3 research outputs found
Inubosins A, B, and C Are Acridine Alkaloids Isolated from a Culture of <i>Streptomyces</i> sp. IFM 11440 with Ngn2 Promoter Activity
Three new acridine alkaloids, inubosins
A (<b>1</b>), B (<b>2</b>), and C (<b>3</b>), were
isolated from an extract
of a culture of <i>Streptomyces</i> sp. IFM 11440 using
bioassay-guided fractionation. Neurogenin2 (Ngn2) is an activator-type
basic helix–loop–helix transcription factor that promotes
neural stem cell differentiation. Using cell-based Ngn2 promoter activity-guided
screening, <i>Streptomyces</i> sp. IFM 11440 was found to
induce Ngn2 promoter activity. The structures of <b>1</b>–<b>3</b> were established using spectroscopic methods, including
1D- and 2D-NMR measurements. Inubosin B (<b>2</b>) showed potent
Ngn2 promoter activity. Moreover, inubosin B (<b>2</b>) increased
mRNA expression of genes related to neural stem cell differentiation
Notch Inhibitors from <i>Calotropis gigantea</i> That Induce Neuronal Differentiation of Neural Stem Cells
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 <i>Calotropis
gigantea</i> were identified as inhibitors of the Notch signaling
pathway. <i>Hes1</i> and <i>Hes5</i> are target
genes of the Notch signaling pathway, and compound <b>1</b>,
called uscharin, decreased the protein levels of Hes1 and Hes5 in
assay cells and MEB5 cells (mouse NSCs). Furthermore, uscharin (<b>1</b>) enhanced the differentiation of MEB5 cells into neurons.
The mechanism of uscharin (<b>1</b>) for the Notch signaling
inhibitory activity would be acceleration of the degradation of the
Notch intracellular domain (NICD) in the MEB5 cells