This study compared the antioxidant activity of various parts of Broussonetia papyrifera (BP), and further evaluated the protective effects of BP against hydrogen peroxide (H(2)O(2))-induced neuronal injury in human neuroblastoma SH-SY5Y cells. Among four BP parts, BP radix and leaf possessed the best scavenging activities for 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid (ABTS) radical, and H(2)O(2). These two BP parts also had higher phenolic and phenylpropanoid contents. Following exposure of cells to H(2)O(2), there was a marked decrease in cell survival, intracellular glutathione levels, and antioxidant enzymes, as well as an increase in intracellular oxidative stress. DNA fragmentation was also observed, but pretreatment of the cells with BP radix but not leaf prior to H(2)O(2) exposure blocked these H(2)O(2)-induced cellular events. The present findings indicate that BP radix exerts protective effects against H(2)O(2) toxicity via its free radical scavenging activity, which might be due to its total phenolic compounds.