Genistein exerts a cell-protective effect via nrf2/ho-1/ /pi3k signaling in ab25-35-induced alzheimer’s disease models in vitro

Abstract

Introduction. Alzheimer’s disease (AD), a very common neurodegenerative disorder, is mainly characterized by the deposition of b-amyloid protein (Ab) and extensive neuronal cell death. Currently, there are no satisfactory therapeutic approaches for AD. Although neuroprotective effects of genistein against Ab-induced toxicity have been reported, the underlying molecular mechanisms remain unclear. Furthermore, the PI3K/Akt/Nrf2 signaling pathway is associated with AD. The aim of the study was to investigate whether genistein can modulate Nrf2/HO-1/PI3K signaling to treat AD. Materials and methods. Cell viability assay, the measurement of heme oxygenase-1 (HO-1) expression by reverse transcription-polymerase chain reaction (RT-qPCR), and western blot were performed on the SH-SY5Y cells induced by Ab25–35 in response to the treatment with genistein. Moreover, PI3K p85 phosphorylation was measured. Results. Genistein enhanced the HO-1expression at both the mRNA and protein levels, as well as the PI3K p85 phosphorylation level. In addition, genistein increased the survival of SH-SY5Y cells treated with Ab25–35 via HO-1 signaling. However, following transfection with Nrf2 small interfering RNA (siRNA) and treatment with LY294002, an inhibitor of PI3K p85, genistein could not upregulate HO-1 to exert neuroprotective effects on SH-SY5Y cells treated with Ab25–35 . Conclusions. These results suggest that genistein exerts a neuroprotective effect on SH-SY5Y cells in vitro via Nrf2/ HO-1/PI3K signaling, providing a foundation for the application of genistein in the treatment of neurodegenera-tive diseases related to Nrf2/HO-1/PI3K signaling. (Folia Histochemica et Cytobiologica 2021, Vol. 59, No. 1, 49–56).