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

Kazushige Mizoguchi,Yasushi Ikarashi

doi:10.3389/fphar.2017.00149

Kazushige Mizoguchi, Yasushi Ikarashi

Open Access

https://doi.org/10.3389/fphar.2017.00149

Copy DOI

Abstract

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.

Highlights

The traditional Japanese Kampo medicine Yokukansan (YKS) has been approved by the Japanese Ministry of Health, Labor, and Welfare, and has indication for neurosis, insomnia, and children’s night crying and irritability
Dementia is often complicated by behavioral and psychological symptoms of dementia (BPSD), and many clinical trials have shown the usefulness of YKS for the treatment of related aggressiveness, agitation, and hallucination, without producing severe side effects
We described the multiple psychopharmacological effects of YKS, including the ameliorative effects on aggressiveness, hallucination, anxiety, sleep disturbance, hyperlocomotion, maladaptation, reduced prepulse inhibition (PPI), tardive dyskinesia, neuropathic pain, morphine dependence, allergy/atopic dermatitis, and cognitive dysfunction in experimental animals

Summary

Introduction

The traditional Japanese Kampo medicine Yokukansan (YKS) has been approved by the Japanese Ministry of Health, Labor, and Welfare, and has indication for neurosis, insomnia, and children’s night crying and irritability In recent year, this remedy has been used for treating the behavioral and psychological symptoms of dementia (BPSD), such as aggressiveness and hallucinations, Yokukansan Has Multiple Psychopharmacological Actions which are frequently observed in patients with Alzheimer’s disease, dementia with Lewy body, vascular dementia, and so on, without a serious side effect (Iwasaki et al, 2005; Mizukami et al, 2009; Monji et al, 2009; Okahara et al, 2010; Nagata et al, 2012; Matsuda et al, 2013). 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)

Objectives

Methods

Findings

Conclusion