1. Academic Validation
  2. Naturally occurring Ngn2 promoter activators from Butea superba

Naturally occurring Ngn2 promoter activators from Butea superba

  • Mol Biosyst. 2013 Oct;9(10):2489-97. doi: 10.1039/c3mb70083f.
Midori A Arai 1 Kazune Koryudzu Takashi Koyano Thaworn Kowithayakorn Masami Ishibashi
Affiliations

Affiliation

  • 1 Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan. midori_arai@chiba-u.jp.
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 mM compared with control. Of active natural compounds, 30-methoxydaidzein (3) showed promotion of neurite outgrowth of C17.2 in a secondary screen. 30-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.

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