Neuroprotective effects of yokukansan, a traditional japanese medicine, on glutamate-mediated excitotoxicity in cultured cells

Kawakami, Zenji; Kanno, Hitomi; Ueki, Toshiyuki; Terawaki, Kiyoshi; Tabuchi, Masahiro; Ikarashi, Yasushi; Kase, Yoshio

doi:10.1016/j.neuroscience.2009.02.004

Cited by 97 publications

(82 citation statements)

References 48 publications

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“…In order to clarify the hypothesis, more recently, we demonstrated in cultured astrocytes that not only the uptake of glutamate into astrocytes but also the levels of proteins and mRNA expressions of GLAST significantly decreased under TD condition, and these decreases were ameliorated by treatment with TJ-54. 48) In addition, TJ-54 inhibited glutamate-induced PC12 cell death. 48) These results suggest that TJ-54 may exert a neuroprotective effect against the glutamate excitatory neurotoxicity not only by amelioration of dysfunction of astrocytes but also by direct protection of neuronal cells.…”

Section: Discussionmentioning

confidence: 97%

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Effects of Yokukansan, a Traditional Japanese Medicine, on Memory Disturbance and Behavioral and Psychological Symptoms of Dementia in Thiamine-Deficient Rats

Ikarashi

Iizuka

Imamura

et al. 2009

Biological & Pharmaceutical Bulletin

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Behavioral and psychological symptoms of dementia (BPSD), including anxiety, depression, excitement, anger, hallucination, and roaming, are seen in patients with Alzheimer's disease and other forms of senile dementia. 1,2) To date, although atypical or conventional antipsychotic medications are used to treat BPSD, drug-induced extrapyramidal symptoms and other adverse events are seen. In addition, the Food and Drug Administration warned in 2005 that the antipsychotic medications increase mortality among elderly patients. Therefore, new remedies without adverse effects have been sought.Yokukansan (TJ-54) is a traditional herbal medicine called a 'kampo medicine' in Japan. The Ministry of Health, Labor and Welfare in Japan has approved it as a remedy for neurosis, insomnia, and irritability in children. Recently, TJ-54 has been reported to ameliorate excitement, anger, and hallucination in BPSD in patients with Alzheimer's disease, dementia with Lewy bodies, and other forms of senile dementia. 1,2) However, there is limited research on this compound and the mechanism by which it alters the symptoms of dementia is unknown.Up to now, various dementia models including b-amyloid protein precursor (APP) 3) or a-synuclein transgenic mice, 4) and ischemia 5) or scopolamine 6) -treated animals have been used for research in the pathogenesis and therapy of dementia. However, because most studies focused on deficits of the functions of learning and memory that are the main symptoms of dementia, or because only the abnormalities of learning and memory functions are observed in the most models, information regarding BPSD was few in the animal models. Thus, animal models covering peripheral symptoms like BPSD observed in patients with dementia have little been reported. However, recently, it has been reported that not only impairment of learning and memory but also BPSD-like behaviors such as anxiety, depression, muricide, attacking, and startle responses are observed in thiamine-deficient (TD) rats and mice, 7) i.e., the data about BPSD-like behaviors are more abundant than other dementia models. TD is a critical factor in the etiology of Wernicke-Korsakoff's syndrome, which is characterized by a decrease in thiamine pyrophosphate (biologically active form of thiamine)-dependent enzymes involved in cellular glucose and energy metabolism in the brain.8) Thus, although the pathogenesis (or an induction factor) in each dementia model including TD animals is different, there is a common point that memory dysfunction is observed in each model. Furthermore, similar deficiencies in thiamine pyrophosphate-dependent enzyme activities are reported in postmortem brain tissues of patients with Alzheimer's disease. 9) TD has been also reported to induce selective neuronal loss, 10) cholinergic deficits, 11) and accumulations of the abnormal tau isoforms 12) and APP 13) that are involved in Alzheimer's disease. These findings suggest that TD animals may be a valuable tool for evaluation of pharmacotherapy for BPSD as well as dysfunction ...

