An exploratory study of the efficacy and safety of yokukansan for neuropsychiatric symptoms in patients with Parkinson’s disease

Hatano, Taku; Hattori, Nobutaka; Kawanabe, Tadaaki; Terayama, Yasuo; Suzuki, Noriyuki; Iwasaki, Yasuo; Fujioka, Toshiki

doi:10.1007/s00702-013-1105-y

Cited by 28 publications

(24 citation statements)

References 26 publications

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“…In addition, YKS improved BPSD such as hallucination, agitation, aggressiveness, and anxiety in patients with AD, [1][2][3] DLB, 4,5) PD, or PDD. 6,7) Reduced dopaminergic activity in the striatum and PFC in 6-OHDA-lesioned rats caused anxiogenic responses in the elevated plus-maze test, 49) whereas decreased DA levels in the medial PFC increased anxiety induced by social defeat stress. 50) Reduced PFC dopaminergic function or the blockade of DA receptors in the PFC impaired working memory.…”

Section: Discussionmentioning

confidence: 99%

“…It has been approved by the Japanese Ministry of Health, Labour and Welfare as a treatment for neurosis, insomnia, and irritability in children. Recently, YKS was reported to reduce the behavioral and psychological symptoms of dementia (BPSD), including agitation, aggressiveness, and hallucinations, not only in patients with Alzheimer's disease (AD) [1][2][3] but also in those with dementia with Lewy bodies (DLB), 4,5) Parkinson's disease (PD), or PD with dementia (PDD), 6,7) which are characterized by progressive dopamine (DA) neuronal loss. These clinical findings suggested that YKS acts on the DA nerve system, but it does not show the extrapyramidal side effects of the typical or atypical antipsychotic drugs used in the treatment of BPSD, which have a DA D 2 receptor antagonistic effect.…”

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confidence: 99%

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Yokukansan, a Traditional Japanese Medicine, Enhances the L-DOPA-Induced Rotational Response in 6-Hydroxydopamine-Lesioned Rats: Possible Inhibition of COMT

Ishida

Ebihara

Tabuchi

et al. 2016

Biological & Pharmaceutical Bulletin

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The aim of the present study was to investigate the effects of the traditional Japanese medicine yokukansan (YKS) on the function of dopamine (DA) in the rat nigrostriatal system. Unilateral 6-hydroxydopamine lesions were produced in the rat nigrostriatal system. Despite a marked loss in the striatal immunoreactivity of tyrosine hydroxylase on the lesion side, striatal serotonin (5-HT) immunoreactivity was not affected. Treatment using L-3,4-dihydroxyphenylalanine (L-DOPA) in conjunction with benserazide for 15 d induced abnormal involuntary movements (AIMs) such as locomotive (rotational response), axial, forelimb, and orolingual movements in the lesioned rats. The L-DOPA-induced locomotive and axial, but not forelimb and orolingual, AIMs were significantly increased and prolonged by the pre-administration of YKS. We next investigated

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Yokukansan, a Traditional Japanese Medicine, Enhances the L-DOPA-Induced Rotational Response in 6-Hydroxydopamine-Lesioned Rats: Possible Inhibition of COMT

Ishida

Ebihara

Tabuchi

et al. 2016

Biological & Pharmaceutical Bulletin

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“…Several clinical studies have shown that the administration of yokukansan could ameliorate the symptoms of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease 2, 3. Moreover, yokukansan could also improve neuropsychiatric symptoms associated with Parkinson's diseases, including hallucinations, anxiety and apathy without severe adverse events or worsening of Parkinsonism 4 . According to the clinical studies of yokukansan mentioned above, yokukansan may have multiple components that are effective at treating various central nervous system diseases.…”

