Quinic acid contributes to neurogenesis: Targeting Notch pathway a key player in hippocampus

Abstract

Coordinated proliferation and differentiation of neural stem cells (NSCs) results in continuous neurogenesis. The present study provides novel insights into the Notch intracellular signaling in neuronal cell proliferation, maintenance, migration, and differentiation regulated by naturally based Quinic acid (QA) in primary hippocampal cell culture. Further, this study might help in the discovery and development of lead molecules that can overcome the challenges in the treatment of neurodegenerative diseases. The growth supporting effect of QA was studied using Alamar Blue assay. The migratory potential of QA was evaluated using scratch assay. The in vitro H₂O₂-induced oxidative stress model was used to upregulate neuronal survival after QA treatment. The RT-qPCR and immunocytochemical analysis were performed for selected markers of Notch signaling to determine the proliferation, differentiation, and maintenance of NSCs at gene and molecular levels. The Mash1 and Ngn2 are the upstream proneural genes of the Notch pathway which were included to evaluate the differentiation of NSCs into mature neurons after treatment with QA.

Furthermore, regarding the role of QA in maintaining the pool of NPCs, we used Notch1 and Hes1 markers for proliferation analysis. Also, secondary neuronal markers i.e. Pax6, PCNA, and Mcm2 were included in this study and their gene expression analysis was analyzed following treatment with QA. Based on the study’s results, we suggest that naturally based QA can promote the growth and differentiation of neonatal NSCs residing in hippocampal regions into neuronal lineage. Therefore, we propose that the neurogenic potential of QA can be employed to prevent and treat neurodegenerative diseases.