176. 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.

Leong PK, Lam PY, Chen N, Ko KM

Division of Life Science, Hong Kong University of Science and Technology, Clear water bay, Hong Kong.

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.