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Scope: We investigated the cytoprotective effects of cyanidin-3-O-glucoside (C3G) against oxidative stress and apoptosis induced by beta-amyloid 1-40 (Aβ 1-40 ) in SH-SY5Y cells. Methods and results We measured intracellular reactive oxygen species (ROS) with fluorescent marker DCFH2-DA, superoxide dismutase (SOD), hydrogen peroxide (H 2 O 2 ), glutathione peroxidase (GSH-Px) with the kits, and calcium, cellular apoptosis with Fluo-3/AM, annexin-V-FITC staining, respectively. C3G pretreatment significantly inhibited the Aβ 1-40 -induced increase in intracellular calcium, ROS, H 2 O 2 , increased the expression of SOD, GSH-Px and the antioxidant enzyme involved in the C3G’s antioxidant potential, including heme oxygenase-1 (HO-1), quinone oxidoreductase 1(NQO-1) regulated by nuclear factor erythroid 2-related factor-2 ( Nrf2 ). Western blotting, RT-PCR revealed that C3G significantly increased Nrf2 , HO-1 , NQO-1 expression. Besides, apoptosis was significantly inhibited by C3G via down-regulation of pro-apoptosis factor Bax and up-regulation of anti-apoptosis factor Bcl-2. Conclusion C3G protects SH-SY5Y cells from Aβ 1-40 -induced oxidative stress and subsequent apoptosis by regulating cellular antioxidant defenses and apoptosis-related genes. [ABSTRACT FROM AUTHOR]