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Ameliorating effect of Yokukansan on the development of atopic dermatitis-like lesions and scratching behavior in socially isolated NC/Nga mice.

Funakushi N, Yamaguchi T, Jiang J, Imamura S, Kuhara T, Suto H, Ueki R, Kase Y, Kobayashi H, Ogawa H, Ikeda S - Arch. Dermatol. Res. (2011)

Bottom Line: Yokukansan (YKS) has been used in Japan as a remedy for neurosis, insomnia, and children with night crying.YKS and fexofenadine inhibited the aggravation of skin lesions and decreased TEWL, but only YKS decreased the numbers of scratching and pathologic grooming behaviors.Furthermore, the effects of YKS are suggested to be mediated via glutamate signaling in the skin lesions.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, Juntendo University School of Medicine, Hongo, Bunkyo-ku, Tokyo, Japan. nao2794@juntendo.ac.jp

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.

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The effects of YKS and fexofenadine on dermatitis score (a), TEWL (b), the numbers of scratching behaviors (c) and grooming behaviors (d) for AD-like skin lesions in NC/Nga mice. a The skin lesions of the conventional control group were aggravated as time goes on. Both the YKS- and the fexofenadine-treated groups significantly inhibited the aggravation of skin lesions in NC/Nga mice from 3 weeks after the start of the experiments. The dermatitis score of the SPF control group was not more than a minor increase. b The TEWL of the conventional control group was increased as time goes on. The YKS- and the fexofenadine-treated groups significantly inhibited the increase of TEWL compared with the conventional control mice from 3 weeks. The TEWL of the SPF group, which had no skin lesions, was not increased. c Scratching behaviors of the conventional control and the fexofenadine-treated groups increased as time goes on. The YKS-treated group significantly decreased the scratching behaviors compared with the conventional control group after 6 weeks. The scratching behaviors of the SPF group were not increased. d Grooming behaviors of the conventional control group and also the fexofenadine-treated group were increased under social isolated conditions. The YKS-treated group significantly decreased the grooming behaviors compared with the conventional control mice from 3 weeks. The grooming behaviors of the SPF group increased under social isolated conditions. SPF control: unfilled circle, conventional control: filled circle, YKS: filled square, fexofenadine: filled triangle. Data are presented as means ± SE (n = 5–6). †p < 0.05, ††p < 0.01 vsersu SPF control, *p < 0.05, **p < 0.01 versus conventional control, one-way ANOVA followed by Bonferroni/Dunn test
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Fig1: The effects of YKS and fexofenadine on dermatitis score (a), TEWL (b), the numbers of scratching behaviors (c) and grooming behaviors (d) for AD-like skin lesions in NC/Nga mice. a The skin lesions of the conventional control group were aggravated as time goes on. Both the YKS- and the fexofenadine-treated groups significantly inhibited the aggravation of skin lesions in NC/Nga mice from 3 weeks after the start of the experiments. The dermatitis score of the SPF control group was not more than a minor increase. b The TEWL of the conventional control group was increased as time goes on. The YKS- and the fexofenadine-treated groups significantly inhibited the increase of TEWL compared with the conventional control mice from 3 weeks. The TEWL of the SPF group, which had no skin lesions, was not increased. c Scratching behaviors of the conventional control and the fexofenadine-treated groups increased as time goes on. The YKS-treated group significantly decreased the scratching behaviors compared with the conventional control group after 6 weeks. The scratching behaviors of the SPF group were not increased. d Grooming behaviors of the conventional control group and also the fexofenadine-treated group were increased under social isolated conditions. The YKS-treated group significantly decreased the grooming behaviors compared with the conventional control mice from 3 weeks. The grooming behaviors of the SPF group increased under social isolated conditions. SPF control: unfilled circle, conventional control: filled circle, YKS: filled square, fexofenadine: filled triangle. Data are presented as means ± SE (n = 5–6). †p < 0.05, ††p < 0.01 vsersu SPF control, *p < 0.05, **p < 0.01 versus conventional control, one-way ANOVA followed by Bonferroni/Dunn test

Mentions: Dermatitis scores of the conventional control group were aggravated as time goes on. Both the YKS- and the fexofenadine-treated groups significantly inhibited the aggravation of skin lesions in NC/Nga mice from 3 weeks after the start of the experiments. The dermatitis score of the SPF control group was not more than a minor increase (Fig. 1a). The TEWL of the conventional control group was increased as time goes on. The YKS- and the fexofenadine-treated groups significantly inhibited the increase of TEWL compared with the conventional control mice from 3 weeks. The TEWL of the SPF group, which had no skin lesions, was not increased (Fig. 1b). Scratching behaviors of the conventional control and the fexofenadine-treated groups increased as time goes on. The YKS-treated group significantly decreased the scratching behaviors compared with the conventional control group after 6 weeks. The scratching behaviors of the SPF group was not increased (Fig. 1c). Grooming behaviors of the conventional control group and the fexofenadine-treated group were increased under social isolated conditions. The YKS-treated group significantly decreased the grooming behaviors compared to the conventional control mice from 3 weeks. The grooming behaviors of the SPF group increased under social isolated conditions (Fig. 1d).Fig. 1


Ameliorating effect of Yokukansan on the development of atopic dermatitis-like lesions and scratching behavior in socially isolated NC/Nga mice.

