Yokukansan, a traditional Japanese medicine, decreases head-twitch behaviors and serotonin 2A receptors in the prefrontal cortex of isolation-stressed mice

Ueki, Toshiyuki; Mizoguchi, Kazuo; Yamaguchi, Takuji; Nishi, Akinori; Sekiguchi, Kyoji; Ikarashi, Yasushi; Kase, Yoshio

doi:10.1016/j.jep.2015.02.046

Cited by 27 publications

(23 citation statements)

References 53 publications

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“…In normal mice, oral administration of YKS reduced head-twitch behavior induced by treatment with the 5-HT 2A receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) (Egashira et al, 2008). In stressed mice, isolation stress for 6 weeks aggravated the hallucination-like behavior, and YKS reversed this aggravation, which was thought to be mediated by additive and/or synergic effects of Bupleurum root, Uncaria hook, Japanese Angelica root, and Glycyrrhiza in YKS (Ueki et al, 2015b). A similar result was seen in rats subjected to ischemia/reperfusion injury (Nogami et al, 2011).…”

Section: Psychopharmacological Effects Of Yksmentioning

confidence: 99%

“…YKS has been shown to downregulate 5-HT 2A receptor expression in the PFCs and reduce the DOI-induced hallucination-like behavior (head-twitching) in normal mice (Egashira et al, 2008) and stressed mice (Ueki et al, 2015b). It has been suggested that there is a synergistic effect of Bupleurum root, Uncaria hook, Japanese Angelica root, and Glycyrrhiza among seven constituent components of YKS is suggested to be concerned in this downregulation of 5-HT 2A receptors (Ueki et al, 2015b). These results indicate that the reduction of DOI-induced hallucination-like behavior by YKS might involve down-regulation of 5-HT 2A receptors in the PFC.…”

Section: Brain Regions Responsible For the Psychopharmacological Effementioning

confidence: 99%

“…Basic research has also shown the psychopharmacological effects of YKS against BPSD-like symptoms, other neurological symptoms, and cognitive deficits. For example, YKS has been demonstrated to ameliorate aggressiveness (Ikarashi et al, 2009; Iizuka et al, 2010), hallucinations (Egashira et al, 2008; Ueki et al, 2015a,b), anxiety (Mizoguchi et al, 2010b; Shoji and Mizoguchi, 2013), dyskinesia (Sekiguchi et al, 2012), neuropathic pain (Suzuki et al, 2012), and memory impairment (Ikarashi et al, 2009; Tabuchi et al, 2009; Fujiwara et al, 2011; Nogami et al, 2013; Uchida et al, 2013; Liu et al, 2014). …”

Section: Introductionmentioning

confidence: 99%

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Multiple Psychopharmacological Effects of the Traditional Japanese Kampo Medicine Yokukansan, and the Brain Regions it Affects

Mizoguchi

Ikarashi

2017

Front. Pharmacol.

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Yokukansan (YKS), a traditional Japanese Kampo medicine, has indications for use in night crying and irritability in children, as well as neurosis and insomnia. It is currently also used for the remedy of the behavioral and psychological symptoms of dementia (BPSD), such as aggressiveness, agitation, and hallucinations. In parallel with clinical evidence, a significant amount of fundamental researches have been undertaken to clarify the neuropsychopharmacological efficacies of YKS, with approximately 70 articles, including our own, being published to date. Recently, we reviewed the neuropharmacological mechanisms of YKS, including its effects on glutamatergic, serotonergic, and dopaminergic neurotransmission, and pharmacokinetics of the ingredients responsible for the effects. This review is aimed to integrate the information regarding the psychopharmacological effects of YKS with the brain regions known to be affected, to facilitate our understanding of the clinical efficacy of YKS. In this review, we first show that YKS has several effects that act to improve symptoms that are similar to BPSDs, like aggressiveness, hallucinations, anxiety, and sleep disturbance, as well as symptoms like tardive dyskinesia and cognitive deficits. We next provide the evidence showing that YKS can interact with various brain regions, including the cerebral cortex, hippocampus, striatum, and spinal cord, dysfunctions of which are related to psychiatric symptoms, cognitive deficits, abnormal behaviors, and dysesthesia. In addition, the major active ingredients of YKS, geissoschizine methyl ether and 18β-glycyrrhetinic acid, are shown to predominantly bind to the frontal cortex and hippocampus, respectively. Our findings suggest that YKS has multiple psychopharmacological effects, and that these are probably mediated by interactions among several brain regions. In this review, we summarize the available information about the valuable effects of a multicomponent medicine YKS on complex neural networks.

