Polydatin Prevents Lipopolysaccharide (LPS)-Induced Parkinson's Disease via Regulation of the AKT/GSK3β-Nrf2/NF-κB Signaling Axis
Parkinson's disease (PD) is a common neurodegenerative disease characterized by selective loss of dopaminergic neurons in the substantia nigra (SN). Neuroinflammation induced by over-activation of microglia leads to the death of dopaminergic neurons in the pathogenesis of PD. Therefore, downreg...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.02527/full |
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| author | Bingxu Huang Juxiong Liu Tianyu Meng Yuhang Li Dewei He Xin Ran Guangxin Chen Guangxin Chen Wenjin Guo Xingchi Kan Shoupeng Fu Wei Wang Dianfeng Liu |
| author_facet | Bingxu Huang Juxiong Liu Tianyu Meng Yuhang Li Dewei He Xin Ran Guangxin Chen Guangxin Chen Wenjin Guo Xingchi Kan Shoupeng Fu Wei Wang Dianfeng Liu |
| author_sort | Bingxu Huang |
| collection | DOAJ |
| description | Parkinson's disease (PD) is a common neurodegenerative disease characterized by selective loss of dopaminergic neurons in the substantia nigra (SN). Neuroinflammation induced by over-activation of microglia leads to the death of dopaminergic neurons in the pathogenesis of PD. Therefore, downregulation of microglial activation may aid in the treatment of PD. Polydatin (PLD) has been reported to pass through the blood-brain barrier and protect against motor degeneration in the SN. However, the molecular mechanisms underlying the effects of PLD in the treatment of PD remain unclear. The present study aimed to determine whether PLD protects against dopaminergic neurodegeneration by inhibiting the activation of microglia in a rat model of lipopolysaccharide (LPS)-induced PD. Our findings indicated that PLD treatment protected dopaminergic neurons and ameliorated motor dysfunction by inhibiting microglial activation and the release of pro-inflammatory mediators. Furthermore, PLD treatment significantly increased levels of p-AKT, p-GSK-3βSer9, and Nrf2, and suppressed the activation of NF-κB in the SN of rats with LPS-induced PD. To further explore the neuroprotective mechanism of PLD, we investigated the effect of PLD on activated microglial BV-2 cells. Our findings indicated that PLD inhibited the production of pro-inflammatory mediators and the activation of NF-κB pathways in LPS-induced BV-2 cells. Moreover, our results indicated that PLD enhanced levels of p-AKT, p-GSK-3βSer9, and Nrf2 in BV-2 cells. After BV-2 cells were pretreated with MK2206 (an inhibitor of AKT), NP-12 (an inhibitor of GSK-3β), or Brusatol (BT; an inhibitor of Nrf2), treatment with PLD suppressed the activation of NF-κB signaling pathways and the release of pro-inflammatory mediators in activated BV-2 cells via activation of the AKT/GSK3β-Nrf2 signaling axis. Taken together, our results are the first to demonstrate that PLD prevents dopaminergic neurodegeneration due to microglial activation via regulation of the AKT/GSK3β-Nrf2/NF-κB signaling axis. |
| first_indexed | 2024-12-11T18:20:34Z |
| format | Article |
| id | doaj.art-6f354044fd194e1ead75d16ab27ce3f2 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T18:20:34Z |
| publishDate | 2018-11-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-6f354044fd194e1ead75d16ab27ce3f22022-12-22T00:55:16ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-11-01910.3389/fimmu.2018.02527418533Polydatin Prevents Lipopolysaccharide (LPS)-Induced Parkinson's Disease via Regulation of the AKT/GSK3β-Nrf2/NF-κB Signaling AxisBingxu Huang0Juxiong Liu1Tianyu Meng2Yuhang Li3Dewei He4Xin Ran5Guangxin Chen6Guangxin Chen7Wenjin Guo8Xingchi Kan9Shoupeng Fu10Wei Wang11Dianfeng Liu12Department of Basic Veterinary Medicine, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, ChinaDepartment of Basic Veterinary Medicine, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, ChinaDepartment of Food Quality and Safety, College of Food Science and Engineering, Jilin University, Changchun, ChinaDepartment of Basic Veterinary Medicine, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, ChinaDepartment of Basic Veterinary Medicine, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, ChinaDepartment of Basic Veterinary Medicine, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, ChinaDepartment of Basic Veterinary