Thymoquinone Prevents Dopaminergic Neurodegeneration by Attenuating Oxidative Stress Via the Nrf2/ARE Pathway
Studies have indicated that oxidative stress plays a crucial role in the development of Parkinson’s disease (PD) and other neurodegenerative conditions. Research has also revealed that nuclear factor erythroid 2-related factor 2 (Nrf2) triggers the expression of antioxidant genes via a series of ant...
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Frontiers Media S.A.
2021-01-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2020.615598/full |
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| author | Jianjian Dong Jianjian Dong Jianjian Dong Xiaoming Zhang Xiaoming Zhang Shijing Wang Chenchen Xu Manli Gao Manli Gao Songyang Liu Songyang Liu Xiaoxiao Li Xiaoxiao Li Nan Cheng Nan Cheng Yongsheng Han Yongsheng Han Xun Wang Xun Wang Yongzhu Han Yongzhu Han |
| author_facet | Jianjian Dong Jianjian Dong Jianjian Dong Xiaoming Zhang Xiaoming Zhang Shijing Wang Chenchen Xu Manli Gao Manli Gao Songyang Liu Songyang Liu Xiaoxiao Li Xiaoxiao Li Nan Cheng Nan Cheng Yongsheng Han Yongsheng Han Xun Wang Xun Wang Yongzhu Han Yongzhu Han |
| author_sort | Jianjian Dong |
| collection | DOAJ |
| description | Studies have indicated that oxidative stress plays a crucial role in the development of Parkinson’s disease (PD) and other neurodegenerative conditions. Research has also revealed that nuclear factor erythroid 2-related factor 2 (Nrf2) triggers the expression of antioxidant genes via a series of antioxidant response elements (AREs), thus preventing oxidative stress. Thymoquinone (TQ) is the bioactive component of Nigella sativa, a medicinal plant that exhibits antioxidant and neuroprotective effects. In the present study we examined whether TQ alleviates in vivo and in vitro neurodegeneration induced by 1-methyl-4-phenylpyridinium (MPP+) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) by acting as an activator of the Nrf2/ARE cascade. We showed that TQ significantly reduced MPP+-mediated cell death and apoptosis. Moreover, TQ significantly elevated the nuclear translocation of Nrf2 and significantly increased the subsequent expression of antioxidative genes such as Heme oxygenase 1 (HO-1), quinone oxidoreductase (NQO1) and Glutathione-S-Transferase (GST). The application of siRNA to silence Nrf2 led to an abolishment in the protective effects of TQ. We also found that the intraperitoneal injection of TQ into a rodent model of PD ameliorated oxidative stress and effectively mitigated nigrostriatal dopaminergic degeneration by activating the Nrf2-ARE pathway. However, these effects were inhibited by the injection of a lentivirus wrapped Nrf2 siRNA (siNrf2). Collectively, these findings suggest that TQ alleviates progressive dopaminergic neuropathology by activating the Nrf2/ARE signaling cascade and by attenuating oxidative stress, thus demonstrating that TQ is a potential novel drug candidate for the treatment of PD. |
| first_indexed | 2024-12-16T10:09:16Z |
| format | Article |
| id | doaj.art-0aeb41af0c9243cb8ec0e3d4983587f0 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-16T10:09:16Z |
| publishDate | 2021-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-0aeb41af0c9243cb8ec0e3d4983587f02022-12-21T22:35:36ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-01-011110.3389/fphar.2020.615598615598Thymoquinone Prevents Dopaminergic Neurodegeneration by Attenuating Oxidative Stress Via the Nrf2/ARE PathwayJianjian Dong0Jianjian Dong1Jianjian Dong2Xiaoming Zhang3Xiaoming Zhang4Shijing Wang5Chenchen Xu6Manli Gao7Manli Gao8Songyang Liu9Songyang Liu10Xiaoxiao Li11Xiaoxiao Li12Nan Cheng13Nan Cheng14Yongsheng Han15Yongsheng Han16Xun Wang17Xun Wang18Yongzhu Han19Yongzhu Han20High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, ChinaUniversity of Science and Technology of China, Hefei, ChinaThe Affiliated Hospital of the Neurology Institute, Anhui University of Chinese Medicine, Hefei, ChinaHigh Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, ChinaUniversity of Science and Technology of China, Hefei, ChinaThe Affiliated Hospital of the Neurology Institute, Anhui University of Chinese Medicine, Hefei, ChinaThe Affiliated Hospital of the Neurology Institute, Anhui University of Chinese Medicine, Hefei, ChinaThe Affiliated Hospital of the Neurology Institute, Anhui University of Chinese