國家衛生研究院 NHRI:Item 3990099045/11429
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    题名: Therapeutic effects of honokiol on motor impairment in hemiparkinsonian mice are associated with reversing neurodegeneration and targeting PPARgamma regulation
    其它题名: Therapeutic effects of honokiol on motor impairment in hemiparkinsonian mice are associated with reversing neurodegeneration and targeting PPARγ regulation
    作者: Chen, HH;Chang, PC;Wey, SP;Chen, PM;Chen, C;Chan, MH
    贡献者: Center for Neuropsychiatric Research
    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.
    日期: 2018-12
    關聯: Biomedicine and Pharmacotherapy. 2018 Dec;108:254-262.
    Link to: http://dx.doi.org/10.1016/j.biopha.2018.07.095
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0753-3322&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000450101800031
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85053213414
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