Neuroprotective effects of methylated resveratrols in an in vitro Parkinson’s disease model

Abstract

Emerging lines of evidence have supported the beneficial effects of methylated resveratrol derivatives on cardiovascular systems. However, little is known about the effects of its derivatives on the development of Parkinson’s disease (PD). In this study, the neuroprotective effects of resveratrol and four methylated resveratrol derivatives against parkinsonian mimetic 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in SH-SY5Y cells were compared. Lactate dehydrogenase release and caspase-3 activity triggered by 6-OHDA were significantly reduced by resveratrol and one of the methylated derivatives, pinostilbene (3,4’-dihydroxy-5-methoxystilbene) in a dose-dependent manner, exerting potent neuroprotective effects with a wider effective concentration range than resveratrol. In addition, high performance liquid chromatography showed significantly higher uptake of pinostilbene into SH-SY5Y cells than that of resveratrol. The enhanced bioavailability may thus be a major factor contributing to the neuroprotective activity of pinostilbene. Moreover, Western-blot analysis demonstrated that pinostilbene markedly attenuated the phosphorylation of JNK and c-Jun triggered by 6-OHDA. Mammalian target of rapamycin kinase may also be an intracellular target responsible for the neuroprotective effects of pinostilbene. Our findings demonstrate the potential of methylated stilbenes in neuroprotection and provide important information for further research in this field.