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