Mizoguchi Kazushige, Ikarashi Yasushi
Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura & Co., Ibaraki Japan.
Front Pharmacol. 2017 Mar 21;8:149. doi: 10.3389/fphar.2017.00149. eCollection 2017.
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.
yokukansan（YKS）是一种传统的日本汉方药物，适用于儿童夜啼和易怒，以及神经症和失眠。目前它还用于治疗痴呆症的行为和心理症状（BPSD），如攻击性、激动和幻觉。与临床证据并行，已经进行了大量基础研究以阐明YKS的神经心理药理学功效，迄今为止包括我们自己的研究在内已发表了约70篇文章。最近，我们综述了YKS的神经药理学机制，包括其对谷氨酸能、血清素能和多巴胺能神经传递的影响，以及产生这些作用的成分的药代动力学。本综述旨在整合有关YKS心理药理学作用与已知受影响脑区的信息，以促进我们对YKS临床疗效的理解。在本综述中，我们首先表明YKS具有多种作用，可改善类似于BPSD的症状，如攻击性、幻觉、焦虑和睡眠障碍，以及迟发性运动障碍和认知缺陷等症状。接下来我们提供证据表明YKS可以与包括大脑皮层、海马体、纹状体和脊髓在内的各种脑区相互作用，这些脑区的功能障碍与精神症状、认知缺陷、异常行为和感觉异常有关。此外，YKS的主要活性成分甲基异喹啉和18β-甘草次酸分别主要与额叶皮层和海马体结合。我们的研究结果表明YKS具有多种心理药理学作用，并且这些作用可能是由几个脑区之间的相互作用介导的。在本综述中，我们总结了关于多成分药物YKS对复杂神经网络的宝贵作用的现有信息。