Medicine, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, ChinaDepartment of Infection and Immunology, Institutes of Biomedical Sciences, Shanxi University, Taiyuan, ChinaDepartment of Basic Veterinary Medicine, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, ChinaDepartment of Basic Veterinary Medicine, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, ChinaDepartment of Basic Veterinary Medicine, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, ChinaDepartment of Basic Veterinary Medicine, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, ChinaDepartment of Basic Veterinary Medicine, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, ChinaParkinson's disease (PD) is a common neurodegenerative disease characterized by selective loss of dopaminergic neurons in the substantia nigra (SN). Neuroinflammation induced by over-activation of microglia leads to the death of dopaminergic neurons in the pathogenesis of PD. Therefore, downregulation of microglial activation may aid in the treatment of PD. Polydatin (PLD) has been reported to pass through the blood-brain barrier and protect against motor degeneration in the SN. However, the molecular mechanisms underlying the effects of PLD in the treatment of PD remain unclear. The present study aimed to determine whether PLD protects against dopaminergic neurodegeneration by inhibiting the activation of microglia in a rat model of lipopolysaccharide (LPS)-induced PD. Our findings indicated that PLD treatment protected dopaminergic neurons and ameliorated motor dysfunction by inhibiting microglial activation and the release of pro-inflammatory mediators. Furthermore, PLD treatment significantly increased levels of p-AKT, p-GSK-3βSer9, and Nrf2, and suppressed the activation of NF-κB in the SN of rats with LPS-induced PD. To further explore the neuroprotective mechanism of PLD, we investigated the effect of PLD on activated microglial BV-2 cells. Our findings indicated that PLD inhibited the production of pro-inflammatory mediators and the activation of NF-κB pathways in LPS-induced BV-2 cells. Moreover, our results indicated that PLD enhanced levels of p-AKT, p-GSK-3βSer9, and Nrf2 in BV-2 cells. After BV-2 cells were pretreated with MK2206 (an inhibitor of AKT), NP-12 (an inhibitor of GSK-3β), or Brusatol (BT; an inhibitor of Nrf2), treatment with PLD suppressed the activation of NF-κB signaling pathways and the release of pro-inflammatory mediators in activated BV-2 cells via activation of the AKT/GSK3β-Nrf2 signaling axis. Taken together, our results are the first to demonstrate that PLD prevents dopaminergic neurodegeneration due to microglial activation via regulation of the AKT/GSK3β-Nrf2/NF-κB signaling axis.https://www.frontiersin.org/article/10.3389/fimmu.2018.02527/fullparkinson's diseaseneuroinflammationpolydatinmicroglianeuroprotection |
| spellingShingle | Bingxu Huang Juxiong Liu Tianyu Meng Yuhang Li Dewei He Xin Ran Guangxin Chen Guangxin Chen Wenjin Guo Xingchi Kan Shoupeng Fu Wei Wang Dianfeng Liu Polydatin Prevents Lipopolysaccharide (LPS)-Induced Parkinson's Disease via Regulation of the AKT/GSK3β-Nrf2/NF-κB Signaling Axis Frontiers in Immunology parkinson's disease neuroinflammation polydatin microglia neuroprotection |
| title | Polydatin Prevents Lipopolysaccharide (LPS)-Induced Parkinson's Disease via Regulation of the AKT/GSK3β-Nrf2/NF-κB Signaling Axis |
| title_full | Polydatin Prevents Lipopolysaccharide (LPS)-Induced Parkinson's Disease via Regulation of the AKT/GSK3β-Nrf2/NF-κB Signaling Axis |
| title_fullStr | Polydatin Prevents Lipopolysaccharide (LPS)-Induced Parkinson's Disease via Regulation of the AKT/GSK3β-Nrf2/NF-κB Signaling Axis |
| title_full_unstemmed | Polydatin Prevents Lipopolysaccharide (LPS)-Induced Parkinson's Disease via Regulation of the AKT/GSK3β-Nrf2/NF-κB Signaling Axis |
| title_short | Polydatin Prevents Lipopolysaccharide (LPS)-Induced Parkinson's Disease via Regulation of the AKT/GSK3β-Nrf2/NF-κB Signaling Axis |
| title_sort | polydatin prevents lipopolysaccharide lps induced parkinson s disease via regulation of the akt gsk3β nrf2 nf κb signaling axis |
| topic | parkinson's disease neuroinflammation polydatin microglia neuroprotection |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.02527/full |
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