Regulatory effects of costunolide on dopamine metabolism-associated genes inhibit dopamine-induced apoptosis in human dopaminergic SH-SY5Y cells

摘要

Parkinson's disease (PD) is characterized by the selective loss of dopaminergic (DAergic) neurons in the substantia nigra and the subsequent depletion of dopamine (DA). This study assessed the protective effects of costunolide on DA-induced apoptosis in human DAergic SH-SY5Y cells, and its regulation of DA metabolism-associated gene and protein expression. Annexin V and propidium iodide (PI) staining using flow cytometric analysis (FACS) revealed that costunolide significantly protected human DAergic SH-SY5Y cells against DA-induced apoptosis. In addition, co-treatment of costunolide with DA in SH-SY5Y cells regulated DA metabolism-associated gene expression, as we observed an increase in both mRNA and protein levels of nuclear receptor related-1 (Nurr1), DA transporter (DAT), and vesicular monoamine transporter type 2 (VMAT2). In contrast, α-synuclein (ASYN) protein levels were decreased. Our findings suggest that costunolide has anti-apoptotic activity, presumably due to its regulatory effects on DA metabolism-associated genes. Therefore, costunolide could be considered as a candidate therapy for the treatment of Parkinson's disease.