Notch Inhibitors from Calotropis gigantea That Induce Neuronal Differentiation of Neural Stem Cells

Tatsuro Yoneyama, Midori A. Arai, Ryuta Akamine, Kazune Koryudzu, Anna Tsuchiya, Samir K. Sadhu, Firoj Ahmed, Motoyuki Itoh, Ryuichi Okamoto, Masami Ishibashi

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease occur due to loss of the structure and function of neurons. For the potential treatment of neurodegenerative diseases, accelerators of neuronal differentiation of neural stem cells (NSCs) have been focused on and a cell-based assay system for measuring Notch signaling pathway activity was constructed. Using this assay system, eight compounds isolated from Calotropis gigantea were identified as inhibitors of the Notch signaling pathway. Hes1 and Hes5 are target genes of the Notch signaling pathway, and compound 1, called uscharin, decreased the protein levels of Hes1 and Hes5 in assay cells and MEB5 cells (mouse NSCs). Furthermore, uscharin (1) enhanced the differentiation of MEB5 cells into neurons. The mechanism of uscharin (1) for the Notch signaling inhibitory activity would be acceleration of the degradation of the Notch intracellular domain (NICD) in the MEB5 cells.

Original languageEnglish
Pages (from-to)2453-2461
Number of pages9
JournalJournal of Natural Products
Volume80
Issue number9
DOIs
Publication statusPublished - 2017 Jan 1
Externally publishedYes

ASJC Scopus subject areas

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

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    Yoneyama, T., Arai, M. A., Akamine, R., Koryudzu, K., Tsuchiya, A., Sadhu, S. K., Ahmed, F., Itoh, M., Okamoto, R., & Ishibashi, M. (2017). Notch Inhibitors from Calotropis gigantea That Induce Neuronal Differentiation of Neural Stem Cells. Journal of Natural Products, 80(9), 2453-2461. https://doi.org/10.1021/acs.jnatprod.7b00282