Section: Introductionmentioning

confidence: 99%

Yokukansan enhances the proliferation of B65 neuroblastoma

Nakatani

Amano

Yamamoto

et al. 2017

Journal of Traditional and Complementary Medicine

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Yokukansan, a traditional Japanese herbal medicine, has been considered to be a novel alternative treatment for several neurological diseases such as neurodegenerative disorders, as well as neurosis, insomnia, and behavioral and psychological symptoms in Alzheimer's disease. Moreover, it has been shown that yokukansan has antidepressant-like and pain-relieving effects in animal models. Recently, several studies have shown that yokukansan has a neuroprotective effect. In this study, we focused on whether or no yokukansan influences cell proliferation related to cell-cycle progression by using B65 neuroblastoma cells derived from monoaminergic neurons. Under treatment with yokukansan, the proliferation rate of B65 neuroblastoma cells significantly increased in a dose-dependent manner. In particular, a proliferative effect was observed after treatment with yokukansan for 48 h and 72 h. Moreover, among seven medicinal herbs that comprise yokukansan, both Bupleuri Radix and Glycyrrhize Radix also enhanced the proliferation of B65 neuroblastoma cells. We assessed the effect of yokukansan on p44/42 mitogen-activated protein kinase (MAPK) phosphorylation in B65 neuroblastoma cells, and found that yokukansan increased p44/42 MAPK phosphorylation after treatment for 48 h. In contrast, neither Bupleuri Radix nor Glycyrrhize Radix altered the level of p44/42 MAPK phosphorylation, although they did increase cell proliferation. Our findings suggest that yokukansan has a cell-proliferative due to both Bupleuri Radix and Glycyrrhize Radix, and this is unrelated to the p44/42 MAPK signaling cascade.

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“…Uncaria hook has been traditionally used for the treatment of hypertension, dizziness, and stroke. Recently, YKS was reported to improve behavioral and psychological symptoms of dementia such as hallucinations, agitation, and aggressiveness in patients with Alzheimer’s disease, Parkinson’s disease and dementia (Hatano et al, 2014; Mizukami et al, 2009; Okahara et al, 2010). It shows protective effects against neuronal cell death induced by glutamate-mediated oxidative stress, and Uncaria hook was found to have the highest potency in the protection (Kawakami et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Geissoschizine methyl ether protects oxidative stress-mediated cytotoxicity in neurons through the ‘Neuronal Warburg Effect’

Sun

Ren

et al. 2016

Journal of Ethnopharmacology

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Ethnopharmacological relevance The rate of production of reactive oxygen species (ROS) is determined by mitochondrial metabolic rate. In turn, excessive ROS damage mitochondrial function, which is linked to aging and neurodegenerative conditions. One possible path to prevent oxidative stress could be achieved by reducing mitochondrial respiration in favor of less efficient ATP production via glycolysis. Such a shift in energy metabolism is known as the ‘Warburg effect’. Geissoschizine methyl ether (GM) is one of the active components responsible for the psychotropic effects of Yokukansan, an herbal preparation widely used in China and Japan. Aim of the study GM protects neurons from glutamate-induced oxidative cytotoxicity through regulating mitochondrial function and suppressing ROS generation. We investigated the protective mechanism of GM against glutamate-induced oxidative stress in neuronal cells. Materials and methods The current study was performed on primary neurons and HT22 cells, a hippocampus neuronal cell line. Cell viability was measured by Calcein AM assay. H2DCFDA staining was used for intracellular ROS measurement. GSH level was measured using the GSH-Glo™ luminescence-based assay. Mitochondrial respiration and glycolysis were measured by the Seahorse Bioscience XFe 96 Extracellular Flux Analyzer. Protein levels were analyzed by western blot analysis. Results GM prevented glutamate-induced cytotoxicity in an HT-22 neuronal cell line even with a 9-hour exposure delay. GM blocked glutamate-induced intracellular ROS accumulation through suppressing mitochondrial respiration. Further, we found that GM up-regulated glycolysis and the pentose-phosphate pathway, which is involved in the production of intracellular reducing agent, NADPH. In addition, GM protected primary cortical neurons from both glutamate and buthioninesulfoximine toxicity. Conclusion GM prevents glutamate-induced oxidative damage through reducing mitochondrial respiration, which further suppresses ROS generation. In addition, GM up-regulates glycolysis which compensate for the energy depletion induced by mitochondrial respiration inhibition. Overall, our study is the first to report that GM protects neurons from oxidative toxicity by shifting energy metabolism from mitochondrial respiration to glycolysis.

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An exploratory study of the efficacy and safety of yokukansan for neuropsychiatric symptoms in patients with Parkinson’s disease

Cited by 28 publications

References 26 publications

Yokukansan, a Traditional Japanese Medicine, Enhances the L-DOPA-Induced Rotational Response in 6-Hydroxydopamine-Lesioned Rats: Possible Inhibition of COMT

Yokukansan, a Traditional Japanese Medicine, Enhances the L-DOPA-Induced Rotational Response in 6-Hydroxydopamine-Lesioned Rats: Possible Inhibition of COMT

Yokukansan enhances the proliferation of B65 neuroblastoma

Geissoschizine methyl ether protects oxidative stress-mediated cytotoxicity in neurons through the ‘Neuronal Warburg Effect’

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