Novel squamosamide derivative (compound FLZ) attenuates Aβ25-35-induced toxicity in SH-SY5Y cells

Aim: The aim of the present study was to investigate the protective effect of compound N-[2-(4-hydroxy-phenyl)-ethyl]-2-(2,5-dimethoxy-phenyl)-3-(3-methoxy-4-hydroxy-phenyl)-acrylamide (compound FLZ), a novel synthetic analogue of nature squamosamide, on A beta(25-35)-induced toxicity and its active mechanism in human neuroblastoma SH-SY5Y cells. Methods: SH-SY5Y cells were pre-incubated with various concentrations of compound FLZ for 30 min and then cultivated with A beta(25-35) (25 mu mol/L) for 48 h to induce neurotoxicity. Cell viability, lactate dehydrogenase (LDH) release, and the glutathione (GSH) level were determined by a biochemical analysis. The cell apoptotic ratio and intracellular reactive oxygen species (ROS) level were measured by a flow cytometry analysis. The expression of apoptosis protein (Bcl-2 and Bax) and cytochrome c release were assayed by the Western blot method. Results: The pretreatment of SH-SY5Y cells with FLZ (1 and 10 mu mol/L) markedly increased cell viability and decreased LDH release and morphological injury. Also, FLZ attenuated the A beta(25-35)-induced apoptotic cell ratio, regulated the apoptosis protein (Bcl-2 and Bax) expression, and decreased the cytochrome c release from mitochondria. FLZ also significantly inhibited the generation of ROS and the depletion of GSH induced by A beta(25-35) in SH-SY5Y cells. Conclusion: FLZ has protective action against A beta(25-35)-in-duced toxicity in SH-SY5Y cells, which might be mediated through its antioxidant property.