Abstract
Given the role of oxidative stress in PD pathogenesis and off-target side effects of currently available drugs, several natural phytochemicals seems to be promising in the management of PD. Here, we tested the hypothesis that scopoletin, an active principle obtained from Morinda citrifolia (MC), efficiently quenches oxidative stress through DJ-1/Nrf2 signalling and ameliorates rotenone-induced PD. Despite reducing the oxidative stress, administration of MC extract (MCE) has lessened the protein aggregation as evident from decreased levels of nitrotyrosine and α-Synuclein. In vitro studies revealed that scopoletin lessened rotenone-induced apoptosis in SH-SY5Y cells through preventing oxidative injury. Particularly, scopoletin markedly up-regulated DJ-1, which then promoted the nuclear translocation of Nrf2 and transactivation of antioxidant genes. Furthermore, we found that scopoletin prevent the nuclear exportation of Nrf2 by reducing the levels of Keap1 and thereby enhancing the neuronal defence system. Overall, our findings suggest that scopoletin acts through DJ-1 mediated Nrf2 signalling to protect the brain from rotenone-induced oxidative stress and PD. Thus, we postulate that scopoletin could be a potential drug to treat PD.
Abbreviations
- DMSO
- Dimethyl Sulfoxide
- F-12K
- Kaighn's Modification of Ham's F-12 Medium
- FBS
- Fetal bovine serum
- GSH
- Reduced Glutathione
- HO-1
- Heme Oxygenase-1
- Keap1
- Kelch-like erythroid cell derived protein with CNC (Cap “n” Collar) homology (ECH) protein1
- LD
- Levodopa
- LPO
- Lipid peroxidation
- MCE
- Ethyl acetate extract of Morinda citrifolia fruit
- NO
- Nitric oxide
- NQO1
- NAD(P)H: Quinone Oxidoreductase 1
- Nrf2
- Nuclear factor erythroid 2-related factor 2
- PC
- Protein Carbonyl
- PD
- Parkinson’s disease
- PKC-δ
- Protein kinase C delta
- ROS
- Reactive oxygen species
- Rot Ind
- Rotenone induced
- SH-SY5Y
- neuroblast-like subclone of SK-N-SH
- SNpc
- Substantia nigra pars compacta
- VTA
- Ventral Tegmental Area
- γGCLC
- Catalytic subunit of Gamma Glutamate Cysteine Ligase