels in the prefrontal cortex (PFC) of socially isolated mice. Moreover, we examined the effects of Yokukansan on a 5-HT1A receptor-mediated behavioral response. Male mice were subjected to social isolation stress for 6 weeks and simultaneously treated with Yokukansan. Thereafter, the density and affinity of 5-HT1A receptors were analyzed by a receptor-binding assay. Levels of 5-HT1A receptor protein and mRNA were also measured. Furthermore, (±)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT; a 5-HT1A receptor agonist) was injected intraperitoneally, and rearing behavior was examined. Social isolation stress alone did not affect 5-HT1A receptor density or affinity. However, Yokukansan significantly increased receptor density and decreased affinity concomitant with unchanged protein and mRNA levels. Yokukansan also enhanced the 8-OH-DPAT-induced decrease in rearing behavior. These results suggest that Yokukansan increases 5-HT1A receptors in the PFC of socially isolated mice and enhances their function, which might underlie its anxiolytic effects.

  • Yokukansan a traditional japanese medicine decreases head twitch behaviors and serotonin 2a receptors in the prefrontal cortex of isolation stressed mice
    Journal of Ethnopharmacology, 2015
    Co-Authors: Toshiyuki Ueki, Kazushige Mizoguchi, Takuji Yamaguchi, Kyoji Sekiguchi, Yasushi Ikarashi, Akinori Nishi, Yoshio Kase
    Abstract:

    Abstract Ethnopharmacological relevance Yokukansan, a traditional Japanese (Kampo) medicine, has recently been used to treat the behavioral and psychological symptoms of dementia (BPSD), including aggressiveness, excitability, and hallucination. The present study was designed to investigate the mechanisms underlying the ameliorative effects of Yokukansan on BPSD using animals exhibiting hallucination-like behaviors. For this purpose, we initially examined whether chronic isolation stress increases the frequency of hallucination in response to a psychedelic drug. Using this animal model, we next examined the effects of Yokukansan on drug-induced hallucination-like behaviors. Finally, we examined the density and mRNA levels of serotonin 2A (5-HT 2A ) receptors. Materials and methods Male mice were subjected to isolation stress for six weeks. Yokukansan was incorporated into food pellets, and administered to the mice for six weeks. In some experiments, Yokukansan and each of seven constituent herbs were administered orally to the mice for the last two weeks during the six-week period of isolation stress. A 5-HT 2A receptor agonist, 2,5-dimethoxy-4-iodoamphetamine (DOI, 2.5 mg/kg), was injected into the mice, and head-twitch behaviors were quantified. The binding sites of 5-HT 2A receptors on the plasma membrane of the prefrontal cortex (PFC) were assessed by a receptor-binding assay using tritium-labeled ketanserin, and the density and affinity were calculated from a Scatchard plot. The level of mRNAs was measured by PCR analyses. Results Isolation stress enhanced the frequency of the DOI-induced head-twitch response, and Yokukansan treatment by feeding significantly reduced this enhancement. Isolation stress significantly increased the 5-HT 2A receptor density in the PFC, and Yokukansan treatment by feeding as well as administration significantly down-regulated this increase. Isolation stress and Yokukansan did not affect the affinity. Among seven constituent herbs, Bupleurum Root, Uncaria Hook, Japanese Angelica Root, and Glycyrrhiza down-regulated the increase, but statistically not significant, in which their efficacies were over 50% relative to Yokukansan. Neither isolation stress nor Yokukansan affected mRNA levels of 5-HT 2A receptors. Conclusion Yokukansan attenuated drug-induced hallucination-like behaviors in isolated mice, which is suggested to be mediated by 5-HT 2A receptor down-regulation in the PFC. This mechanism may underlie the ameliorative effects of Yokukansan on hallucination.

