Vol 59, No 1 (2021)
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Published online: 2021-02-18

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Genistein exerts a cell-protective effect via Nrf2/HO-1/ /PI3K signaling in Ab25-35-induced Alzheimer’s disease models in vitro

Shanqing Yi1, Shuangxi Chen1, Jian Xiang2, Jian Tan1, Kailiang Huang1, Hao Zhang3, Yilin Wang13, Heng Wu1
Pubmed: 33605427
Folia Histochem Cytobiol 2021;59(1):49-56.


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 Ab25–35via 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 neurodegenerative diseases related to Nrf2/HO-1/PI3K signaling.

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