title: Yokukansan enhances the proliferation of B65 neuroblastoma.
abstract: 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, bothBupleuri RadixandGlycyrrhize Radixalso 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, neitherBupleuri RadixnorGlycyrrhize Radixaltered the level of p44/42 MAPK phosphorylation, although they did increase cell proliferation. Our findings suggest that yokukansan has a cell-proliferative due to bothBupleuri RadixandGlycyrrhize Radix, and this is unrelated to the p44/42 MAPK signaling cascade.
authors.affiliation: Department of Pharmacology, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi, 324-8501, Japan; Department of Pharmacotherapeutics, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi, 324-8501, Japan; Advanced Education and Research Center for Kampo Medicine, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi, 324-8501, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Nakatani
authors.affiliation: Department of Pharmacotherapeutics, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi, 324-8501, Japan; Advanced Education and Research Center for Kampo Medicine, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi, 324-8501, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Amano
authors.affiliation: Department of Molecular and Pharmacological Neuroscience, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Department of Molecular and Pharmacological Neuroscience, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Sakai
authors.affiliation: Department of Pharmacology, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi, 324-8501, Japan; Advanced Education and Research Center for Kampo Medicine, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi, 324-8501, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Tsuji
authors.affiliation: Department of Pharmacology, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi, 324-8501, Japan; Advanced Education and Research Center for Kampo Medicine, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi, 324-8501, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeda
keywords: 5-HT, Serotonin; ALR, Atractylodis lanceae Rhizoma; AR, Angelicae Radix; B65 neuroblastoma; BPSD, Behavioral and psychological symptoms of dementia; BR, Bupleuri Radix; Bupleuri Radix; CR, Cnidii Rhizoma; Cell proliferation; GR, Glycyrrhize Radix; Glycyrrhize Radix; MAPK, Mitogen-activated protein kinase; PR, Poria; SSRI, Selective serotonin reuptake inhibitor; UR, Uncariae Uncis cum Ramulus; Yokukansan