Neuroprotective Capability of Narcissoside in 6-OHDA-Exposed Parkinson’s Disease Models through Enhancing the MiR200a/Nrf-2/GSH Axis and Mediating MAPK/Akt Associated Signaling Pathway
We assessed the antioxidant potential of narcissoside from <i>Sambucus nigra</i> 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 a...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/11/2089 |
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| author | Ru-Huei Fu Chia-Wen Tsai Shih-Ping Liu Shao-Chih Chiu Yen-Chuan Chen Yu-Ting Chiang Yun-Hua Kuo Woei-Cherng Shyu Shinn-Zong Lin |
| author_facet | Ru-Huei Fu Chia-Wen Tsai Shih-Ping Liu Shao-Chih Chiu Yen-Chuan Chen Yu-Ting Chiang Yun-Hua Kuo Woei-Cherng Shyu Shinn-Zong Lin |
| author_sort | Ru-Huei Fu |
| collection | DOAJ |
| description | We assessed the antioxidant potential of narcissoside from <i>Sambucus nigra</i> 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 <i>Caenorhabditis elegans</i> 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 γ-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. |
| first_indexed | 2024-03-09T19:18:52Z |
| format | Article |
| id | doaj.art-3071b2834c84421b84da6aad452837c2 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T19:18:52Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-3071b2834c84421b84da6aad452837c22023-11-24T03:29:02ZengMDPI AGAntioxidants2076-39212022-10-011111208910.3390/antiox11112089Neuroprotective Capability of Narcissoside in 6-OHDA-Exposed Parkinson’s Disease Models through Enhancing the MiR200a/Nrf-2/GSH Axis and Mediating MAPK/Akt Associated Signaling PathwayRu-Huei Fu0Chia-Wen Tsai1Shih-Ping Liu2Shao-Chih Chiu3Yen-Chuan Chen4Yu-Ting Chiang5Yun-Hua Kuo6Woei-Cherng Shyu7Shinn-Zong Lin8Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, TaiwanDepartment of Nutrition, China Medical University, Taichung 40402, TaiwanGraduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, TaiwanGraduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, TaiwanGraduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, TaiwanGraduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, TaiwanGraduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, TaiwanGraduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, TaiwanBuddhist Tzu Chi Bioinnovation Center, Tzu Chi Foundation, Hualien 97002, TaiwanWe assessed the antioxidant potential of narcissoside from <i>Sambucus nigra</i> 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 <i>Caenorhabditis elegans</i> 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 γ-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.https://www.mdpi.com/2076-3921/11/11/2089Parkinson diseasenarcissoside6-hydroxydopamineSH-SY5Y<i>C. elegans</i>apoptosis |
| spellingShingle | Ru-Huei Fu Chia-Wen Tsai Shih-Ping Liu Shao-Chih Chiu Yen-Chuan Chen Yu-Ting Chiang Yun-Hua Kuo Woei-Cherng Shyu Shinn-Zong Lin Neuroprotective Capability of Narcissoside in 6-OHDA-Exposed Parkinson’s Disease Models through Enhancing the MiR200a/Nrf-2/GSH Axis and Mediating MAPK/Akt Associated Signaling Pathway Antioxidants Parkinson disease narcissoside 6-hydroxydopamine SH-SY5Y <i>C. elegans</i> apoptosis |
| title | Neuroprotective Capability of Narcissoside in 6-OHDA-Exposed Parkinson’s Disease Models through Enhancing the MiR200a/Nrf-2/GSH Axis and Mediating MAPK/Akt Associated Signaling Pathway |
| title_full | Neuroprotective Capability of Narcissoside in 6-OHDA-Exposed Parkinson’s Disease Models through Enhancing the MiR200a/Nrf-2/GSH Axis and Mediating MAPK/Akt Associated Signaling Pathway |
| title_fullStr | Neuroprotective Capability of Narcissoside in 6-OHDA-Exposed Parkinson’s Disease Models through Enhancing the MiR200a/Nrf-2/GSH Axis and Mediating MAPK/Akt Associated Signaling Pathway |
| title_full_unstemmed | Neuroprotective Capability of Narcissoside in 6-OHDA-Exposed Parkinson’s Disease Models through Enhancing the MiR200a/Nrf-2/GSH Axis and Mediating MAPK/Akt Associated Signaling Pathway |
| title_short | Neuroprotective Capability of Narcissoside in 6-OHDA-Exposed Parkinson’s Disease Models through Enhancing the MiR200a/Nrf-2/GSH Axis and Mediating MAPK/Akt Associated Signaling Pathway |
| title_sort | neuroprotective capability of narcissoside in 6 ohda exposed parkinson s disease models through enhancing the mir200a nrf 2 gsh axis and mediating mapk akt associated signaling pathway |
| topic | Parkinson disease narcissoside 6-hydroxydopamine SH-SY5Y <i>C. elegans</i> apoptosis |
| url | https://www.mdpi.com/2076-3921/11/11/2089 |
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