  • Yokukansan, a kampo medicine, protects PC12 cells from glutamate-induced death by augmenting gene expression of cystine/glutamate antiporter system Xc-.
    PloS one, 2014
    Co-Authors: Hitomi Kanno, Zenji Kawakami, Kazushige Mizoguchi, Yasushi Ikarashi, Yoshio Kase
    Abstract:

    Effects of the kampo medicine Yokukansan on gene expression of the cystine/glutamate antiporter system Xc−, which protects against glutamate-induced cytotoxicity, were examined in Pheochromocytoma cells (PC12 cells). Yokukansan inhibited glutamate-induced PC12 cell death. Similar cytoprotective effects were found in Uncaria hook. Experiments to clarify the active compounds revealed that geissoschizine methyl ether, hirsuteine, hirsutine, and procyanidin B1 in Uncaria hook, had cytoprotective effects. These components enhanced gene expressions of system Xc− subunits xCT and 4F2hc, and also ameliorated the glutamate-induced decrease in glutathione levels. These results suggest that the cytoprotective effect of Yokukansan may be attributed to geissoschizine methyl ether, hirsuteine, hirsutine, and procyanidin B1 in Uncaria hook.

Yasushi Ikarashi - One of the best experts on this subject based on the ideXlab platform.

  • by Augmenting Gene Expression of
    2016
    Co-Authors: Hitomi Kanno, Zenji Kawakami, Kazushige Mizoguchi, Yasushi Ikarashi, Yoshio Kase
    Abstract:

    Effects of the kampo medicine Yokukansan on gene expression of the cystine/ glutamate antiporter system Xc2, which protects against glutamate-induced cytotoxicity, were examined in Pheochromocytoma cells (PC12 cells). Yokukansan inhibited glutamate-induced PC12 cell death. Similar cytoprotective effects were found in Uncaria hook. Experiments to clarify the active compounds revealed that geissoschizine methyl ether, hirsuteine, hirsutine, and procyanidin B1 in Uncaria hook, had cytoprotective effects. These components enhanced gene expressions of system Xc2 subunits xCT and 4F2hc, and also ameliorated the glutamate-induced decrease in glutathione levels. These results suggest that the cytoprotective effect of Yokukansan may be attributed to geissoschizine methyl ether, hirsuteine, hirsutine, and procyanidin B1 in Uncaria hook

  • Research Article Yokukansan Increases 5-HT1A Receptors in the Prefrontal Cortex and Enhances 5-HT1A Receptor Agonist-Induced Behavioral Responses in Socially Isolated Mice
    2016
    Co-Authors: Toshiyuki Ueki, Kazushige Mizoguchi, Takuji Yamaguchi, Yasushi Ikarashi, Akinori Nishi, Tomohisa Hattori, Yoshio Kase
    Abstract:

    Copyright © 2015 Toshiyuki Ueki et al.This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The traditional Japanese medicine Yokukansan has an anxiolytic effect, which occurs after repeated administration. In this study, to investigate the underlying mechanisms, we examined the effects of repeated Yokukansan administration on serotonin 1A (5-HT 1A) receptor density and affinity and its expression at both mRNA and protein levels in the prefrontal cortex (PFC) of socially isolated mice. Moreover, we examined the effects of Yokukansan on a 5-HT 1A receptor-mediated behavioral response. Male mice were subjected to social isolation stress for 6 weeks and simultaneously treated with Yokukansan. Thereafter, the density and affinity of 5-HT 1A receptors were analyzed by a receptor-binding assay. Levels of 5-HT1A receptor protein and mRNA were also measured. Furthermore, (±)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT; a 5-HT 1A receptor agonist) was injected intraperitoneally, and rearing behavior was examined. Social isolation stress alone did not affect 5-HT 1A receptor density or affinity. However, Yokukansan significantly increased receptor density and decreased affinity concomitant with unchanged protein and mRNA levels. Yokukansan also enhanced the 8-OH-DPAT-induced decrease in rearing behavior. These results suggest that Yokukansan increases 5-HT 1A receptors in the PFC of socially isolated mice and enhances their function, which might underlie its anxiolytic effects. 1

  • Yokukansan Increases 5-HT1A Receptors in the Prefrontal Cortex and Enhances 5-HT1A Receptor Agonist-Induced Behavioral Responses in Socially Isolated Mice
    Evidence-based complementary and alternative medicine : eCAM, 2015
    Co-Authors: Toshiyuki Ueki, Kazushige Mizoguchi, Takuji Yamaguchi, Yasushi Ikarashi, Akinori Nishi, Tomohisa Hattori, Yoshio Kase
    Abstract:

