Oxyresveratrol (OXY) is a polyhydroxylated stilbene existing in mulberry. Increasing lines of evidence have
shown its neuroprotective effects against Alzheimer disease and stroke. However, little is known about its
neuroprotective effect in Parkinson disease (PD). Owing to its antioxidant activity, blood-brain barrier
permeativity, and water solubility, we hypothesized that OXY may exert neuroprotective effects against
parkinsonian mimetic 6-hydroxydopamine (6-OHDA) neurotoxicity. Neuroblastoma SH-SY5Y cells have
long been used as dopaminergic neurons in PD research. We found that both pretreatment and
posttreatment with OXY on SH-SY5Y cells significantly reduced the release of lactate dehydrogenase, the
activity of caspase-3, and the generation of intracellular reactive oxygen species triggered by 6-OHDA.
Compared to resveratrol, OXY exhibited a wider effective dosage range. We proved that OXY could
penetrate the cell membrane by HPLC analysis of cell extracts. These results suggest that OXY may act as
an intracellular antioxidant to reduce oxidative stress induced by 6-OHDA. Western blot analysis
demonstrated that OXY markedly attenuated 6-OHDA-induced phosphorylation of JNK and c-Jun.
Furthermore, we proved that OXY increased the basal levels of SIRT1, which may disclose new pathways
accounting for the neuroprotective effects of OXY. Taken together, our results suggest OXY, a dietary
phenolic compound, as a potential nutritional candidate for protection against neurodegeneration in PD.