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Section: Discussionmentioning

confidence: 97%

“…48) In addition, TJ-54 inhibited glutamate-induced PC12 cell death. 48) These results suggest that TJ-54 may exert a neuroprotective effect against the glutamate excitatory neurotoxicity not only by amelioration of dysfunction of astrocytes but also by direct protection of neuronal cells.…”

Section: Discussionmentioning

confidence: 97%

Effects of Yokukansan, a Traditional Japanese Medicine, on Memory Disturbance and Behavioral and Psychological Symptoms of Dementia in Thiamine-Deficient Rats

Ikarashi

Iizuka

Imamura

et al. 2009

Biological & Pharmaceutical Bulletin

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“…Therefore, it is suggested that neuroprotective agents can improve anxiety-like behavior in cerebral ischemic animals. Yokukansan has a neuroprotective effect on glutamate-mediated excitotoxicity in cultured cells [24]. In addition, repeated administration of yokukansan ameliorates hippocampal CA1 neuronal death in rats subjected to repeated cerebral ischemia (unpublished data), suggesting that the anxiolytic effect of yokukansan is mediated partly via a neuroprotective effect.…”

Section: Repeated Ischemia Time Spent In the Dark Box (Sec)mentioning

confidence: 91%

Effects of yokukansan on anxiety-like behavior in a rat model of cerebrovascular dementia

et al. 2010

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Behavioral and psychological symptoms of dementia (BPSD) are commonly seen in patients with dementia. Current pharmacological approaches to treatment are inadequate, despite the availability of serotonergic agents to ameliorate anxiety, one of the symptoms of BPSD. The herbal medicine yokukansan has been demonstrated to improve BPSD in a randomized, single-blinded, placebo-controlled study. However, the mechanisms of the anxiolytic effect of yokukansan have not been clarified. There are also no reports on the anxiolytic effect of yokukansan in cerebrovascular ischemia models. In this study, we examined whether rats subjected to repeated cerebral ischemia exhibited anxiety-like behavior in a plus-maze task, a light/dark box test and an open-field task. We then investigated the effect of yokukansan on anxiety-like behavior in ischemic rats. Repeated ischemia was induced by the four-vessel occlusion method in which a 10-min ischemic episode was repeated once after 60 min. Yokukansan was orally administered once a day for 14 days from 7 days before ischemia induction. The last administration was performed 1 h before the behavioral experiments. The ischemic rats showed anxiety-like behavior in all three tasks, suggesting that this rat may be a good model for anxiety in cerebrovascular dementia. Yokukansan exhibited anxiolytic effects on the anxiety-like behavior in rats subjected to repeated cerebral ischemia, and exerted antagonistic effects on the wet-dog shakes induced by 1-(2,5-dimethoxy-4-indophenyl)-2-amino propane, a serotonin receptor (5-HT(2A)) agonist. This study revealed that yokukansan shows anxiolytic effects not only in normal animals but also in cerebrovascular model rats.

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“…With regard to the 5-HT nervous system, a partial antagonist effect on 5-HT1A receptors [19] and a down regulation effect on 5-HT2A receptors [20] is currently being clarified; with regard to the glutamic acid nervous system, an inhibiting effect on the release of glutamic acid [21], a stimulating effect on glutamic acid transporters [22], and a protective effect on nerve cells [23] are being clarified. KB-83 is obtained by adding dried citrus peel and pinellia tuber to YKS, and is speculated to produce effects that are due to this addition.…”

Section: Discussionmentioning

confidence: 99%

Systematic Review: Effects of the Kampo Formula Yokukan-San-Ka-Chimpi-Hange on Behavioral and Psychological Symptoms of Dementia

Baba¹,

Yakubo²,

Fukuda³

et al. 2017

Altern Integr Med

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Introduction: Randomized usual-case controlled studies on Japanese dementia patients with behavioral and psychological symptoms were conducted to examine the effects of Kampo medicine Yokukan-San (YKS) on the behavioral and psychological symptoms of dementia (BPSD). These studies showed that YKS is effective in treating BPSD. Yokukan-San-Ka-Chimpi-Hange is a Kampo medicine made by adding dried citrus peel and pinellia tuber to YKS. In Japan, we usually administer Yokukan-San-Ka-Chimpi-Hange as Kracie Yokukan-San-Ka-Chimpi-Hange extract granules (KB-83), produced by Kracie Pharma, Ltd. (Tokyo, Japan).

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Neuroprotective effects of yokukansan, a traditional japanese medicine, on glutamate-mediated excitotoxicity in cultured cells

Cited by 97 publications

References 48 publications

Effects of Yokukansan, a Traditional Japanese Medicine, on Memory Disturbance and Behavioral and Psychological Symptoms of Dementia in Thiamine-Deficient Rats

Effects of Yokukansan, a Traditional Japanese Medicine, on Memory Disturbance and Behavioral and Psychological Symptoms of Dementia in Thiamine-Deficient Rats

Effects of yokukansan on anxiety-like behavior in a rat model of cerebrovascular dementia

Systematic Review: Effects of the Kampo Formula Yokukan-San-Ka-Chimpi-Hange on Behavioral and Psychological Symptoms of Dementia

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