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A Flavonoid-Rich Extract of Mandarin Juice Counteracts 6-OHDA-Induced Oxidative Stress in SH-SY5Y Cells and Modulates Parkinson-Related Genes
Parkinson’s disease (PD) is a degenerative disorder of the nervous system due to unceasing impairment of dopaminergic neurons situated in the substantia nigra. At present, anti-PD drugs acting on dopamine receptors are mainly symptomatic and have only very limited neuroprotective effects, whereas dr...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066648/ https://www.ncbi.nlm.nih.gov/pubmed/33808343 http://dx.doi.org/10.3390/antiox10040539 |
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author | Cirmi, Santa Maugeri, Alessandro Lombardo, Giovanni Enrico Russo, Caterina Musumeci, Laura Gangemi, Sebastiano Calapai, Gioacchino Barreca, Davide Navarra, Michele |
author_facet | Cirmi, Santa Maugeri, Alessandro Lombardo, Giovanni Enrico Russo, Caterina Musumeci, Laura Gangemi, Sebastiano Calapai, Gioacchino Barreca, Davide Navarra, Michele |
author_sort | Cirmi, Santa |
collection | PubMed |
description | Parkinson’s disease (PD) is a degenerative disorder of the nervous system due to unceasing impairment of dopaminergic neurons situated in the substantia nigra. At present, anti-PD drugs acting on dopamine receptors are mainly symptomatic and have only very limited neuroprotective effects, whereas drugs slowing down neurodegeneration of dopaminergic neurons and deterioration of clinical symptoms are not yet available. Given that, the development of more valuable pharmacological strategies is highly demanded. Comprehensive research on innovative neuroprotective drugs has proven that anti-inflammatory and antioxidant molecules from food sources may prevent and/or counteract neurodegenerative diseases, such as PD. The present study was aimed at the evaluation the protective effect of mandarin juice extract (MJe) against 6-hydroxydopamine (6-OHDA)-induced SH-SY5Y human neuroblastoma cell death. Treatment of differentiated SH-SY5Y cells with 6-OHDA brought cell death, and specifically, apoptosis, which was significantly inhibited by the preincubation with MJe through caspase 3 blockage and the modulation of p53, Bax, and Bcl-2 genes. In addition, it showed antioxidant properties in abiotic models as well as in vitro, where it reduced both reactive oxygen and nitrogen species induced by 6-OHDA, along with restored mitochondrial membrane potential, and prevented the oxidative DNA damage evoked by 6-OHDA. Furthermore, MJe restored the impaired balance of SNCA, LRRK2, PINK1, parkin, and DJ-1 gene levels, PD-related factors, caused by 6-OHDA oxidative stress. Overall, these results indicate that MJe exerts neuroprotective effects against 6-OHDA-induced cell death in SH-SY5Y cells by mechanisms involving both the specific interaction with intracellular pathways and its antioxidant capability. Our study suggests a novel possible strategy to prevent and/or ameliorate neurodegenerative diseases, such as PD. |
format | Online Article Text |
id | pubmed-8066648 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-80666482021-04-25 A Flavonoid-Rich Extract of Mandarin Juice Counteracts 6-OHDA-Induced Oxidative Stress in SH-SY5Y Cells and Modulates Parkinson-Related Genes Cirmi, Santa Maugeri, Alessandro Lombardo, Giovanni Enrico Russo, Caterina Musumeci, Laura Gangemi, Sebastiano Calapai, Gioacchino Barreca, Davide Navarra, Michele Antioxidants (Basel) Article Parkinson’s disease (PD) is a degenerative disorder of the nervous system due to unceasing impairment of dopaminergic neurons situated in the substantia nigra. At present, anti-PD drugs acting on dopamine receptors are mainly symptomatic and have only very limited neuroprotective effects, whereas drugs slowing down neurodegeneration of dopaminergic neurons and deterioration of clinical symptoms are not yet available. Given that, the development of more valuable pharmacological strategies is highly demanded. Comprehensive research on innovative neuroprotective drugs has proven that anti-inflammatory and antioxidant molecules from food sources may prevent and/or counteract neurodegenerative diseases, such as PD. The present study was aimed at the evaluation the protective effect of mandarin juice extract (MJe) against 6-hydroxydopamine (6-OHDA)-induced SH-SY5Y human neuroblastoma cell death. Treatment of differentiated SH-SY5Y cells with 6-OHDA brought cell death, and specifically, apoptosis, which was significantly inhibited by the preincubation with MJe through caspase 3 blockage and the modulation of p53, Bax, and Bcl-2 genes. In addition, it showed antioxidant properties in abiotic models as well as in vitro, where it reduced both reactive oxygen and nitrogen species induced by 6-OHDA, along with restored mitochondrial membrane potential, and prevented the oxidative DNA damage evoked by 6-OHDA. Furthermore, MJe restored the impaired balance of SNCA, LRRK2, PINK1, parkin, and DJ-1 gene levels, PD-related factors, caused by 6-OHDA oxidative stress. Overall, these results indicate that MJe exerts neuroprotective effects against 6-OHDA-induced cell death in SH-SY5Y cells by mechanisms involving both the specific interaction with intracellular pathways and its antioxidant capability. Our study suggests a novel possible strategy to prevent and/or ameliorate neurodegenerative diseases, such as PD. MDPI 2021-03-30 /pmc/articles/PMC8066648/ /pubmed/33808343 http://dx.doi.org/10.3390/antiox10040539 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Cirmi, Santa Maugeri, Alessandro Lombardo, Giovanni Enrico Russo, Caterina Musumeci, Laura Gangemi, Sebastiano Calapai, Gioacchino Barreca, Davide Navarra, Michele A Flavonoid-Rich Extract of Mandarin Juice Counteracts 6-OHDA-Induced Oxidative Stress in SH-SY5Y Cells and Modulates Parkinson-Related Genes |
title | A Flavonoid-Rich Extract of Mandarin Juice Counteracts 6-OHDA-Induced Oxidative Stress in SH-SY5Y Cells and Modulates Parkinson-Related Genes |
title_full | A Flavonoid-Rich Extract of Mandarin Juice Counteracts 6-OHDA-Induced Oxidative Stress in SH-SY5Y Cells and Modulates Parkinson-Related Genes |
title_fullStr | A Flavonoid-Rich Extract of Mandarin Juice Counteracts 6-OHDA-Induced Oxidative Stress in SH-SY5Y Cells and Modulates Parkinson-Related Genes |
title_full_unstemmed | A Flavonoid-Rich Extract of Mandarin Juice Counteracts 6-OHDA-Induced Oxidative Stress in SH-SY5Y Cells and Modulates Parkinson-Related Genes |
title_short | A Flavonoid-Rich Extract of Mandarin Juice Counteracts 6-OHDA-Induced Oxidative Stress in SH-SY5Y Cells and Modulates Parkinson-Related Genes |
title_sort | flavonoid-rich extract of mandarin juice counteracts 6-ohda-induced oxidative stress in sh-sy5y cells and modulates parkinson-related genes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066648/ https://www.ncbi.nlm.nih.gov/pubmed/33808343 http://dx.doi.org/10.3390/antiox10040539 |
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