期刊
ANTIOXIDANTS
卷 11, 期 11, 页码 -出版社
MDPI
DOI: 10.3390/antiox11112089
关键词
Parkinson disease; narcissoside; 6-hydroxydopamine; SH-SY5Y; C; elegans; apoptosis; glutathione; Nrf2; MAPK; miR200a
资金
- Ministry of Science and Technology (Taiwan) [MOST 110-2314-B-039-040-]
- China Medical University Hospital (Taiwan) [DMR-110-132]
We investigated the antioxidant potential of narcissoside in Parkinson's disease models and found that narcissoside can enhance the miR200a/Nrf2/GSH antioxidant pathway, reduce reactive oxygen species generation, and improve dopamine-related behavior. Moreover, narcissoside can activate the ERK and Akt pathways to resist apoptosis. These findings suggest that narcissoside has neuroprotective potential in Parkinson's disease.
We assessed the antioxidant potential of narcissoside from Sambucus nigra flowers (elderflowers) in Parkinson's disease models in vitro and in vivo. The results showed that narcissoside lessened the 6-hydroxydopamine (6-OHDA)-induced increase in reactive oxygen species (ROS) and apoptosis in SH-SY5Y cells. In the 6-OHDA-exposed Caenorhabditis elegans model, narcissoside reduced degeneration of dopaminergic neurons and ROS generation, and also improved dopamine-related food-sensitive behavior and shortened lifespan. Moreover, NCS increased total glutathione (GSH) by increasing the expression of the catalytic subunit and modifier subunit of gamma-glutamylcysteine ligase in cells and nematodes. Treatment with a GSH inhibitor partially abolished the anti-apoptotic ability of narcissoside. Furthermore, narcissoside diminished the 6-OHDA-induced phosphorylation of JNK and p38, while rising activities of ERK and Akt in resisting apoptosis. The antioxidant response element (ARE)-luciferase reporter activity analysis and electromobility gel shift assay showed that narcissoside promotes the transcriptional activity mediated by Nrf2. Finally, we found that narcissoside augmented the expression of miR200a, a translational inhibitor of the Nrf2 repressor protein Keap1. Downregulation of Nrf2 and miR200a by RNAi and anti-miR200a, respectively, reversed the neuroprotective ability of narcissoside. In summary, narcissoside can enhance the miR200a/Nrf2/GSH antioxidant pathway, alleviate 6-OHDA-induced apoptosis, and has the neuroprotective potential.
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