We previously reported that Smilacis chinae rhizome inhibits amyloid beta protein (25-35) (Abeta (25-35))-induced neurotoxicity in cultured rat cortical neurons. The present study evaluated the neuroprotective effect of oxyresveratrol isolated from Smilacis chinae rhizome against Abeta (25-35)-induced neurotoxicity on cultured rat cortical neurons. Oxyresveratrol over the concentration range of 1-10 microM significantly inhibited 10 microM Abeta (25-35)-induced neuronal cell death, which was measured by a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and Hoechst 33342 staining. Oxyresveratrol (10 microM) inhibited 10 microM Abeta (25-35)-induced elevation of cytosolic calcium concentration ([Ca2+]c), which was measured by a fluorescent dye, Fluo-4 AM. Oxyresveratrol (1, 10 microM) also inhibited glutamate release into medium and reactive oxygen species (ROS) generation induced by 10 microM Abeta (25-35). These results suggest that oxyresveratrol prevents Abeta (25-35)-induced neuronal cell damage by interfering with the increase of [Ca2+]c, and then by inhibiting glutamate release and ROS generation. Furthermore, these effects of oxyresveratrol may be associated with the neuroprotective effect of Smilacis chinae rhizome.