Novel neuroprotective effects of oxyresveratrol preventing 6-hydroxydopamine-induced neurotoxicity: antioxidant activity and up-regulation of sirt1

Abstract

Oxyresveratrol (OXY) is a natural hydroxylated stilbene existing in mulberry. OXY is antioxidant, blood-brain-barrier permeable and readily water-soluble. Numerous reports have shown its neuroprotective effects against Alzheimer’s disease (AD) and stroke. As little is known about its neuroprotective effects on Parkinson’s disease (PD), we investigate whether OXY can prevent parkinsonian mimetic 6-hydroxydopamine (6-OHDA) neurotoxicity. In SH-SY5Y cells, both pretreatment and post-treatment with OXY significantly reduced lactate dehydrogenase release and caspase-3 activity. Moreover, OXY exhibited a wide effective window compared to resveratrol. Our experimental results have demonstrated that OXY could penetrate cell membrane by HPLC analysis of cell extract. In this notion, OXY may act as intracellular antioxidants to significantly repress the generation of reactive oxygen species (ROS) triggered by 6-OHDA. Therefore, OXY markedly attenuated 6-OHDA-induced phosphorylation of JNK and c-Jun. Apart from the conventional antioxidant activity, we proved that OXY up-regulated the expression of SirT1 repressed by 6-OHDA, and prevented the acetylation of downstream p53. Taken together, both antioxidant activity and up-regulation of SirT1 by OXY may be responsible for preventing 6-OHDA-induced neurotoxicity, and dietary OXY can be a potential candidate for nutritional supplement preventing neurodegeneration from PD.