Quercetin enhanced proliferation of neural stem/ progenitor cells through Nrf2-proteasome pathway

Introduction: Quercetin, a natural flavonoid, has been suggested as a stimulant of endogenous neural stem cell proliferation; but, its underlying mechanism is unclear. Considering that Nrf2 and proteasome pathways have important role in cell proliferation, the objective of this study was to evaluate the effects of different concentrations of quercetin on Nrf2 protein levels and proteasomal activity in neural stem/progenitor cells (NS/PCs) in relation to NS/PCs viability and proliferation. Methods: NS/PCs of rat fetal ganglionic eminence were cultured and exposed to different concentrations of quercetin (1, 5 and 15μM) or DMSO for 7 days. The size and number of neurospheres and percentage of BrdU positive cells were measured as indexes of cell proliferation. MTT assay was used for evaluating the cell viability. Proteasomal activity and Nrf2 protein levels were determined using proteasomal activity kit and western immunoblotting, respectively. Results: Quercetin increased the percentage of BrdU positive cells, size and number of neurospheres and viability of NS/PCs and increased Nrf2 protein levels and 20S proteasome activity in comparison to DMSO. The effects of quercetin on NS/PCs proliferation, Nrf2 levels and proteasome activity were concentration-dependent. Conclusion: The results of this study indicated that quercetin increased Nrf2 levels and proteasome activity in parallel to enhanced NS/PCs proliferation in a concentration-dependent manner. These findings suggest that quercetin may exert its stimulatory effect on NS/PCs proliferation through the enhancement of Nrf2- proteasome pathway. Quercetin as activators of Nrf2 and proteasome can be suggested as a potential treatment for neurodegenerative conditions to promote endogenous cell proliferation.