The Efficacy and Safety of Yokukansankachimpihange for Treating Behavioral and Psychological Symptoms of Dementia in Patients with Alzheimer’s Disease: An Open-Label Pilot Study

Arita, Ryutaro; Yoshino, Tetsuhiro; Ohgishi, Miwako; Hamaguchi, Takuya; Horiba, Yuko; Sawai, Kaori; Funaki, Kei; Tabuchi, Hajime; Oka, Mutsuo; Yoshizaki, Takahito; Watanabe, Kenji; Mimura, Masaru

doi:10.4236/aad.2018.74010

Cited by 5 publications

(2 citation statements)

References 33 publications

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“…In addition to traditional use, YKSCH has been approved for administration to patients with dementia in Japan to treat behavioral and psychological symptoms of dementia (BPSD). A recent clinical trial revealed that YKSCH treatment improves the Neuropsychiatric Inventory scores of "agitation, " "delusion, " and "sleep and night-time behavior change" in patients with Alzheimer's disease (1). Other research revealed that a combination treatment of YKSCH with donepezil improved diurnal rhythm in patients with Alzheimer's disease (2).…”

Section: Introductionmentioning

confidence: 99%

Yokukansankachimpihange Improves the Social Isolation-Induced Sleep Disruption and Allopregnanolone Reduction in Mice

Murata¹,

Li²,

Shinguchi³

et al. 2020

Front. Nutr.

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Yokukansankachimpihange (YKSCH), a traditional Japanese medicine composed of 9 crude drugs, is designed to improve neurosis, insomnia in adults, and night crying in children. YKSCH has been reported to improve diurnal rhythm in patients with Alzheimer's disease and prolong the total sleeping time in healthy subjects. However, little is known about how YKSCH alleviates sleep disorders. Here, we investigated whether and how YKSCH treatment affected sleep latency and duration in group-housed and socially isolated mice. Male ddy mice were treated with YKSCH [1,500 mg/kg, per os (p.o.)] in group-housed or socially isolated conditions for 3-4 weeks. After the last injection, mice were intraperitoneally (i.p.) administered with pentobarbital (60 mg/kg) and the sleep latency and duration was evaluated. The results show that pretreatment with YKSCH had no effect on sleep latency or duration in group-housed mice. However, YKSCH treatment significantly improved the reduced sleep duration in socially isolated mice. This effect of YKSCH was inhibited by the administration of bicuculline (3 mg/kg, i.p.), a GABA A receptor antagonist. Furthermore, we showed that YKSCH treatment improved the decrease in allopregnanolone content and its synthase expression levels in the olfactory bulb. These results suggest that YKSCH treatment improved social isolation stress-induced insomnia via the GABAergic pathway and that the mechanism of action of YKSCH is partly due to improvement of allopregnanolone levels of expression.

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Section: Introductionmentioning

confidence: 99%

Yokukansankachimpihange Improves the Social Isolation-Induced Sleep Disruption and Allopregnanolone Reduction in Mice

Murata¹,

Li²,

Shinguchi³

et al. 2020

Front. Nutr.

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show abstract

“…A recent observational study showed that a combination of donepezil and YKSCH that contains Citrus reticulata instead of CPU significantly improved BPSD in patients with Alzheimer's disease, in which diurnal rhythm disturbance was significantly improved [27]. More recently, an open-label trial revealed that YKSCH tended to improve BPSD with significant improvement of apathy in Alzheimer's patients [28]. In animals, YKS and YKSCH produced the same degree of improvement in neuropsychiatric and gastrointestinal symptoms in TD rats [29].…”

Section: Introductionmentioning

confidence: 99%

Comparison of the Effects of Yokukansan and Yokukansankachimpihange on Glutamate Uptake by Cultured Astrocytes and Glutamate-Induced Excitotoxicity in Cultured PC12 Cells

Kawakami

Omiya

Mizoguchi

2019

Evidence-Based Complementary and Alternative Medicine

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The traditional Japanese Kampo medicine yokukansan (YKS) is effective for behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimer’s disease. As the pharmacological mechanisms, YKS is known to protect astrocytes from thiamine-deficiency (TD)-induced decreased glutamate (Glu) uptake and neuron model cells (PC 12 cells) from Glu-induced death. Yokukansankachimpihange (YKSCH) is an alternative formula to YKS, in which Citrus unshiu peel and Pinellia tuber are added to the YKS components, and is sometimes used to treat BPSD, but its pharmacological properties remain unknown. This study aims to investigate the cellular pharmacological effects of YKS and YKSCH on glutamatergic pathways, compare their efficacy, and determine the differences and similarities in the activities between these formulations. First, we examined the effects of YKS and YKSCH on Glu uptake by cultured astrocytes under TD conditions. We observed significant ameliorative effects of YKS and YKSCH on the TD-induced decrease in Glu uptake, with a 50% effective dose of 8.9 ± 1.8 μg/mL and 45.3 ± 9.2 μg/mL, respectively. Second, using cultured PC12 cells as a model for neurons, we examined the effects of YKS and YKSCH on Glu-induced cell death. We observed that YKS and YKSCH had significant inhibitory effects on Glu-induced cell death, with a 30% effective dose of 51.4 ± 20.8 μg/mL and 49.2 ± 11.0 μg/mL, respectively. Thus, while YKSCH was less effective than YKS in ameliorating the TD-induced decrease in Glu uptake by astrocytes, the two drugs showed similar inhibitory effects on Glu-induced PC12 cell death. These findings are important for understanding the differences and similarities in pharmacological actions between these drugs.

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Yokukansankachimpihange, a traditional Japanese (Kampo) medicine, enhances the adaptation to circadian rhythm disruption by increasing endogenous melatonin levels

Imamura

Tabuchi

Oizumi

et al. 2020

Journal of Pharmacological Sciences

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The Efficacy and Safety of Yokukansankachimpihange for Treating Behavioral and Psychological Symptoms of Dementia in Patients with Alzheimer’s Disease: An Open-Label Pilot Study

Cited by 5 publications

References 33 publications

Yokukansankachimpihange Improves the Social Isolation-Induced Sleep Disruption and Allopregnanolone Reduction in Mice

Yokukansankachimpihange Improves the Social Isolation-Induced Sleep Disruption and Allopregnanolone Reduction in Mice

Comparison of the Effects of Yokukansan and Yokukansankachimpihange on Glutamate Uptake by Cultured Astrocytes and Glutamate-Induced Excitotoxicity in Cultured PC12 Cells

Yokukansankachimpihange, a traditional Japanese (Kampo) medicine, enhances the adaptation to circadian rhythm disruption by increasing endogenous melatonin levels

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