A novel compound derived from Zanthoxylum, gx-50(N-[2-(3, 4-dimethoxyphenyl)ethyl]-3-phenyl-acrylamide), has been demonstrated that it has neuroprotective effects against Alzheimer’s disease(AD)by our previous study.This study focuses on the mechanism of its antioxidant properties against AD.We measured the levels of intracellular reactive oxygen species(ROS), superoxide dismutase(SOD)activity and malondialdehyde(MDA)to determine the anti-oxidative ability of gx-50 at cellular level.We also measured gx-50’s effect on JAK-STAT signaling pathway and the relative expression levels of activated caspase-3.Data showed that gx-50 reduced the levels of reactive oxygen species(ROS)and malondialdehyde(MDA), and recovered the activity of total intracellular superoxide dismutase(SOD)in neuronal PC12 cells exposed to Aβ.After gx-50 pretreatment, the levels of p-JAK2 and p-STAT3 both increased in PC12 cells, while they were down-regulated in Aβ-treated group.In present study, we also found that gx-50 reduced the relative expression level of the activated caspase-3 in PC12 cells by activating JAK-STAT signaling pathway.Results demonstrated that gx-50 reduced amyloid-beta(Aβ)induced oxidative stress in neuron-like PC12 cells by enhancing the activation of JAK-STAT signaling pathway.It might help to protect neurons in Alzheimer's disease.