Randomized double‐blind placebo‐controlled multicenter trial of <scp>Y</scp>okukansan for neuropsychiatric symptoms in <scp>A</scp>lzheimer's disease

Furukawa, Koichi; Tomita, Naoki; Uematsu, Daisuke; Okahara, Kazunori; Shimada, Hiroyuki; Ikeda, Masaki; Matsui, Toshifumi; Kozaki, Koichi; Fujii, Masahiko; Ogawa, Takanobu; Umegaki, Hiroyuki; Urakami, Katsuya; Nomura, Hiroshi; Kobayashi, Naho; Nakanishi, A.; Washimi, Yukihiro; Yonezawa, Hisashi; Takahashi, Satoshi; Kubota, Masaharu; Wakutani, Yosuke; Ito, Daisuke; Sasaki, Takahiro; Matsubara, Etsuro; Une, Kaori; Ishiki, Aiko; Yahagi, Yukie; Shoji, Mikio; Sato, Hiroyasu; Terayama, Yasuo; Kuzuya, Masafumi; Araki, Nobuhito; Kodama, M; Yamaguchi, Takuhiro; Arai, Hiroyuki

doi:10.1111/ggi.12696

Cited by 46 publications

(47 citation statements)

References 30 publications

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“…Yokukansan has been used to treat various diseases such as Alzheimer's disease and schizophrenia [6][7][8][9][10]. However, whether or not yokukansan is able to reduce demyelination in the CNS remains unknown.…”

Section: Discussionmentioning

confidence: 99%

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Yokukansan Reduces Cuprizone-Induced Demyelination in the Corpus Callosum Through Anti-inflammatory Effects on Microglia

et al. 2017

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Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). The release of inflammatory cytokines and pro-oxidant molecules from microglia has been shown to play a key role in the pathology of MS. Thus, suppression of microglial cell activation is an attractive therapeutic option. Yokukansan, a traditional Japanese herbal medicine, has been shown to suppress microglial activity in the CNS. However, whether or not yokukansan reduces demyelination observed in the CNS during MS remains unknown. In this study, female C57BL/6 mice were fed a diet containing 0.2% cuprizone (bis-cyclohexanone oxaldihydrazone) to induce demyelination in the corpus callosum. We investigated whether or not yokukansan reduces cuprizone-induced demyelination using immunohistochemical analyses. Furthermore, we examined the in vitro anti-inflammatory effects of yokukansan on LPS-stimulated BV2 cells, a murine microglial cell line. Luxol fast blue staining and immunostaining for myelin basic protein demonstrated that yokukansan reduces demyelination of the corpora callosa of cuprizone-fed mice. In addition, yokukansan significantly decreased the number of activated microglial cells in the corpora callosa of cuprizone-fed mice. Furthermore, treatment with 500 μg/ml yokukansan suppressed the expression of interleukin-1β and inducible nitric-oxide synthase mRNA and protein in LPS-stimulated BV2 cells. These findings suggest that yokukansan reduces demyelination owing to anti-inflammatory effects on microglia. As yokukansan has few adverse effects, yokukansan has the potential to be a novel option to treat MS.

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Section: Discussionmentioning

confidence: 99%

“…Yokukansan, a traditional Japanese herbal medicine, has been reported to have various ameliorative effects on the neurological symptoms of patients with Alzheimer's disease or schizophrenia [6][7][8][9][10]. In both diseases, activated microglia were observed [11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Yokukansan Reduces Cuprizone-Induced Demyelination in the Corpus Callosum Through Anti-inflammatory Effects on Microglia

et al. 2017

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“…Yokukansan has been used to treat neurosis, insomnia, and irritability and/or agitation in infants. It has been reported as effective in improving BPSD in patients with dementia (Iwasaki et al, 2005), and clinical trials regarding its efficacy have been conducted (Furukawa et al, 2015;Okamoto et al, 2014).…”

Section: Methodsmentioning

confidence: 99%

Behavioral and psychological symptoms of dementia in older residents in long-term care facilities in Japan: a cross-sectional study

Arai

Ozaki

Katsumata

2016

Aging & Mental Health

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“…In addition, Furukawa et al . reported in a randomized double‐blind placebo‐controlled multicenter trial that YKS improved some symptoms linked to agitation, aggression, and hallucinations with low frequency of adverse events . This suggests that YKS improves BPSD, including a diverse array of psychiatric symptoms.…”

Section: Introductionmentioning

confidence: 94%

Pharmacological effects of yokukansan on behavioral and psychological symptoms of dementia

Egashira

Iwasaki

2019

Traditional & Kampo Medicine

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Background Cognitive dysfunction is often accompanied by behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimer's disease and other forms of senile dementia. BPSD include agitation, aggression, and hallucinations. BPSD have a serious effect on the quality of life of dementia patients and their caregivers, but effective drug therapy for BPSD has not been identified as yet. Typical and atypical antipsychotics that are used for the treatment of BPSD are known to cause a variety of extrapyramidal adverse events. Yokukansan (YKS, Yi‐gan san in Chinese) is a Japanese traditional herbal (kampo) medicine that is used to alleviate night‐crying and irritation in children, as well as to treat neurosis and insomnia. It is currently also used to treat BPSD. Methods In this review, we summarize the pharmacological effects of YKS in the context of BPSD. Conclusion YKS is expected to be useful in treating and/or preventing BPSD.

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Randomized double‐blind placebo‐controlled multicenter trial of Yokukansan for neuropsychiatric symptoms in Alzheimer's disease

Abstract: Our data did not reach statistical significance regarding the efficacy of YKS against BPSD; however, YKS improves some symptoms including "agitation/aggression" and "hallucinations" with low frequencies of adverse events. Geriatr Gerontol Int 2017; 17: 211-218.

Cited by 46 publications

References 30 publications

Yokukansan Reduces Cuprizone-Induced Demyelination in the Corpus Callosum Through Anti-inflammatory Effects on Microglia

Yokukansan Reduces Cuprizone-Induced Demyelination in the Corpus Callosum Through Anti-inflammatory Effects on Microglia

Behavioral and psychological symptoms of dementia in older residents in long-term care facilities in Japan: a cross-sectional study

Pharmacological effects of yokukansan on behavioral and psychological symptoms of dementia

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