Rosmarinic Acid Attenuates Rotenone-Induced Neurotoxicity in SH-SY5Y Parkinson’s Disease Cell Model through Abl Inhibition

Abstract

Rosmarinic acid (RA) is a natural polyphenolic compound with antioxidative property. With the present study, we aimed to evaluate the neuroprotective role of RA on Parkinson’s disease using rotenone induced SH-SY5Y cell model of Parkinson’s disease, the underlying mechanism of action of RA was also investigated. Cell viability, cell morphology, apoptosis, signaling protein phosphorylation and expression, cellular reactive oxygen species (ROS) production, ATP content, and mitochondrial membrane potential were tested in SH-SY5Y cells. RA showed a neuroprotective effect in a rotenone-induced SH-SY5Y cell model of Parkinson’s disease with dose-dependent manner, it reduced cell apoptosis and restored normal cell morphology. RA not only decreased levels of α-synuclein and Tau phosphorylation but also elevated the contents of AMPK phosphorylation, Akt phosphorylation, and PGC-1α. RA restored the reduced mitochondrial membrane potential and ATP content as well as inhibited rotenone-induced ROS overproduction. Further findings demonstrated that the neuroprotective role of RA was partially due to the inhibition of Abl tyrosine kinase. RA treatment suppressed the hyperphosphorylation of Abl Y412 and CrkII Y221 induced by rotenone. Nilotinib, a specific inhibitor of Abl, elicited a similar neuroprotective effect as that of RA. The present study indicates that RA has a property of neuroprotection against rotenone, and the neuroprotective effect is partially attributed to the inhibition of Abl.