Funakushi N, Yamaguchi T, Jiang J, Imamura S, Kuhara T, Suto H, Ueki R, Kase Y, Kobayashi H, Ogawa H, Ikeda S - Arch. Dermatol. Res. (2011)

The effects of YKS and fexofenadine on dermatitis score (a), TEWL (b), the numbers of scratching behaviors (c) and grooming behaviors (d) for AD-like skin lesions in NC/Nga mice. a The skin lesions of the conventional control group were aggravated as time goes on. Both the YKS- and the fexofenadine-treated groups significantly inhibited the aggravation of skin lesions in NC/Nga mice from 3 weeks after the start of the experiments. The dermatitis score of the SPF control group was not more than a minor increase. b The TEWL of the conventional control group was increased as time goes on. The YKS- and the fexofenadine-treated groups significantly inhibited the increase of TEWL compared with the conventional control mice from 3 weeks. The TEWL of the SPF group, which had no skin lesions, was not increased. c Scratching behaviors of the conventional control and the fexofenadine-treated groups increased as time goes on. The YKS-treated group significantly decreased the scratching behaviors compared with the conventional control group after 6 weeks. The scratching behaviors of the SPF group were not increased. d Grooming behaviors of the conventional control group and also the fexofenadine-treated group were increased under social isolated conditions. The YKS-treated group significantly decreased the grooming behaviors compared with the conventional control mice from 3 weeks. The grooming behaviors of the SPF group increased under social isolated conditions. SPF control: unfilled circle, conventional control: filled circle, YKS: filled square, fexofenadine: filled triangle. Data are presented as means ± SE (n = 5–6). †p < 0.05, ††p < 0.01 vsersu SPF control, *p < 0.05, **p < 0.01 versus conventional control, one-way ANOVA followed by Bonferroni/Dunn test
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Related In: Results  -  Collection

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Fig1: The effects of YKS and fexofenadine on dermatitis score (a), TEWL (b), the numbers of scratching behaviors (c) and grooming behaviors (d) for AD-like skin lesions in NC/Nga mice. a The skin lesions of the conventional control group were aggravated as time goes on. Both the YKS- and the fexofenadine-treated groups significantly inhibited the aggravation of skin lesions in NC/Nga mice from 3 weeks after the start of the experiments. The dermatitis score of the SPF control group was not more than a minor increase. b The TEWL of the conventional control group was increased as time goes on. The YKS- and the fexofenadine-treated groups significantly inhibited the increase of TEWL compared with the conventional control mice from 3 weeks. The TEWL of the SPF group, which had no skin lesions, was not increased. c Scratching behaviors of the conventional control and the fexofenadine-treated groups increased as time goes on. The YKS-treated group significantly decreased the scratching behaviors compared with the conventional control group after 6 weeks. The scratching behaviors of the SPF group were not increased. d Grooming behaviors of the conventional control group and also the fexofenadine-treated group were increased under social isolated conditions. The YKS-treated group significantly decreased the grooming behaviors compared with the conventional control mice from 3 weeks. The grooming behaviors of the SPF group increased under social isolated conditions. SPF control: unfilled circle, conventional control: filled circle, YKS: filled square, fexofenadine: filled triangle. Data are presented as means ± SE (n = 5–6). †p < 0.05, ††p < 0.01 vsersu SPF control, *p < 0.05, **p < 0.01 versus conventional control, one-way ANOVA followed by Bonferroni/Dunn test
Mentions: Dermatitis scores of the conventional control group were aggravated as time goes on. Both the YKS- and the fexofenadine-treated groups significantly inhibited the aggravation of skin lesions in NC/Nga mice from 3 weeks after the start of the experiments. The dermatitis score of the SPF control group was not more than a minor increase (Fig. 1a). The TEWL of the conventional control group was increased as time goes on. The YKS- and the fexofenadine-treated groups significantly inhibited the increase of TEWL compared with the conventional control mice from 3 weeks. The TEWL of the SPF group, which had no skin lesions, was not increased (Fig. 1b). Scratching behaviors of the conventional control and the fexofenadine-treated groups increased as time goes on. The YKS-treated group significantly decreased the scratching behaviors compared with the conventional control group after 6 weeks. The scratching behaviors of the SPF group was not increased (Fig. 1c). Grooming behaviors of the conventional control group and the fexofenadine-treated group were increased under social isolated conditions. The YKS-treated group significantly decreased the grooming behaviors compared to the conventional control mice from 3 weeks. The grooming behaviors of the SPF group increased under social isolated conditions (Fig. 1d).Fig. 1

Bottom Line: Yokukansan (YKS) has been used in Japan as a remedy for neurosis, insomnia, and children with night crying.YKS and fexofenadine inhibited the aggravation of skin lesions and decreased TEWL, but only YKS decreased the numbers of scratching and pathologic grooming behaviors.Furthermore, the effects of YKS are suggested to be mediated via glutamate signaling in the skin lesions.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, Juntendo University School of Medicine, Hongo, Bunkyo-ku, Tokyo, Japan. nao2794@juntendo.ac.jp

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.

Show MeSH
Related in: MedlinePlus