title: Neuropharmacological efficacy of the traditional Japanese Kampo medicine yokukansan and its active ingredients.
abstract: Dementia is a progressive neurodegenerative disorder with cognitive dysfunction, and is often complicated by behavioral and psychological symptoms of dementia (BPSD) including excitement, aggression, and hallucinations. Typical and atypical antipsychotics are used for the treatment of BPSD, but induce adverse events. The traditional Japanese Kampo medicine yokukansan (YKS), which had been originated from the traditional Chinese medicine Yi-Gan-San, has been reported to improve BPSD without severe adverse effects. In the preclinical basic studies, there are over 70 research articles indicating the neuropharmacological efficacies of YKS. In this review, we first describe the neuropharmacological actions of YKS and its bioactive ingredients. Multiple potential actions for YKS were identified, which include effects on serotonergic, glutamatergic, cholinergic, dopaminergic, adrenergic, and GABAergic neurotransmissions as well as neuroprotection, anti-stress effect, promotion of neuroplasticity, and anti-inflammatory effect. Geissoschizine methyl ether (GM) in Uncaria hook and 18β-glycyrrhetinic acid (GA) in Glycyrrhiza were responsible for several pharmacological actions of YKS. Subsequently, we describe the pharmacokinetics of GM and GA in rats. These ingredients were absorbed into the blood, crossed the blood-brain barrier, and reached the brain, in rats orally administered YKS. Moreover, autoradiography showed that [(3)H]GM predominantly distributed in the frontal cortex and [(3)H]GA in the hippocampus. Thus, YKS is a versatile herbal remedy with a variety of neuropharmacological effects, and may operate as a multicomponent drug including various active ingredients.
authors.affiliation: Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan. Electronic address: ikarashi_yasushi@mail.tsumura.co.jp.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ikarashi
authors.affiliation: Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan. Electronic address: mizoguchi_kazushige@mail.tsumura.co.jp.
authors.forename: Kazushige
authors.initials: K
authors.lastname: Mizoguchi
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism; D003704:Dementia / Q000188:drug therapy*; D004365:Drugs, Chinese Herbal / Q000493:pharmacokinetics / Q000494:pharmacology*; D004721:Endoplasmic Reticulum / Q000473:pathology; D018698:Glutamic Acid / Q000378:metabolism; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D026121:Indole Alkaloids / Q000493:pharmacokinetics / Q000494:pharmacology*; D007249:Inflammation / Q000378:metabolism; D020835:Medicine, Kampo; D051381:Rats; D011985:Receptors, Serotonin / Q000378:metabolism; D032070:Uncaria; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D002395:Catecholamines; D004365:Drugs, Chinese Herbal; D026121:Indole Alkaloids; D011985:Receptors, Serotonin; C524644:Yi-Gan San; C110832:geissoschizine methylether; C119129:18alpha-glycyrrhetinic acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D006034:Glycyrrhetinic Acid
keywords: 18β-Glycyrrhetinic acid; Behavioral and psychological symptoms of dementia; Dementia; Geissoschizine methyl ether; Neuropharmacology; Yokukansan