    The traditional Japanese medicine Yokukansan has an anxiolytic effect, which occurs after repeated administration. In this study, to investigate the underlying mechanisms, we examined the effects of repeated Yokukansan administration on serotonin 1A (5-HT1A) receptor density and affinity and its expression at both mRNA and protein levels in the prefrontal cortex (PFC) of socially isolated mice. Moreover, we examined the effects of Yokukansan on a 5-HT1A receptor-mediated behavioral response. Male mice were subjected to social isolation stress for 6 weeks and simultaneously treated with Yokukansan. Thereafter, the density and affinity of 5-HT1A receptors were analyzed by a receptor-binding assay. Levels of 5-HT1A receptor protein and mRNA were also measured. Furthermore, (±)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT; a 5-HT1A receptor agonist) was injected intraperitoneally, and rearing behavior was examined. Social isolation stress alone did not affect 5-HT1A receptor density or affinity. However, Yokukansan significantly increased receptor density and decreased affinity concomitant with unchanged protein and mRNA levels. Yokukansan also enhanced the 8-OH-DPAT-induced decrease in rearing behavior. These results suggest that Yokukansan increases 5-HT1A receptors in the PFC of socially isolated mice and enhances their function, which might underlie its anxiolytic effects.

  • Yokukansan a traditional japanese medicine decreases head twitch behaviors and serotonin 2a receptors in the prefrontal cortex of isolation stressed mice
    Journal of Ethnopharmacology, 2015
    Co-Authors: Toshiyuki Ueki, Kazushige Mizoguchi, Takuji Yamaguchi, Kyoji Sekiguchi, Yasushi Ikarashi, Akinori Nishi, Yoshio Kase
    Abstract:

    Abstract Ethnopharmacological relevance Yokukansan, a traditional Japanese (Kampo) medicine, has recently been used to treat the behavioral and psychological symptoms of dementia (BPSD), including aggressiveness, excitability, and hallucination. The present study was designed to investigate the mechanisms underlying the ameliorative effects of Yokukansan on BPSD using animals exhibiting hallucination-like behaviors. For this purpose, we initially examined whether chronic isolation stress increases the frequency of hallucination in response to a psychedelic drug. Using this animal model, we next examined the effects of Yokukansan on drug-induced hallucination-like behaviors. Finally, we examined the density and mRNA levels of serotonin 2A (5-HT 2A ) receptors. Materials and methods Male mice were subjected to isolation stress for six weeks. Yokukansan was incorporated into food pellets, and administered to the mice for six weeks. In some experiments, Yokukansan and each of seven constituent herbs were administered orally to the mice for the last two weeks during the six-week period of isolation stress. A 5-HT 2A receptor agonist, 2,5-dimethoxy-4-iodoamphetamine (DOI, 2.5 mg/kg), was injected into the mice, and head-twitch behaviors were quantified. The binding sites of 5-HT 2A receptors on the plasma membrane of the prefrontal cortex (PFC) were assessed by a receptor-binding assay using tritium-labeled ketanserin, and the density and affinity were calculated from a Scatchard plot. The level of mRNAs was measured by PCR analyses. Results Isolation stress enhanced the frequency of the DOI-induced head-twitch response, and Yokukansan treatment by feeding significantly reduced this enhancement. Isolation stress significantly increased the 5-HT 2A receptor density in the PFC, and Yokukansan treatment by feeding as well as administration significantly down-regulated this increase. Isolation stress and Yokukansan did not affect the affinity. Among seven constituent herbs, Bupleurum Root, Uncaria Hook, Japanese Angelica Root, and Glycyrrhiza down-regulated the increase, but statistically not significant, in which their efficacies were over 50% relative to Yokukansan. Neither isolation stress nor Yokukansan affected mRNA levels of 5-HT 2A receptors. Conclusion Yokukansan attenuated drug-induced hallucination-like behaviors in isolated mice, which is suggested to be mediated by 5-HT 2A receptor down-regulation in the PFC. This mechanism may underlie the ameliorative effects of Yokukansan on hallucination.

