Acta Pharmacologica Sinica 2008 February; 29 (2): 152-160; doi: 10.1111/j.1745-7254.2008.00714.x

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 Aβ_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 Aβ_25-35 (25 µmol/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 µmol/L) markedly increased cell viability and decreased LDH release and morphological injury. Also, FLZ attenuated the Aβ_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 Aβ_25-35 in SH-SY5Y cells.

Conclusion: FLZ has protective action against Aβ_25-35-induced toxicity in SH-SY5Y cells, which might be mediated through its antioxidant property.

Keywords: compound FLZ; β-amyloid peptide; apoptosis; oxidative stress; SH-SY5Y cells