Neuronal apoptosis induced by oxidative stress is a prominent feature of neurodegenerative disorders. -shogaol, a bio-active compound in ginger, possesses potent anti-inflammatory actions and has recently emerged as a potential therapeutic agent for neurodegenerative disorders. However, the effects of -shogaol on astroglial apoptosis following exogenously induced oxidative stress has not yet been investigated. Here, we show that the anti-apoptotic activity of -shogaol in astrocytes following exposure to hydrogen peroxide (H2O2) involves a marked up-regulation of neurotrophic factors such as nerve growth factor, glial cell line-derived neurotrophic factor, and brain-derived neurotrophic factor. Astrocytes co-treated with -shogaol and H2O2 for 1 h showed decrease in reactive oxygen species production compared with those only treated with H2O2. Moreover, -shogaol counteracted the reduced expression of ERK1/2 in H2O2-treated astrocytes and protected these cells from oxidative stress and apoptosis by attenuating the impairment of mitochondrial function proteins such as Bcl-2 and Bcl-xL. Additionally, -shogaol inhibits the expression of the apoptotic proteins Bax and caspase-3 in H2O2-treated astrocytes. This data suggest that following oxidative stress, -shogaol protects astrocytes from oxidative damage through the up-regulating levels of neurotrophic factors. These findings provide further support for the use of -shogaol as a therapeutic agent in neurodegenerative disorders. Copyright © 2013 John Wiley & Sons, Ltd.