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題名 Therapeutic effects of honokiol on motor impairment in hemiparkinsonian mice are associated with reversing neurodegeneration and targeting PPARr regulation
作者 Chen, Hwei-Hsien;Chang, Pei-Chi;Wey, Shiaw-Pyng;Chen, Pei-Mei;Chen, Chinpiao;Chan, Ming-Huan
詹銘煥
Chan, Ming-Huan
貢獻者 神科所
關鍵詞 6-Hydroxydopamine ; Honokiol ; PPARγ ; Parkinson’s disease ; Positron-emission tomography
日期 2018-12
上傳時間 13-Dec-2018 19:56:03 (UTC+8)
摘要 Parkinson`s disease (PD) is a profound neurodegenerative disorder with gradual loss of dopamine nigrostriatal neurons linked to serious behavioral symptoms. While the current treatment strategies present limitations on halting the progression of PD, this study aimed to investigate the therapeutic potential of honokiol, as a partial peroxisome proliferator-activated receptor-gamma (PPARγ) mimic, on the proceeding behavioral and biochemical alterations in hemiparkinsonian mice. Results showed that unilateral striatal 6-hydroxydopamine (6-OHDA)-lesioned mice exhibited motor impairment, reflecting the contralateral rotation induced by apomorphine at 1-3 weeks post-lesion. Subchronic honokiol administration for 1-2 weeks, beginning 7 days after 6-OHDA-lesion, dose-dependently ameliorated motor dysfunction in hemiparkinsonian mice. Recovery of motor function was correlated with reversal of nigrostriatal dopaminergic neuronal loss, accompanied by higher tyrosine hydroxylase (TH) density, dopamine transporter (DAT) expression and vesicular monoamine transporter-2 (VMAT2) levels. Furthermore, honokiol attenuated oxidative stress and reactive astrocyte induction via decreasing NADPH-oxidase and glial fibrillary acidic protein (GFAP) expressions in 6-OHDA-lesioned striatum. The reversal effects of honokiol on behavioral impairment and striatal PPARγ expression were impeded by PPARγ antagonist GW9662. Notably, subchronic honokiol treatment extended the lifespan of these hemiparkinsonian mice. The present findings demonstrate the therapeutic activities of honokiol in ameliorating motor impairment and progressive dopaminergic damage that could be associated with regulating PPARγ signaling. Therefore, honokiol may potentially exert as a novel therapeutic candidate through PPARγ activation for management of motor symptoms and progressive neurodegeneration in PD.
關聯 Biomedicine & Pharmacotherapy, Volume 108, Pages 254-262
資料類型 article
DOI http://dx.doi.org/10.1016/j.biopha.2018.07.095
dc.contributor 神科所
dc.creator (作者) Chen, Hwei-Hsien;Chang, Pei-Chi;Wey, Shiaw-Pyng;Chen, Pei-Mei;Chen, Chinpiao;Chan, Ming-Huanen_US
dc.creator (作者) 詹銘煥zh_TW
dc.creator (作者) Chan, Ming-Huanen_US
dc.date (日期) 2018-12
dc.date.accessioned 13-Dec-2018 19:56:03 (UTC+8)-
dc.date.available 13-Dec-2018 19:56:03 (UTC+8)-
dc.date.issued (上傳時間) 13-Dec-2018 19:56:03 (UTC+8)-
dc.identifier.uri (URI) http://nccur.lib.nccu.edu.tw/handle/140.119/121383-
dc.description.abstract (摘要) Parkinson`s disease (PD) is a profound neurodegenerative disorder with gradual loss of dopamine nigrostriatal neurons linked to serious behavioral symptoms. While the current treatment strategies present limitations on halting the progression of PD, this study aimed to investigate the therapeutic potential of honokiol, as a partial peroxisome proliferator-activated receptor-gamma (PPARγ) mimic, on the proceeding behavioral and biochemical alterations in hemiparkinsonian mice. Results showed that unilateral striatal 6-hydroxydopamine (6-OHDA)-lesioned mice exhibited motor impairment, reflecting the contralateral rotation induced by apomorphine at 1-3 weeks post-lesion. Subchronic honokiol administration for 1-2 weeks, beginning 7 days after 6-OHDA-lesion, dose-dependently ameliorated motor dysfunction in hemiparkinsonian mice. Recovery of motor function was correlated with reversal of nigrostriatal dopaminergic neuronal loss, accompanied by higher tyrosine hydroxylase (TH) density, dopamine transporter (DAT) expression and vesicular monoamine transporter-2 (VMAT2) levels. Furthermore, honokiol attenuated oxidative stress and reactive astrocyte induction via decreasing NADPH-oxidase and glial fibrillary acidic protein (GFAP) expressions in 6-OHDA-lesioned striatum. The reversal effects of honokiol on behavioral impairment and striatal PPARγ expression were impeded by PPARγ antagonist GW9662. Notably, subchronic honokiol treatment extended the lifespan of these hemiparkinsonian mice. The present findings demonstrate the therapeutic activities of honokiol in ameliorating motor impairment and progressive dopaminergic damage that could be associated with regulating PPARγ signaling. Therefore, honokiol may potentially exert as a novel therapeutic candidate through PPARγ activation for management of motor symptoms and progressive neurodegeneration in PD.en_US
dc.format.extent 3140934 bytes-
dc.format.mimetype application/pdf-
dc.relation (關聯) Biomedicine & Pharmacotherapy, Volume 108, Pages 254-262
dc.subject (關鍵詞) 6-Hydroxydopamine ; Honokiol ; PPARγ ; Parkinson’s disease ; Positron-emission tomography
dc.title (題名) Therapeutic effects of honokiol on motor impairment in hemiparkinsonian mice are associated with reversing neurodegeneration and targeting PPARr regulationen_US
dc.type (資料類型) article
dc.identifier.doi (DOI) 10.1016/j.biopha.2018.07.095
dc.doi.uri (DOI) http://dx.doi.org/10.1016/j.biopha.2018.07.095