title: Ameliorating effect of Yokukansan on the development of atopic dermatitis-like lesions and scratching behavior in socially isolated NC/Nga mice.
abstract: Yokukansan (YKS) has been used in Japan as a remedy for neurosis, insomnia, and children with night crying. In a previous study, we reported that YKS controls scratching behavior and inhibits the development of atopic dermatitis (AD)-like lesions in NC/Nga mice. In this study, we investigated the effects of YKS on the development of AD-like lesions in socially isolated NC/Nga mice compared with the effects of fexofenadine and elucidated the mechanism of the ameliorating effect of YKS on the skin lesions. Ten-week-old male NC/Nga mice were divided into three groups (n = 5/group): the conventional control, the YKS-treated, and the fexofenadine-treated groups, and were kept isolated under conventional conditions for 6 weeks. Measurements were made of dermatitis scores and transepidermal water loss (TEWL), scratching and grooming behaviors. Immunohistochemistry and mRNA levels were also evaluated. We performed similar experiments under specific pathogen free (SPF) conditions that served as a SPF control. YKS and fexofenadine inhibited the aggravation of skin lesions and decreased TEWL, but only YKS decreased the numbers of scratching and pathologic grooming behaviors. Immunohistochemistry and RT-PCR revealed that N-methyl-D: -aspartate (NMDA) receptor expression was increased in the skin of conventional control mice and was decreased in YKS-treated mice. Glutamate transporter-1 (GLT-1) mRNA levels were decreased in the skin of conventional control mice and were increased in YKS-treated mice. The results indicate that YKS ameliorates AD-like skin lesions in NC/Nga mice through a mechanism distinct from that of fexofenadine. Furthermore, the effects of YKS are suggested to be mediated via glutamate signaling in the skin lesions.
authors.affiliation: Department of Dermatology, Juntendo University School of Medicine, Hongo, Bunkyo-ku, Tokyo, Japan. nao2794@juntendo.ac.jp
authors.forename: Naoko
authors.initials: N
authors.lastname: Funakushi
authors.forename: Takuji
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Ju
authors.initials: J
authors.lastname: Jiang
authors.forename: Sachiko
authors.initials: S
authors.lastname: Imamura
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Kuhara
authors.forename: Hajime
authors.initials: H
authors.lastname: Suto
authors.forename: Rie
authors.initials: R
authors.lastname: Ueki
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kase
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Hideoki
authors.initials: H
authors.lastname: Ogawa
authors.forename: Shigaku
authors.initials: S
authors.lastname: Ikeda
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage* / Q000009:adverse effects; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000503:physiopathology; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage* / Q000009:adverse effects; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D039563:Histamine H1 Antagonists, Non-Sedating / Q000008:administration & dosage / Q000009:adverse effects; D007150:Immunohistochemistry; D008297:Male; D020835:Medicine, Kampo; D051379:Mice; D008815:Mice, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D012737:Sex Factors; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000187:drug effects* / Q000473:pathology; D012934:Social Isolation; D016593:Terfenadine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives
chemical_list: D014151:Anti-Anxiety Agents; D004365:Drugs, Chinese Herbal; D027342:Excitatory Amino Acid Transporter 2; D039563:Histamine H1 Antagonists, Non-Sedating; D016194:Receptors, N-Methyl-D-Aspartate; C524644:Yi-Gan San; D016593:Terfenadine; C093230:fexofenadine