Comparison of Neurogenesis Promotion Effects between Cinnamoylquinic Acids in Neural Stem Cells from Adult Mice Brains

Caffeoylquinic acids (CQAs) and feruloylquinic acids (FQAs), as cinnamoylquinic acids, have neurogenesis promotion effects. We studied for the first time the neurogenesis-enhancing effect of 3,4,5-tri-feruloylquinic acid (TFQA) compared to 3,4,5-tri-caffeoylquinic acid (TCQA), which has a similar structure, and explored their different cellular and molecular mechanisms in neural stem cells (NSCs) of mice brains. After 2 weeks of incubation, we first assessed the number and size of NSCs in TCQA and TFQA treatments. In NSCs treated for TCQA and TFQA, the NSC proliferation gene expression as well as neuronal and glial cell differentiation gene expressions improved. In the microarray assay, the erythroblastic oncogene B (ErbB) signaling pathway, as the common signaling of TCQA and TFQA treatments, was focused on and discussed. In our study, TCQA and TFQA treatments in NSCs showed a significant performance on improving synapse growth and neurogenesis compared with no treatment of NSCs. The two treatments in NSCs also had a significant activation of the ErbB signaling pathway, protein kinase B (AKT), and mitogen-activated protein kinase (MAPK) kinases. In particular, the TCQA-expressed proliferation gene myelocytomatosis oncogene (Myc) had the greatest connections significantly. TFQA treatment remarkably regulated the differentiation gene jun proto-oncogene (Jun), which was the gene with greatest direct relations, while Myc was also induced in TFQA treatment. In the overall quantitative real-time polymerase chain reaction (PCR) assay, TFQA had more outstanding neural proliferation and differentiation capabilities than TCQA in NSCs. Our study suggests that TFQA has greater therapeutic potential in neurogenesis promotion and neurodegenerative diseases compared with TCQA.