Abstract
Motoric disturbances in Parkinson’s disease (PD) derive from the loss of dopaminergic neurons in the substantia nigra. Intestinal dysfunctions often appear long before manifestation of neuronal symptoms, suggesting a strong correlation between gut and brain in PD. Oxidative stress is a key player in neurodegeneration causing neuronal cell death. Using natural antioxidative flavonoids like Rutin, might provide intervening strategies to improve PD pathogenesis. To explore the potential effects of micro (mRutin) compared to nano Rutin (nRutin) upon the brain and the gut during PD, its neuroprotective effects were assessed using an in vitro PD model. Our results demonstrated that Rutin inhibited the neurotoxicity induced by A53T α-synuclein (Syn) administration by decreasing oxidized lipids and increasing cell viability in both, mesencephalic and enteric cells. For enteric cells, neurite outgrowth, number of synaptic vesicles, and tyrosine hydroxylase positive cells were significantly reduced when treated with Syn. This could be reversed by the addition of Rutin. nRutin revealed a more pronounced result in all experiments. In conclusion, our study shows that Rutin, especially the nanocrystals, are promising natural compounds to protect neurons from cell death and oxidative stress during PD. Early intake of Rutin may provide a realizable option to prevent or slow PD pathogenesis.
Funding source: Bundesministerium für Bildung und Forschung
Award Identifier / Grant number: 03FH019I3
Acknowledgments
The transfected SH-SY5Y-A53T and the SH-SY5Y-WT cells were a kind gift of Dr. T. Hasegawa provided by Dr. M. Britschgi at Roche. LUHMES cell line was kindly provided by Prof. Marcel Leist (University of Konstanz; Germany).
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Author contributions: Anne Christmann and Manuela Gries, designed and supervised the experiments, analyzed and interpreted results, and wrote the manuscript. Patrik Scholz produced the Rutin nanocrystals and helped with their characterization. Jessica Ka Yan Law and Sven Ingebrandt performed DPPH Assay and helped with SH-SY5Y cell culture. Sven Ingebrandt supervised Jessica Ka Yan Law. Steven Schulte helped to generate and analyze the immunohistochemical data and assisted with the ENS sample preparations. Monika Martin performed the Western blot and assisted with LUHMES cell culture and ELISA. Rainer Lilischkis generated the SEM images from Rutin nanocrystals and ENS cells. Cornelia M. Keck developed the Rutin nanocrystals, oversaw the pharmaceutical part of the study, and supervised Patrik Scholz. Karl-Herbert Schäfer conceived the project, was responsible for the overall experimental design, was involved in data analysis, interpretation and discussion, and the final manuscript. All authors discussed the results and commented on the manuscript.
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Research funding: None declared.
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Conflict of interest statement: The authors declare that they have no conflicts of interest with the contents of this article.
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