Schisandrin B Enhances Glutathione Redox Cycling and Protects Againstβ-amyloid-induced Apoptosis in Human Neuroblastoma SH-SY5Y Cells: AComparative Study of Various Phytochemicals

摘要

In the present study, we aim to define the cytoprotective mechanism of (β)schisandrin B [(β)Sch B] incomparison 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. Cellularreduced glutathione (GSH) levels and peroxide-induced GSH depletion were measured. Activities of glutathionereductase (GR) and glucose-6-phosphate dehydrogenase (G6DPH) in Aβ-challenged cells were also examined. All testedphytochemicals 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-SY5Ycells. 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, increasedG6DPH and GR activities in Aβ-challenged cells and caused the activation of Nrf2 in unchallenged cells. Both (β)Sch Band EGCG reduced the extent of Tau phosphorylayion in Aβ-challenged cells. In conclusion, (β)Sch B may enhancecellular glutathione redox cycling, presumably by increasing G6PDH and GR activities, via activation of the Nrf2signaling pathway, whereas EGCG likely acts as a radical scavenger. Both (β)Sch B and EGCG suppressed thephosphorylation of Tau in Aβ-challenged cells, suggesting their potential in ameliorating the pathological condition ofAlzheimer’s disease.