  • Yokukansan a kampo medicine protects pc12 cells from glutamate induced death by augmenting gene expression of cystine glutamate antiporter system xc
    PLOS ONE, 2014
    Co-Authors: Hitomi Kanno, Zenji Kawakami, Kazushige Mizoguchi, Yasushi Ikarashi, Yoshio Kase
    Abstract:

    Effects of the kampo medicine Yokukansan on gene expression of the cystine/glutamate antiporter system Xc−, which protects against glutamate-induced cytotoxicity, were examined in Pheochromocytoma cells (PC12 cells). Yokukansan inhibited glutamate-induced PC12 cell death. Similar cytoprotective effects were found in Uncaria hook. Experiments to clarify the active compounds revealed that geissoschizine methyl ether, hirsuteine, hirsutine, and procyanidin B1 in Uncaria hook, had cytoprotective effects. These components enhanced gene expressions of system Xc− subunits xCT and 4F2hc, and also ameliorated the glutamate-induced decrease in glutathione levels. These results suggest that the cytoprotective effect of Yokukansan may be attributed to geissoschizine methyl ether, hirsuteine, hirsutine, and procyanidin B1 in Uncaria hook.

Zenji Kawakami - One of the best experts on this subject based on the ideXlab platform.

  • by Augmenting Gene Expression of
    2016
    Co-Authors: Hitomi Kanno, Zenji Kawakami, Kazushige Mizoguchi, Yasushi Ikarashi, Yoshio Kase
    Abstract:

    Effects of the kampo medicine Yokukansan on gene expression of the cystine/ glutamate antiporter system Xc2, which protects against glutamate-induced cytotoxicity, were examined in Pheochromocytoma cells (PC12 cells). Yokukansan inhibited glutamate-induced PC12 cell death. Similar cytoprotective effects were found in Uncaria hook. Experiments to clarify the active compounds revealed that geissoschizine methyl ether, hirsuteine, hirsutine, and procyanidin B1 in Uncaria hook, had cytoprotective effects. These components enhanced gene expressions of system Xc2 subunits xCT and 4F2hc, and also ameliorated the glutamate-induced decrease in glutathione levels. These results suggest that the cytoprotective effect of Yokukansan may be attributed to geissoschizine methyl ether, hirsuteine, hirsutine, and procyanidin B1 in Uncaria hook

  • Yokukansan, a kampo medicine, protects PC12 cells from glutamate-induced death by augmenting gene expression of cystine/glutamate antiporter system Xc-.
    PloS one, 2014
    Co-Authors: Hitomi Kanno, Zenji Kawakami, Kazushige Mizoguchi, Yasushi Ikarashi, Yoshio Kase
    Abstract:

    Effects of the kampo medicine Yokukansan on gene expression of the cystine/glutamate antiporter system Xc−, which protects against glutamate-induced cytotoxicity, were examined in Pheochromocytoma cells (PC12 cells). Yokukansan inhibited glutamate-induced PC12 cell death. Similar cytoprotective effects were found in Uncaria hook. Experiments to clarify the active compounds revealed that geissoschizine methyl ether, hirsuteine, hirsutine, and procyanidin B1 in Uncaria hook, had cytoprotective effects. These components enhanced gene expressions of system Xc− subunits xCT and 4F2hc, and also ameliorated the glutamate-induced decrease in glutathione levels. These results suggest that the cytoprotective effect of Yokukansan may be attributed to geissoschizine methyl ether, hirsuteine, hirsutine, and procyanidin B1 in Uncaria hook.

  • Yokukansan a kampo medicine protects pc12 cells from glutamate induced death by augmenting gene expression of cystine glutamate antiporter system xc
    PLOS ONE, 2014
    Co-Authors: Hitomi Kanno, Zenji Kawakami, Kazushige Mizoguchi, Yasushi Ikarashi, Yoshio Kase
    Abstract:

    Effects of the kampo medicine Yokukansan on gene expression of the cystine/glutamate antiporter system Xc−, which protects against glutamate-induced cytotoxicity, were examined in Pheochromocytoma cells (PC12 cells). Yokukansan inhibited glutamate-induced PC12 cell death. Similar cytoprotective effects were found in Uncaria hook. Experiments to clarify the active compounds revealed that geissoschizine methyl ether, hirsuteine, hirsutine, and procyanidin B1 in Uncaria hook, had cytoprotective effects. These components enhanced gene expressions of system Xc− subunits xCT and 4F2hc, and also ameliorated the glutamate-induced decrease in glutathione levels. These results suggest that the cytoprotective effect of Yokukansan may be attributed to geissoschizine methyl ether, hirsuteine, hirsutine, and procyanidin B1 in Uncaria hook.

