Naturally occurring Ngn2 promoter activators from Butea superba

Midori A. Arai, Kazune Koryudzu, Takashi Koyano, Thaworn Kowithayakorn, Masami Ishibashi

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Neurogenin2 (Ngn2), an activator-type bHLH transcriptional factor, promotes differentiation of neural stem cells into neurons by transcription of pro-neural genes. To find neural stem cell accelerators from the extract library of natural resources, we used a two-step screening including a Ngn2 promoter reporter gene screening and differentiation assay screening of neural stem cells. A reporter gene assay that can detect Ngn2 promoter activity by luciferase expression was constructed using C3H10T1/2 cells. Using this primary cell-based screening, Butea superba was found to include Ngn2 promoter activators from our tropical plant extract libraries. Bioassay-guided fractionation of this plant extract led to the isolation of 18 natural products, including pterocarpans and isoflavonoids. Dehydromaackiain (1), formononetin (6), (-)-variabilin (13), (-)-medicarpin (14), rothindin (17) and ononin (18) showed 1.8-2.8 times higher Ngn2 promoter activity at 5 μM compared with control. Of active natural compounds, 3′-methoxydaidzein (3) showed promotion of neurite outgrowth of C17.2 in a secondary screen. 3′-Methoxydaidzein (3) increased mRNA expression of pro-neural transcriptional factors (Ngn2, Ngn1, NeuroD2), a mature neuron-specific enzyme GAD1 and a pro-neural neurotrophic growth factor neurotrophin 3 (NT3) in C17.2 neural stem cells.

Original languageEnglish
Pages (from-to)2489-2497
Number of pages9
JournalMolecular BioSystems
Volume9
Issue number10
DOIs
Publication statusPublished - 2013 Oct
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Biology

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