Thymoquinone Prevents Dopaminergic Neurodegeneration by Attenuating Oxidative Stress Via the Nrf2/ARE Pathway
文献类型：期刊论文
| 作者 | Dong, Jianjian1,2,3; Zhang, Xiaoming1,2; Wang, Shijing3; Xu, Chenchen3; Gao, Manli3,4; Liu, Songyang3,4; Li, Xiaoxiao3,4 ; Cheng, Nan3,4; Han, Yongsheng3,4; Wang, Xun3,4
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| 刊名 | FRONTIERS IN PHARMACOLOGY
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| 出版日期 | 2021-01-14 |
| 卷号 | 11 |
| 关键词 | Parkinson's disease thymoquinone Nrf2/ARE signaling pathway oxidative stress neurodegeneration |
| ISSN号 | 1663-9812 |
| DOI | 10.3389/fphar.2020.615598 |
| 通讯作者 | Wang, Xun(neurodoc@163.com) ; Han, Yongzhu(yonhzhuhan@163.com) |
| 英文摘要 | 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. |
| WOS关键词 | PARKINSONS-DISEASE ; NIGELLA-SATIVA ; CELL-DEATH ; ANTIOXIDANTS ; PATHOGENESIS ; MODEL |
| 资助项目 | National Natural Science Foundation of China[81603596] ; National Natural Science Foundation of China[81673948] ; National Natural Science Foundation of China[81774425] ; Natural Science Foundation of Anhui University of Chinese Medicine[2020sjzd03] ; University Natural Science Research Project of Anhui Province[KJ2019A0431] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000612212700001 |
| 出版者 | FRONTIERS MEDIA SA |
| 资助机构 | National Natural Science Foundation of China ; Natural Science Foundation of Anhui University of Chinese Medicine ; University Natural Science Research Project of Anhui Province |
| 源URL | [http://ir.hfcas.ac.cn:8080/handle/334002/119775]  |
| 专题 | 中国科学院合肥物质科学研究院 |
| 通讯作者 | Wang, Xun; Han, Yongzhu |
| 作者单位 | 1.Chinese Acad Sci, Hefei Inst Phys Sci, High Field Magnet Lab, Hefei, Peoples R China 2.Univ Sci & Technol China, Hefei, Peoples R China 3.Anhui Univ Chinese Med, Neurol Inst, Affiliated Hosp, Hefei, Peoples R China 4.Anhui Univ Chinese Med, Hefei, Peoples R China |
| 推荐引用方式 GB/T 7714 | Dong, Jianjian,Zhang, Xiaoming,Wang, Shijing,et al. Thymoquinone Prevents Dopaminergic Neurodegeneration by Attenuating Oxidative Stress Via the Nrf2/ARE Pathway[J]. FRONTIERS IN PHARMACOLOGY,2021,11. |
| APA | Dong, Jianjian.,Zhang, Xiaoming.,Wang, Shijing.,Xu, Chenchen.,Gao, Manli.,...&Han, Yongzhu.(2021).Thymoquinone Prevents Dopaminergic Neurodegeneration by Attenuating Oxidative Stress Via the Nrf2/ARE Pathway.FRONTIERS IN PHARMACOLOGY,11. |
| MLA | Dong, Jianjian,et al."Thymoquinone Prevents Dopaminergic Neurodegeneration by Attenuating Oxidative Stress Via the Nrf2/ARE Pathway".FRONTIERS IN PHARMACOLOGY 11(2021). |
入库方式： OAI收割
来源：合肥物质科学研究院
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