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Section: Psychopharmacological Effects Of Yksmentioning

confidence: 99%

Section: Brain Regions Responsible For the Psychopharmacological Effementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Multiple Psychopharmacological Effects of the Traditional Japanese Kampo Medicine Yokukansan, and the Brain Regions it Affects

Mizoguchi

Ikarashi

2017

Front. Pharmacol.

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“…Ueki et al . reported that isolation stress enhanced the DOI‐induced head‐twitch behaviors and increased 5‐HT 2A receptor density in the prefrontal cortex in mice . Moreover, repeated treatment with YKS reduced the enhancement of head‐twitch behaviors and reduced the increase in 5‐HT 2A receptor density.…”

Section: Behavioral Effectsmentioning

confidence: 95%

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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“…Poria cocos Wolf (Polyporaceae) is a saprophytic fungus that grows on the roots of pine trees in China and other Asian countries. Dried sclerotia of P. cocos, called Fuling, are widely used as a valuable medicine in traditional Chinese prescriptions (Song et al 2011;Kang et al 2015;Ueki et al 2015). In the past decades, researchers from China and Japan have isolated the major known compounds from different parts of P. cocos and extensively investigated their biological activities.…”

Section: Introductionmentioning

confidence: 99%

Antiepileptic activity of total triterpenes isolated fromPoria cocosis mediated by suppression of aspartic and glutamic acids in the brain

Gao

Yan

Jin³

et al. 2016

Pharmaceutical Biology

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Context: Triterpenes from Poria cocos Wolf (Polyporaceae) have been used to treat various diseases in traditional Chinese medicine. However, the antiepileptic effects and mechanism are not fully understood. Objective: The objective of this study is to investigate the antiepileptic properties of total triterpenes (TTP) from the whole P. cocos. Materials and methods: The ethanol extract TTP was identified by HPLC fingerprint analysis. Male ICR mice were gavaged (i.g.) with TTP (5, 20, 80 or 160 mg/kg) or reference drugs twice a day for 7 d. Antiepileptic activities of TTP were evaluated by maximal electroshock (MES)-and pentylenetetrazole (PTZ)-induced seizures in mice for 30 and 60 min, respectively. Locomotor activity and Rota-rod tests were performed for 60 min and 5 min, respectively. The levels of glutamic acid (Glu), aspartic acid (Asp), c-aminobutyric acid (GABA) and glycine (Gly) in convulsive mice were estimated. The chronic epileptic model of Wistar rats was built to measure expressions of glutamate decarboxylase 65 (GAD65) and GABA A in rat brain after TTP treatment. Results: The LC 50 of TTP (i.g.) was above 6 g/kg. TTP (5-160 mg/kg) protected mice against MES-and PTZinduced convulsions at 65.0% and 62.5%, respectively, but have no effect on rota-rod treadmill; TTP (20-160 mg/kg) significantly reduced the locomotor activities, shortened the onset of pentobarbital sodium-induced sleep; TTP decreased Glu and Asp levels in convulsive mice, but increased the GAD65 and GABA A expressions in chronic epileptic rats at doses usage. Discussion and conclusion: TTP extracted from P. cocos possessed potential antiepileptic properties and is a candidate for further antiepileptic drug development. ARTICLE HISTORY

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Yokukansan, a traditional Japanese medicine, decreases head-twitch behaviors and serotonin 2A receptors in the prefrontal cortex of isolation-stressed mice

Cited by 27 publications

References 53 publications

Multiple Psychopharmacological Effects of the Traditional Japanese Kampo Medicine Yokukansan, and the Brain Regions it Affects

Multiple Psychopharmacological Effects of the Traditional Japanese Kampo Medicine Yokukansan, and the Brain Regions it Affects

Pharmacological effects of yokukansan on behavioral and psychological symptoms of dementia

Antiepileptic activity of total triterpenes isolated fromPoria cocosis mediated by suppression of aspartic and glutamic acids in the brain

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