  • Protective effects of glycycoumarin and procyanidin B1, active components of traditional Japanese medicine Yokukansan, on amyloid β oligomer-induced neuronal death.
    Journal of ethnopharmacology, 2014
    Co-Authors: Hitomi Kanno, Zenji Kawakami, Kazushige Mizoguchi, Yasushi Ikarashi, Masahiro Tabuchi, Yoshio Kase
    Abstract:

    Abstract 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 β (Aβ) 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 Aβ 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 Aβ oligomer-treated neurons. Materials and methods Rat primary cultured cortical neurons were treated with Aβ oligomer (3 μM). The protective effects of 16 components derived from Glycyrrhiza or Uncaria Hook against Aβ 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 Aβ oligomer-induced activation of caspase-3(/7) were evaluated using the caspase-Glo assay 48 h after the Aβ 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 Aβ oligomer treatment. Results Two of the 16 components tested, glycycoumarin derived from Glycyrrhiza and procyanidin B1 derived from Uncaria Hook, significantly inhibited Aβ oligomer-induced neuronal death in a dose-dependent manner. Glycyrrhiza, Uncaria Hook, and Yokukansan significantly suppressed the Aβ 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 Aβ 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.

  • Effects of Yokukansan on gene expressions of system Xc− subunits xCT (A) and 4F2hc (B) in PC12 cells.
    2014
    Co-Authors: Hitomi Kanno, Zenji Kawakami, Kazushige Mizoguchi, Yasushi Ikarashi, Yoshio Kase
    Abstract:

    The effects of Yokukansan (YKS: 62.5, 125, and 250 µg/mL) was examined 6 h after incubation under the conditions with or without 2.5 mM glutamate (Glu). Control (Ctrl) did not contain glutamate. The gene expression level in each sample was determined as the mean value of triplicate determinations. Each data calculated as the ratio of endogenous control gene GAPDH represents as the mean ± S.E.M. (n = 3). *P

Hitomi Kanno - One of the best experts on this subject based on the ideXlab platform.

  • by Augmenting Gene Expression of
    2016
    Co-Authors: Hitomi Kanno, Zenji Kawakami, Kazushige Mizoguchi, Yasushi Ikarashi, Yoshio Kase
    Abstract:

    Effects of the kampo medicine Yokukansan on gene expression of the cystine/ glutamate antiporter system Xc2, which protects against glutamate-induced cytotoxicity, were examined in Pheochromocytoma cells (PC12 cells). Yokukansan inhibited glutamate-induced PC12 cell death. Similar cytoprotective effects were found in Uncaria hook. Experiments to clarify the active compounds revealed that geissoschizine methyl ether, hirsuteine, hirsutine, and procyanidin B1 in Uncaria hook, had cytoprotective effects. These components enhanced gene expressions of system Xc2 subunits xCT and 4F2hc, and also ameliorated the glutamate-induced decrease in glutathione levels. These results suggest that the cytoprotective effect of Yokukansan may be attributed to geissoschizine methyl ether, hirsuteine, hirsutine, and procyanidin B1 in Uncaria hook

  • Yokukansan, a kampo medicine, protects PC12 cells from glutamate-induced death by augmenting gene expression of cystine/glutamate antiporter system Xc-.
    PloS one, 2014
    Co-Authors: Hitomi Kanno, Zenji Kawakami, Kazushige Mizoguchi, Yasushi Ikarashi, Yoshio Kase
    Abstract:

    Effects of the kampo medicine Yokukansan on gene expression of the cystine/glutamate antiporter system Xc−, which protects against glutamate-induced cytotoxicity, were examined in Pheochromocytoma cells (PC12 cells). Yokukansan inhibited glutamate-induced PC12 cell death. Similar cytoprotective effects were found in Uncaria hook. Experiments to clarify the active compounds revealed that geissoschizine methyl ether, hirsuteine, hirsutine, and procyanidin B1 in Uncaria hook, had cytoprotective effects. These components enhanced gene expressions of system Xc− subunits xCT and 4F2hc, and also ameliorated the glutamate-induced decrease in glutathione levels. These results suggest that the cytoprotective effect of Yokukansan may be attributed to geissoschizine methyl ether, hirsuteine, hirsutine, and procyanidin B1 in Uncaria hook.

