学術雑誌論文 CRF receptor 1 antagonism and brain distribution of active components contribute to the ameliorative effect of rikkunshito on stress-induced anorexia

Mogami, Sachiko  ,  Sadakane, Chiharu  ,  Nahata, Miwa  ,  Mizuhara, Yasuharu  ,  Yamada, Chihiro  ,  Hattori, Tomohisa  ,  Takeda, Hiroshi

6p.27516 , 2016-06-08 , Nature Publishing Group
ISSN:2045-2322
内容記述
Rikkunshito (RKT), a Kampo medicine, has been reported to show an ameliorative effect on sustained hypophagia after novelty stress exposure in aged mice through serotonin 2C receptor (5-HT2CR) antagonism. We aimed to determine (1) whether the activation of anorexigenic neurons, corticotropin-releasing factor (CRF), and pro-opiomelanocortin (POMC) neurons, is involved in the initiation of hypophagia induced by novelty stress in aged mice; (2) whether the ameliorative effect of RKT is associated with CRF and POMC neurons and downstream signal transduction; and (3) the plasma and brain distribution of the active components of RKT. The administration of RKT or 5-HT2CR, CRF receptor 1 (CRFR1), and melanocortin-4 receptor antagonists significantly restored the decreased food intake observed in aged male C57BL/6 mice in the early stage after novelty stress exposure. Seven components of RKT exhibited antagonistic activity against CRFR1. Hesperetin and isoliquiritigenin, which showed antagonistic effects against both CRFR1 and 5-HT2CR, were distributed in the plasma and brain of male Sprague-Dawley rats after a single oral administration of RKT. In conclusion, the ameliorative effect of RKT in this model is assumed to be at least partly due to brain-distributed active components possessing 5-HT2CR and CRFR1 antagonistic activities.
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http://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/62483/2/suppl.pdf

http://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/62483/1/manuscript.pdf

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