Treatment with quercetin increases Nrf2 expression and neuronal differentiation of sub ventricular zone derived neural progenitor stem cells in adult rats.

Abstract

Abstract Background The presence of neural precursor stem cells in some parts of the adult brain has been proven in recent years, and it has opened up a new approach for the treatment and recovery of the defects and diseases associated with the central nervous system. Besides, the potency of these types of cells with a therapeutic viewpoint is another beneficial facet of the application of neural progenitor stem cells (NPSCs) in cell biology. Quercetin, as an herbal flavonoid, has been extensively investigated and shown to have numerous restoratives, inhibitory, and protective effects on some cell-lines and disorders. Objective The purpose of this study is to simultaneously investigate the effect of quercetin on the expression of the nuclear factor erythroid 2–related factor 2 (Nrf2) gene and the effect on the proliferation and differentiation of neural progenitor stem cells derived from the subventricular zone (SVZ) of the brain of adult rats. Methods The brains of adult rats were dissected, and the two SVZs of the brain of each animal were removed. After crushing and extracting the cells the obtained cell suspension was cultured for one week to achieve neurospheres. Cells obtained from this step was treated with quercetin at the concentrations of 1, 5, and 15 µM to evaluate the impact of this substance on Nrf2 gene expression level, the proliferation and differentiation of NSCs after one week. Gene expression level and cell identification was performed by RT- PCR, survival test with MTT assay, quantification of images with Image-J and cells were counted. Results The results indicated that the quercetin increases expression of Nrf2 at concentration above 5 µM. Also differentiation and proliferation rate of NSCs is affected by various concentrations of quercetin in a dose-dependent manner so that 1µM quercetin had the least, and 15 µM quercetin showed the most effects on cell differentiation. However, 1 µM quercetin exhibited no significant cell toxicity, but the most antiproliferative potential showed when treated with 15 µM concentration quercetin. Conclusion These findings confirm previous information on the dose-dependent effect of quercetin on proliferation and differentiation of cell. In addition, quercetin increased the expression of Nrf2 gene. By combining these two effects of quercetin, this substance can be considered an effective compound in the treatment of degenerative defects such as Multiple Sclerosis, Alzheimer’s disease and Parkinson’s disease.