  • Yokukansan a kampo medicine protects pc12 cells from glutamate induced death by augmenting gene expression of cystine glutamate antiporter system xc
    PLOS ONE, 2014
    Co-Authors: Hitomi Kanno, Zenji Kawakami, Kazushige Mizoguchi, Yasushi Ikarashi, Yoshio Kase
    Abstract:

    Effects of the kampo medicine Yokukansan on gene expression of the cystine/glutamate antiporter system Xc−, which protects against glutamate-induced cytotoxicity, were examined in Pheochromocytoma cells (PC12 cells). Yokukansan inhibited glutamate-induced PC12 cell death. Similar cytoprotective effects were found in Uncaria hook. Experiments to clarify the active compounds revealed that geissoschizine methyl ether, hirsuteine, hirsutine, and procyanidin B1 in Uncaria hook, had cytoprotective effects. These components enhanced gene expressions of system Xc− subunits xCT and 4F2hc, and also ameliorated the glutamate-induced decrease in glutathione levels. These results suggest that the cytoprotective effect of Yokukansan may be attributed to geissoschizine methyl ether, hirsuteine, hirsutine, and procyanidin B1 in Uncaria hook.

  • Protective effects of glycycoumarin and procyanidin B1, active components of traditional Japanese medicine Yokukansan, on amyloid β oligomer-induced neuronal death.
    Journal of ethnopharmacology, 2014
    Co-Authors: Hitomi Kanno, Zenji Kawakami, Kazushige Mizoguchi, Yasushi Ikarashi, Masahiro Tabuchi, Yoshio Kase
    Abstract:

    Abstract 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 β (Aβ) 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 Aβ 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 Aβ oligomer-treated neurons. Materials and methods Rat primary cultured cortical neurons were treated with Aβ oligomer (3 μM). The protective effects of 16 components derived from Glycyrrhiza or Uncaria Hook against Aβ 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 Aβ oligomer-induced activation of caspase-3(/7) were evaluated using the caspase-Glo assay 48 h after the Aβ 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 Aβ oligomer treatment. Results Two of the 16 components tested, glycycoumarin derived from Glycyrrhiza and procyanidin B1 derived from Uncaria Hook, significantly inhibited Aβ oligomer-induced neuronal death in a dose-dependent manner. Glycyrrhiza, Uncaria Hook, and Yokukansan significantly suppressed the Aβ 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 Aβ 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.

  • Ameliorative effect of Yokukansan on glutamate-induced decrease in GSH levels in PC12 cells.
    2014
    Co-Authors: Hitomi Kanno, Zenji Kawakami, Kazushige Mizoguchi, Yasushi Ikarashi, Yoshio Kase
    Abstract:

    The GSH levels in 2.5 mM glutamate (Glu) and Glu+Yokukansan (YKS: 62.5, 125, and 250 µg/mL)-treated groups were measured 24 h after the addition of Glu to the medium. Control (Ctrl) did not contain glutamate. Each data calculated as a percentage of the control represents the mean ± S.E.M. (n = 6). ***P

Masahiro Tabuchi - One of the best experts on this subject based on the ideXlab platform.

  • Protective effects of glycycoumarin and procyanidin B1, active components of traditional Japanese medicine Yokukansan, on amyloid β oligomer-induced neuronal death.
    Journal of ethnopharmacology, 2014
    Co-Authors: Hitomi Kanno, Zenji Kawakami, Kazushige Mizoguchi, Yasushi Ikarashi, Masahiro Tabuchi, Yoshio Kase
    Abstract:

    Abstract 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 β (Aβ) 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 Aβ 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 Aβ oligomer-treated neurons. Materials and methods Rat primary cultured cortical neurons were treated with Aβ oligomer (3 μM). The protective effects of 16 components derived from Glycyrrhiza or Uncaria Hook against Aβ 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 Aβ oligomer-induced activation of caspase-3(/7) were evaluated using the caspase-Glo assay 48 h after the Aβ 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 Aβ oligomer treatment. Results Two of the 16 components tested, glycycoumarin derived from Glycyrrhiza and procyanidin B1 derived from Uncaria Hook, significantly inhibited Aβ oligomer-induced neuronal death in a dose-dependent manner. Glycyrrhiza, Uncaria Hook, and Yokukansan significantly suppressed the Aβ 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 Aβ 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.

