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

In the present study, we aim to define the cytoprotective mechanism of (-)schisandrin B (-)Sch B. in comparison with other phytochemicals in SH-SY5Y cells. The effects of (-)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 (-)Sch B and EGCG protected against Aβ-induced apoptosis in SH-SY5Y cells. The cytoprotection afforded by (-)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 (-)Sch B, but not EGCG, increased G6DPH and GR activities in Aβ-challenged cells and caused the activation of Nrf2 in unchallenged cells. Both (-)Sch B and EGCG reduced the extent of Tau phosphorylayion in Aβ-challenged cells. In conclusion, (-)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 (-)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.