Hwei-Hsien Chen1, Pei-Chi Chang2, Chinpiao Chen3, Ming-Huan Chan4. 1. Center for Neuropsychiatric Research, National Health of Research Institutes, Miaoli, Taiwan; Institute of Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan. 2. Institute of Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan. 3. Department of Chemistry, National Dong Hwa University, Hualien, Taiwan. 4. Institute of Neuroscience, Research Center for Mind, Brain and Learning, National Chengchi University, Taipei, Taiwan. Electronic address: minghuan@nccu.edu.tw.
Abstract
BACKGROUND: Parkinson's disease (PD) is a progressive and profound movement disorder resulting from neurodegeneration in the nigrostriatal dopaminergic system, but current treatment neither cures nor stops PD from advancing. Based on the ability to suppress oxidative stress, excitotoxicity, and neuroinflammation, the potential of honokiol as a novel neuroprotective agent for PD treatment was determined. METHODS: The hemi-parkinsonian model was used to investigate the protective and therapeutic effects of honokiol on motor dysfunctions and dopaminergic neurodegeneration in mice, with a single unilateral striatal injection of 6-hydroxydopamine (6-OHDA). RESULTS: One day after 6-OHDA-induced lesion, the mice exhibited spontaneous ipsilateral turning, motor imbalance, and incoordination which were mild with a single administration of honokiol prior to 6-OHDA injection. Thereafter, honokiol was continually applied daily for 14 days, which ameliorated apomorphine-induced contralateral rotation and reduced the loss of tyrosine hydroxylase-immunoreactive (TH-ir) fibers in the lesioned striatum. In addition, honokiol posttreatment, beginning on day 8 after 6-OHDA lesion, for 14 days efficiently rescued motor deficits and recovered the TH-ir neuronal loss in both the lesioned striatum and the ipsilateral substantia nigra. The 6-OHDA-induced increases in nigrostriatal expression of inducible nitric oxide synthase (iNOS) and decreases in that of nNOS were also reversed by honokiol posttreatment. CONCLUSIONS: These findings revealed that honokiol has both protective and therapeutic effects on motor impairments and dopaminergic progressive damage, at least in part through modulation of NOS signaling, in 6-OHDA-lesioned mice. Honokiol may represent a potential therapeutic candidate for the management of motor symptoms and neurodegeneration in PD.
BACKGROUND:Parkinson's disease (PD) is a progressive and profound movement disorder resulting from neurodegeneration in the nigrostriatal dopaminergic system, but current treatment neither cures nor stops PD from advancing. Based on the ability to suppress oxidative stress, excitotoxicity, and neuroinflammation, the potential of honokiol as a novel neuroprotective agent for PD treatment was determined. METHODS: The hemi-parkinsonian model was used to investigate the protective and therapeutic effects of honokiol on motor dysfunctions and dopaminergic neurodegeneration in mice, with a single unilateral striatal injection of 6-hydroxydopamine (6-OHDA). RESULTS: One day after 6-OHDA-induced lesion, the mice exhibited spontaneous ipsilateral turning, motor imbalance, and incoordination which were mild with a single administration of honokiol prior to 6-OHDA injection. Thereafter, honokiol was continually applied daily for 14 days, which ameliorated apomorphine-induced contralateral rotation and reduced the loss of tyrosine hydroxylase-immunoreactive (TH-ir) fibers in the lesioned striatum. In addition, honokiol posttreatment, beginning on day 8 after 6-OHDA lesion, for 14 days efficiently rescued motor deficits and recovered the TH-ir neuronal loss in both the lesioned striatum and the ipsilateral substantia nigra. The 6-OHDA-induced increases in nigrostriatal expression of inducible nitric oxide synthase (iNOS) and decreases in that of nNOS were also reversed by honokiol posttreatment. CONCLUSIONS: These findings revealed that honokiol has both protective and therapeutic effects on motor impairments and dopaminergic progressive damage, at least in part through modulation of NOS signaling, in 6-OHDA-lesioned mice. Honokiol may represent a potential therapeutic candidate for the management of motor symptoms and neurodegeneration in PD.
Authors: Jelena Osmanovic Barilar; Ana Knezovic; Ana Babic Perhoc; Jan Homolak; Peter Riederer; Melita Salkovic-Petrisic Journal: J Neural Transm (Vienna) Date: 2020-02-06 Impact factor: 3.575
Authors: Daria D Vaulina; Kira I Stosman; Konstantin V Sivak; Andrey G Aleksandrov; Nikolai B Viktorov; Nikolay N Kuzmich; Mariia M Kiseleva; Olga F Kuznetsova; Natalia A Gomzina Journal: Molecules Date: 2021-11-01 Impact factor: 4.411