  • simultaneous quantitative analyses of indole and oxindole alkaloids of uncaria hook in rat plasma and brain after oral administration of the traditional japanese medicine Yokukansan using high performance liquid chromatography with tandem mass spectr
    Biomedical Chromatography, 2013
    Co-Authors: Hirotaka Kushida, Yasushi Ikarashi, Masahiro Tabuchi, Miwako Fukutake, Takao Katsuhara, Hiroaki Nishimura, Masanao Kanitani, Yoshio Kase
    Abstract:

    Uncaria Hook (UH) alkaloids are involved in the beneficial effects of Yokukansan. However, the pharmacokinetics of UH alkaloids after oral administration of Yokukansan has not yet been sufficiently investigated. Therefore, we developed and validated a sensitive and specific high-performance liquid chromatography with tandem mass spectrometry (LC/MS/MS) method for the simultaneous quantitation of seven UH alkaloids (corynoxeine, isocorynoxeine, rhynchophylline, isorhynchophylline, hirsutine, hirsuteine and geissoschizine methyl ether) in rat plasma and brain. After protein precipitation with acetonitrile, chromatographic separation was performed using an Ascentis Express RP-amide column, with gradient elution with 0.2% formic acid and acetonitrile at 0.3 mL/min. All analytes in the plasma and brain showed good linearity over a wide concentration range (r > 0.995). Intra-day and inter-day variations of each constituent were 8.6 and 8.0% or less in the plasma, and 14.9 and 15.0% or less in the brain, respectively. The validated LC/MS/MS method was applied in the pharmacokinetic studies of UH alkaloids after oral administration of Yokukansan to rats. In the plasma, rhynchophylline, hirsutine, hirsuteine and geissoschizine methyl ether were detected, but only geissoschizine methyl ether was detected in the brain. These results suggest that geissoschizine methyl ether is an important constituent of the pharmacological effects of Yokukansan.

  • Glycyrrhiza and Uncaria Hook contribute to protective effect of traditional Japanese medicine Yokukansan against amyloid β oligomer-induced neuronal death.
    Journal of ethnopharmacology, 2013
    Co-Authors: Hitomi Kanno, Zenji Kawakami, Kazushige Mizoguchi, Yasushi Ikarashi, Masahiro Tabuchi, Seiichi Iizuka, Yoshio Kase
    Abstract:

    Abstract Ethnopharmacological relevance Yokukansan, a traditional Japanese (Kampo) medicine, composed of seven medicinal herbs has been traditionally used to treat neurosis, insomnia, and night crying and irritability in children. Recently, this medicine has been reported to improve the behavioral and psychological symptoms of dementia (BPSD) that often become problematic in patients with Alzheimer's disease (AD). Aim of the study Amyloid β (Aβ) oligomers, which are extremely toxic to neurons, are involved in neurodegeneration in AD. In animals, Yokukansan has been proven to improve memory impairments and BPSD-like behavior in transgenic mice overexpressing amyloid precursor protein and mice intracerebroventricularly injected with Aβ oligomers. These results suggest that Yokukansan is potentially able to reduce the neurotoxicity of Aβ oligomers. Therefore, the present study aimed to explore the improving effects brought by Yokukansan that consists of seven herbs for Aβ oligomer-induced neurotoxicity in vitro and to identify the candidate herbs in Yokukansan's action. Materials and methods Primary cultured rat cortical neurons were used. Neurotoxicity induced by Aβ oligomers (3 µM) and improving effects of Yokukansan (300–1000 µg/mL) and its constituent herbs were evaluated in MTT assay, DNA fragmentation analysis, and electron microscopic analysis at 48 h after treatment with Aβ oligomers and drugs. Moreover, changes in expression of genes related to endoplasmic reticulum (ER) stress and in caspase-3 activity that is the enzyme closely related to apoptosis were analyzed to investigate the underlying mechanisms. Results Yokukansan ameliorated Aβ oligomer-induced neuronal damage in a dose-dependent manner in the MTT assay. This drug also suppressed DNA fragmentation caused by Aβ oligomers. Electron microscopic analysis suggested that Yokukansan reduced karyopyknosis and the expansion of rough ER caused by Aβ oligomers. However, neither Aβ oligomers nor Yokukansan affected the mRNA expression of any ER stress-related genes, including CHOP and GRP78. On the other hand, Yokukansan dose-dependently suppressed Aβ oligomer-induced activation of caspase-3. Among the seven constituents of Yokukansan, Glycyrrhiza and Uncaria Hook (60–200 µg/mL) suppressed Aβ oligomer-induced neuronal damage, DNA fragmentation, karyopyknosis, and caspase-3 activation to almost the same extent as Yokukansan. Conclusions The present results suggest that Yokukansan possesses an ameliorative effect against Aβ oligomer-induced neuronal apoptosis through the suppression of caspase-3 activation. Glycyrrhiza and Uncaria Hook may, at least in part, contribute to the neuroprotective effect of Yokukansan. These mechanisms may underlie the improving effects of Yokukansan on memory impairment and BPSD-like behaviors induced by Aβ oligomers.