Medicine, Hefei, ChinaAnhui University of Chinese Medicine, Hefei, ChinaThe Affiliated Hospital of the Neurology Institute, Anhui University of Chinese Medicine, Hefei, ChinaAnhui University of Chinese Medicine, Hefei, ChinaThe Affiliated Hospital of the Neurology Institute, Anhui University of Chinese Medicine, Hefei, ChinaAnhui University of Chinese Medicine, Hefei, ChinaThe Affiliated Hospital of the Neurology Institute, Anhui University of Chinese Medicine, Hefei, ChinaAnhui University of Chinese Medicine, Hefei, ChinaThe Affiliated Hospital of the Neurology Institute, Anhui University of Chinese Medicine, Hefei, ChinaAnhui University of Chinese Medicine, Hefei, ChinaThe Affiliated Hospital of the Neurology Institute, Anhui University of Chinese Medicine, Hefei, ChinaAnhui University of Chinese Medicine, Hefei, ChinaThe Affiliated Hospital of the Neurology Institute, Anhui University of Chinese Medicine, Hefei, ChinaAnhui University of Chinese Medicine, Hefei, ChinaStudies have indicated that oxidative stress plays a crucial role in the development of Parkinson’s disease (PD) and other neurodegenerative conditions. Research has also revealed that nuclear factor erythroid 2-related factor 2 (Nrf2) triggers the expression of antioxidant genes via a series of antioxidant response elements (AREs), thus preventing oxidative stress. Thymoquinone (TQ) is the bioactive component of Nigella sativa, a medicinal plant that exhibits antioxidant and neuroprotective effects. In the present study we examined whether TQ alleviates in vivo and in vitro neurodegeneration induced by 1-methyl-4-phenylpyridinium (MPP+) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) by acting as an activator of the Nrf2/ARE cascade. We showed that TQ significantly reduced MPP+-mediated cell death and apoptosis. Moreover, TQ significantly elevated the nuclear translocation of Nrf2 and significantly increased the subsequent expression of antioxidative genes such as Heme oxygenase 1 (HO-1), quinone oxidoreductase (NQO1) and Glutathione-S-Transferase (GST). The application of siRNA to silence Nrf2 led to an abolishment in the protective effects of TQ. We also found that the intraperitoneal injection of TQ into a rodent model of PD ameliorated oxidative stress and effectively mitigated nigrostriatal dopaminergic degeneration by activating the Nrf2-ARE pathway. However, these effects were inhibited by the injection of a lentivirus wrapped Nrf2 siRNA (siNrf2). Collectively, these findings suggest that TQ alleviates progressive dopaminergic neuropathology by activating the Nrf2/ARE signaling cascade and by attenuating oxidative stress, thus demonstrating that TQ is a potential novel drug candidate for the treatment of PD.https://www.frontiersin.org/articles/10.3389/fphar.2020.615598/fullParkinson’ s diseasethymoquinoneNrf2/ARE signaling pathwayoxidative stressneurodegeneration |
| spellingShingle | Jianjian Dong Jianjian Dong Jianjian Dong Xiaoming Zhang Xiaoming Zhang Shijing Wang Chenchen Xu Manli Gao Manli Gao Songyang Liu Songyang Liu Xiaoxiao Li Xiaoxiao Li Nan Cheng Nan Cheng Yongsheng Han Yongsheng Han Xun Wang Xun Wang Yongzhu Han Yongzhu Han Thymoquinone Prevents Dopaminergic Neurodegeneration by Attenuating Oxidative Stress Via the Nrf2/ARE Pathway Frontiers in Pharmacology Parkinson’ s disease thymoquinone Nrf2/ARE signaling pathway oxidative stress neurodegeneration |
| title | Thymoquinone Prevents Dopaminergic Neurodegeneration by Attenuating Oxidative Stress Via the Nrf2/ARE Pathway |
| title_full | Thymoquinone Prevents Dopaminergic Neurodegeneration by Attenuating Oxidative Stress Via the Nrf2/ARE Pathway |
| title_fullStr | Thymoquinone Prevents Dopaminergic Neurodegeneration by Attenuating Oxidative Stress Via the Nrf2/ARE Pathway |
| title_full_unstemmed | Thymoquinone Prevents Dopaminergic Neurodegeneration by Attenuating Oxidative Stress Via the Nrf2/ARE Pathway |
| title_short | Thymoquinone Prevents Dopaminergic Neurodegeneration by Attenuating Oxidative Stress Via the Nrf2/ARE Pathway |
| title_sort | thymoquinone prevents dopaminergic neurodegeneration by attenuating oxidative stress via the nrf2 are pathway |
| topic | Parkinson’ s disease thymoquinone Nrf2/ARE signaling pathway oxidative stress neurodegeneration |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2020.615598/full |
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