Potent activity of nobiletin-rich Citrus reticulata peel extract to facilitate cAMP/PKA/ERK/CREB signaling associated with learning and memory in cultured hippocampal neurons: Identification of the substances responsible for the pharmacological action

Ichiro Kawahata, Masaaki Yoshida, Wen Sun, Akira Nakajima, Yanxin Lai, Naoya Osaka, Kentaro Matsuzaki, Akihito Yokosuka, Yoshihiro Mimaki, Akira Naganuma, Yoshihisa Tomioka, Tohru Yamakuni

研究成果: Article

38 引用 (Scopus)

抜粋

cAMP/PKA/ERK/CREB signaling linked to CRE-mediated transcription is crucial for learning and memory. We originally found nobiletin as a natural compound that stimulates this intracellular signaling and exhibits anti-dementia action in animals. Citrus reticulata or C.unshiu peels are employed as "chinpi" and include a small amount of nobiletin. We here provide the first evidence for beneficial pharmacological actions on the cAMP/PKA/ERK/CREB cascade of extracts from nobiletin-rich C.reticulata peels designated as Nchinpi, the nobiletin content of which was 0.83 ± 0.13 % of the dry weight or 16-fold higher than that of standard chinpi extracts. Nchinpi extracts potently facilitated CRE-mediated transcription in cultured hippocampal neurons, whereas the standard chinpi extracts showed no such activity. Also, the Nchinpi extract, but not the standard chinpi extract, stimulated PKA/ERK/CREB signaling. Interestingly, treatment with the Nchinpi extract at the concentration corresponding to approximately 5 μM nobiletin more potently facilitated CRE-mediated transcriptional activity than did 30 μM nobiletin alone. Consistently, sinensetin, tangeretin, 6-demethoxynobiletin, and 6-demethoxytangeretin were also identified as bioactive substances in Nchinpi that facilitated the CRE-mediated transcription. Purified sinensetin enhanced the transcription to a greater degree than nobiletin. Furthermore, samples reconstituted with the four purified compounds and nobiletin in the ratio of each constituent's content in the extract showed activity almost equal to that of the Nchinpi extract to stimulate CRE-mediated transcription. These findings suggest that above four compounds and nobiletin in the Nchinpi extract mainly cooperated to facilitate potently CRE-mediated transcription linked to the upstream cAMP/PKA/ERK/CREB pathway in hippocampal neurons.

元の言語English
ページ(範囲)1397-1409
ページ数13
ジャーナルJournal of Neural Transmission
120
発行部数10
DOI
出版物ステータスPublished - 2013 10

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry

フィンガープリント Potent activity of nobiletin-rich Citrus reticulata peel extract to facilitate cAMP/PKA/ERK/CREB signaling associated with learning and memory in cultured hippocampal neurons: Identification of the substances responsible for the pharmacological action' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

  • これを引用