Schisandrin B Enhances Glutathione Redox Cycling and Protects Against β-amyloid-induced Apoptosis in Human Neuroblastoma SH-SY5Y Cells: A Comparative Study of Various Phytochemicals

ABSTRACT

In the present study, we aim to define the cytoprotective mechanism of (β)schisandrin B [(β)Sch B] in comparison with other phytochemicals in SH-SY5Y cells. The effects of (β)Sch B and curcumin (Cur), resveratrol (Rev) and epigallocatechin gallate (EGCG) on b-amyloid (Ab)-induced apoptosis were investigated in SH-SY5Y cells. Cellular reduced glutathione (GSH) levels and peroxide-induced GSH depletion were measured. Activities of glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6DPH) in Aβ-challenged cells were also examined. All tested phytochemicals were investigated for the activation of nuclear factor erythroid-2 related factor 2 (Nrf2) in SH-SY5Y cells, using a luciferase-based assay. Finally, they were examined for the effect on the extent of phosphorylation of Tau in Ab- challenged cells. The results showed that only (β)Sch B and EGCG protected against Aβ-induced apoptosis in SH-SY5Y cells. The cytoprotection afforded by (β)Sch B and EGCG were associated with an increase in cellular GSH levels in Aβ- challenged cells and a reduction in peroxide-induced GSH depletion. However, only (β)Sch B, but not EGCG, increased G6DPH and GR activities in Aβ-challenged cells and caused the activation of Nrf2 in unchallenged cells. Both (β)Sch B and EGCG reduced the extent of Tau phosphorylayion in Aβ-challenged cells. In conclusion, (β)Sch B may enhance cellular glutathione redox cycling, presumably by increasing G6PDH and GR activities, via activation of the Nrf2 signaling pathway, whereas EGCG likely acts as a radical scavenger. Both (β)Sch B and EGCG suppressed the phosphorylation of Tau in Aβ-challenged cells, suggesting their potential in ameliorating the pathological condition of Alzheimer’s disease.

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