  • Simultaneous quantitative analyses of indole and oxindole alkaloids of Uncaria Hook in rat plasma and brain after oral administration of the traditional Japanese medicine Yokukansan using high-performance liquid chromatography with tandem mass spectr
    Biomedical chromatography : BMC, 2013
    Co-Authors: Hirotaka Kushida, Yasushi Ikarashi, Masahiro Tabuchi, Miwako Fukutake, Takao Katsuhara, Hiroaki Nishimura, Masanao Kanitani, Yoshio Kase
    Abstract:

    Uncaria Hook (UH) alkaloids are involved in the beneficial effects of Yokukansan. However, the pharmacokinetics of UH alkaloids after oral administration of Yokukansan has not yet been sufficiently investigated. Therefore, we developed and validated a sensitive and specific high-performance liquid chromatography with tandem mass spectrometry (LC/MS/MS) method for the simultaneous quantitation of seven UH alkaloids (corynoxeine, isocorynoxeine, rhynchophylline, isorhynchophylline, hirsutine, hirsuteine and geissoschizine methyl ether) in rat plasma and brain. After protein precipitation with acetonitrile, chromatographic separation was performed using an Ascentis Express RP-amide column, with gradient elution with 0.2% formic acid and acetonitrile at 0.3 mL/min. All analytes in the plasma and brain showed good linearity over a wide concentration range (r > 0.995). Intra-day and inter-day variations of each constituent were 8.6 and 8.0% or less in the plasma, and 14.9 and 15.0% or less in the brain, respectively. The validated LC/MS/MS method was applied in the pharmacokinetic studies of UH alkaloids after oral administration of Yokukansan to rats. In the plasma, rhynchophylline, hirsutine, hirsuteine and geissoschizine methyl ether were detected, but only geissoschizine methyl ether was detected in the brain. These results suggest that geissoschizine methyl ether is an important constituent of the pharmacological effects of Yokukansan. Copyright © 2013 John Wiley & Sons, Ltd.

  • The Blood–Brain Barrier Permeability of 18β-Glycyrrhetinic Acid, a Major Metabolite of Glycyrrhizin in Glycyrrhiza Root, a Constituent of the Traditional Japanese Medicine Yokukansan
    Cellular and Molecular Neurobiology, 2012
    Co-Authors: Masahiro Tabuchi, Zenji Kawakami, Yasushi Ikarashi, Sachiko Imamura, Yoshio Kase
    Abstract:

    18β-Glycyrrhetinic acid (GA) is a major metabolite of glycyrrhizin (GL), which is one of the components of glycyrrhiza root, a constituent herb of the traditional Japanese medicine Yokukansan . It is well known that most GL is metabolized to GA in the intestine by bacteria. A previous in vitro study using cultured rat cortical astrocytes suggested that GA activates glutamate transport, which is a putative mechanism of the psychotropic effect of Yokukansan . To activate the glutamate transport in the brain, GA must be absorbed into the blood after oral administration of Yokukansan and then cross the blood–brain barrier (BBB) to reach the brain. However, there is no data on the BBB permeability of GA derived from Yokukansan . In the present study, the BBB permeability of GA was investigated in both in vivo and in vitro studies. In the in vivo study, GA was detected in the plasma, brain, and cerebrospinal fluid of rats orally administered Yokukansan . In the in vitro study using a BBB model composed of co-culture of endothelial cells, pericytes, and astrocytes, the permeability rate and apparent permeability coefficient of GA were found to be 13.3 ± 0.5 % and 16.5 ± 0.7 × 10^−6 cm/s. These in vivo and in vitro results suggest that GL in orally administered Yokukansan is absorbed into the blood as GA, and then reaches the brain through the BBB. This evidence further supports the possibility that GA is an active component in the psychotropic effect of Yokukansan .