Dl-3-n-Butylphthalide Exerts Dopaminergic Neuroprotection Through Inhibition of Neuroinflammation
Microglia-mediated neuroinflammation contributes to multiple neurodegenerative disorders, including PD. Therefore, the regulation of microglial activation probably has the therapeutic potential. This study is aimed to determine whether NBP could suppress microglial activation and protect dopaminergi...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-02-01
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| Series: | Frontiers in Aging Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fnagi.2019.00044/full |
| _version_ | 1828382743053991936 |
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| author | Yajing Chen Tingting Wu Heng Li Xuan Li Qing Li Xiaoying Zhu Mei Yu Sheng-Han Kuo Fang Huang Yun-Cheng Wu |
| author_facet | Yajing Chen Tingting Wu Heng Li Xuan Li Qing Li Xiaoying Zhu Mei Yu Sheng-Han Kuo Fang Huang Yun-Cheng Wu |
| author_sort | Yajing Chen |
| collection | DOAJ |
| description | Microglia-mediated neuroinflammation contributes to multiple neurodegenerative disorders, including PD. Therefore, the regulation of microglial activation probably has the therapeutic potential. This study is aimed to determine whether NBP could suppress microglial activation and protect dopaminergic neurons from excessive neuroinflammation. In the present study, MPTP-induced PD model was established to explore the neuroprotective and anti-inflammatory effect of NBP. We assessed motor deficits, dopaminergic neurodegeneration and microglial activation in PD mice. In vitro, the anti-inflammatory activity of NBP was confirmed by cell viability assay of SH-SY5Y cells after being treated with conditioned medium from LPS-stimulated BV-2 cells and from 1-Methyl-4-phenylpyridinium iodide (MPP+)-stimulated BV-2 cells. The expression of pro-inflammatory molecules was determined by RT-PCR, Western Blot and ELISA assay. The generation of NO and ROS were also assessed. The involvement of signaling pathways such as MAPK, NF-κB, and PI3k/Akt were further investigated by Western Blot and immunofluorescence assay. The neuroprotective effect of NBP was demonstrated in vivo as shown by the improvement of dopaminergic neurodegeneration, motor deficits and microglial activation in MPTP-induced mouse model of PD. The expression of pro-inflammatory mediators was also reduced by NBP administration. In vitro, NBP also protected dopaminergic neurons from neurotoxicity induced by activated microglia. NBP pretreatment not only reduced pro-inflammatory molecules, but also suppressed NO release and ROS generation in BV-2 cells. Further mechanism research suggested that the inactivation of MAPK, NF-κB and PI3K/Akt may involve in anti-neuroinflammation role of NBP. In conclusion, our results revealed that NBP exerted dopaminergic neuroprotection through inhibition of microglia-mediated neuroinflammation, suggesting the promising therapeutic effect of NBP for PD. |
| first_indexed | 2024-12-10T04:37:48Z |
| format | Article |
| id | doaj.art-be106bf92bb34b22a0a337bea535a23e |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-10T04:37:48Z |
| publishDate | 2019-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-be106bf92bb34b22a0a337bea535a23e2022-12-22T02:01:58ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652019-02-011110.3389/fnagi.2019.00044440804Dl-3-n-Butylphthalide Exerts Dopaminergic Neuroprotection Through Inhibition of NeuroinflammationYajing Chen0Tingting Wu1Heng Li2Xuan Li3Qing Li4Xiaoying Zhu5Mei Yu6Sheng-Han Kuo7Fang Huang8Yun-Cheng Wu9Department of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Neurology, Jinan Central Hospital Affiliated to Shandong University, Jinan, ChinaDepartment of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaThe State Key Laboratory of Medical Neurobiology, The Institutes of Brain Science and the Collaborative Innovation Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaThe State Key Laboratory of Medical Neurobiology, The Institutes of Brain Science and the Collaborative Innovation Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, United StatesThe State Key Laboratory of Medical Neurobiology, The Institutes of Brain Science and the Collaborative Innovation Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaMicroglia-mediated neuroinflammation contributes to multiple neurodegenerative disorders, including PD. Therefore, the regulation of microglial activation probably has the therapeutic potential. This study is aimed to determine whether NBP could suppress microglial activation and protect dopaminergic neurons from excessive neuroinflammation. In the present study, MPTP-induced PD model was established to explore the neuroprotective and anti-inflammatory effect of NBP. We assessed motor deficits, dopaminergic neurodegeneration and microglial activation in PD mice. In vitro, the anti-inflammatory activity of NBP was confirmed by cell viability assay of SH-SY5Y cells after being treated with conditioned medium from LPS-stimulated BV-2 cells and from 1-Methyl-4-phenylpyridinium iodide (MPP+)-stimulated BV-2 cells. The expression of pro-inflammatory molecules was determined by RT-PCR, Western Blot and ELISA assay. The generation of NO and ROS were also assessed. The involvement of signaling pathways such as MAPK, NF-κB, and PI3k/Akt were further investigated by Western Blot and immunofluorescence assay. The neuroprotective effect of NBP was demonstrated in vivo as shown by the improvement of dopaminergic neurodegeneration, motor deficits and microglial activation in MPTP-induced mouse model of PD. The expression of pro-inflammatory mediators was also reduced by NBP administration. In vitro, NBP also protected dopaminergic neurons from neurotoxicity induced by activated microglia. NBP pretreatment not only reduced pro-inflammatory molecules, but also suppressed NO release and ROS generation in BV-2 cells. Further mechanism research suggested that the inactivation of MAPK, NF-κB and PI3K/Akt may involve in anti-neuroinflammation role of NBP. In conclusion, our results revealed that NBP exerted dopaminergic neuroprotection through inhibition of microglia-mediated neuroinflammation, suggesting the promising therapeutic effect of NBP for PD.https://www.frontiersin.org/article/10.3389/fnagi.2019.00044/fulldl-3-n-butylphthalideMAPKmicroglianeuroinflammationNF-κBParkinson’s disease |
| spellingShingle | Yajing Chen Tingting Wu Heng Li Xuan Li Qing Li Xiaoying Zhu Mei Yu Sheng-Han Kuo Fang Huang Yun-Cheng Wu Dl-3-n-Butylphthalide Exerts Dopaminergic Neuroprotection Through Inhibition of Neuroinflammation Frontiers in Aging Neuroscience dl-3-n-butylphthalide MAPK microglia neuroinflammation NF-κB Parkinson’s disease |
| title | Dl-3-n-Butylphthalide Exerts Dopaminergic Neuroprotection Through Inhibition of Neuroinflammation |
| title_full | Dl-3-n-Butylphthalide Exerts Dopaminergic Neuroprotection Through Inhibition of Neuroinflammation |
| title_fullStr | Dl-3-n-Butylphthalide Exerts Dopaminergic Neuroprotection Through Inhibition of Neuroinflammation |
| title_full_unstemmed | Dl-3-n-Butylphthalide Exerts Dopaminergic Neuroprotection Through Inhibition of Neuroinflammation |
| title_short | Dl-3-n-Butylphthalide Exerts Dopaminergic Neuroprotection Through Inhibition of Neuroinflammation |
| title_sort | dl 3 n butylphthalide exerts dopaminergic neuroprotection through inhibition of neuroinflammation |
| topic | dl-3-n-butylphthalide MAPK microglia neuroinflammation NF-κB Parkinson’s disease |
| url | https://www.frontiersin.org/article/10.3389/fnagi.2019.00044/full |
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