Yokukansan Enhances Pentobarbital-Induced Sleep in Socially Isolated Mice: Possible Involvement of GABAA – Benzodiazepine Receptor Complex

Egashira, Nobuaki; Nogami, Ai; Iwasaki, Katsunori; Ishibashi, Ayumi; Uchida, Naoki; Takasaki, Kotaro; Mishima, Kenichi; Nishimura, Ryoji; Oishi, Ryozo; Fujiwara, Michihiro

doi:10.1254/jphs.11079sc

Cited by 38 publications

(30 citation statements)

References 14 publications

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“…This effect of YKS may be involved in extracellular glutamate level and GLT1(glutamate transporter 1) messenger RNA expression in the striatum. YKS has a reversal effect on the decrease in pentobarbital sleep by social isolation without affecting pentobarbital sleep in group-housed mice 58. This prolongation of sleeping time in socially isolated mice is reversed by bicuculline, a competitive antagonist of GABA A receptors, and flumazenil, a benzodiazepine receptor antagonist, but not WAY100635, a 5-HT 1A receptor antagonist.…”

Section: Animal Studiesmentioning

confidence: 90%

Yokukan-san: a review of the evidence for use of this Kampo herbal formula in dementia and psychiatric conditions

Okamoto¹,

Iyo²,

Ueda³

et al. 2014

NDT

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Japanese traditional herbal medicine (Kampo) has its origins in traditional Chinese medicine (TCM). It was introduced to Japan in the middle of the sixth century and has evolved over the past 1,400 years after combining with Japan’s original folk remedies. While it retains some similarities to TCM, Kampo has evolved in Japan, resulting in a system of medicine that has many differences from TCM. Kampo medicine is considered to be very safe; in Japan, Kampo herbal formulas are manufactured by licensed pharmaceutical companies, prescribed by Western-trained medical doctors (usually as a freeze-dried extract), and have quality control standards similar to those of prescription drugs. The present study examined Yokukan-san (Yi-Gan San in TCM), a Kampo formula that has been used empirically in Japan for more than 400 years. Accumulating clinical trials have demonstrated Yokukan-san’s efficacy in treating patients with behavioral and psychological symptoms of dementia, which has resulted in the Japanese Society of Neurology listing it in the Japanese Guidelines for the Management of Dementia 2010. Efficacy in other diseases and conditions, such as sleep disorders, tardive dyskinesia, aggression, and impulsivity has also been reported. This article reviews both clinical and basic studies of Yokukan-san, with the goal of clarifying its clinical indications.

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Section: Animal Studiesmentioning

confidence: 90%

Yokukan-san: a review of the evidence for use of this Kampo herbal formula in dementia and psychiatric conditions

Okamoto¹,

Iyo²,

Ueda³

et al. 2014

NDT

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“…YKS has been reported to have antistress,14,15 anxiolytic,27 and antihallucinatory effects 28. Furthermore, it ameliorates sleep disorders24,25 and cognitive dysfunctions;29 acts as a neuroprotective agent,30 and induces neuronal differentiation 31. YKS is also an analgesic21,22,32 that prevents the development of morphine tolerance,33 and it acts as an antipruritic34 and inhibits allergic responses34 and dyskinesia 23…”

Section: Discussionmentioning

confidence: 99%

“…The dose was determined according to the results of previous studies that administered YKS in the range of 50 mg/kg per day to 1,000 mg/kg per day,11–15,20–25 depending on the experimental model and animal species. Uchida et al,11 reported a stress load consistent with that of the current study and that 300 mg/kg of YKS was effective.…”

Section: Discussionmentioning

confidence: 99%

Antistress effects of Kampo medicine "Yokukansan" via regulation of orexin secretion

Katahira¹,

Sunagawa²,

Watanabe

et al. 2017

NDT

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ObjectiveVarious stressors induce stress responses through the hypothalamic–pituitary–adrenal and the sympathetic–adrenal–medullary axes, which are regulated, in part, by orexin. For example, secretion of orexin in the hypothalamus is increased in rats exposed to the stress of social isolation for 1 week. In this study, the antistress effects of Kampo medicine Yokukansan (YKS) via the regulation of orexin secretion were investigated using a rat model.Methods and resultsThe administration of 300 mg/kg per day of YKS to rats for 1 week significantly decreased the plasma orexin levels compared with non-treated rats, whereas the administration of 1,000 mg/kg of YKS had no effect on orexin levels. Therefore, 300 mg/kg of YKS was an effective dose for controlling orexin secretion. Subsequently, rats were divided into group-housed control (Con), individually housed stress (Stress), and individually housed YKS (300 mg/kg)-treated stress (Stress + YKS) groups. After 1 week, a resident–intruder aggression test was performed, and the plasma levels of orexin and corticosterone were measured. In the Stress group, aggressive behavior and the levels of corticosterone and orexin significantly increased compared with the Con group; however, these effects were inhibited in the Stress + YKS group. Further, an orexin receptor antagonist (TCS 1102; 10 mg/kg) was intraperitoneally administered to rats exposed to isolation stress to determine whether orexin was involved in stress responses. Under these conditions, aggressive behavior and the level of corticosterone significantly decreased compared with the Stress group.ConclusionThese results suggest that orexin is involved in the control of stress response and that YKS exerts an antistress effect via the regulation of orexin secretion.

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“…In addition, YKS has a neuroprotective effect against glutamateinduced cytotoxicity through the blockade of N-methyl-D-aspartate receptors and the amelioration of glutamate transporter dysfunction in astrocytes Kawakami et al, 2009Kawakami et al, , 2010Kawakami et al, , 2011. YSK also reverses the social isolation-induced decrease in pentobarbital-mediated sleep by activation of the c-aminobutyric acid A /benzodiazepine receptor complex (Egashira et al, 2011). Thus, YKS exerts its palliative actions by acting on multiple neurotransmitter systems.…”

Section: Introductionmentioning

confidence: 99%

Yokukansan inhibits morphine tolerance and physical dependence in mice: The role of α2A-adrenoceptor

et al. 2012

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Yokukansan Enhances Pentobarbital-Induced Sleep in Socially Isolated Mice: Possible Involvement of GABAA – Benzodiazepine Receptor Complex

Cited by 38 publications

References 14 publications

Yokukan-san: a review of the evidence for use of this Kampo herbal formula in dementia and psychiatric conditions

Yokukan-san: a review of the evidence for use of this Kampo herbal formula in dementia and psychiatric conditions

Antistress effects of Kampo medicine "Yokukansan" via regulation of orexin secretion

Yokukansan inhibits morphine tolerance and physical dependence in mice: The role of α2A-adrenoceptor

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Yokukansan Enhances Pentobarbital-Induced Sleep in Socially Isolated Mice: Possible Involvement of GABAA – Benzodiazepine Receptor Complex

Cited by 38 publications

References 14 publications

Yokukan-san: a review of the evidence for use of this Kampo herbal formula in dementia and psychiatric conditions

Yokukan-san: a review of the evidence for use of this Kampo herbal formula in dementia and psychiatric conditions

Antistress effects of Kampo medicine &quot;Yokukansan&quot; via regulation of orexin secretion

Yokukansan inhibits morphine tolerance and physical dependence in mice: The role of α2A-adrenoceptor

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Antistress effects of Kampo medicine "Yokukansan" via regulation of orexin secretion