lignans and Parkinson-Disease--Secondary

Parkinson's disease (PD) is a neurodegenerative disease characterized by loss of dopaminergic neurons in the Substantia Nigra pars compacta (SNc). The proinflammatory response can occur early in the disease, contributing to nigrostriatal degeneration. Identification of the new molecules, which are able to slow down the degenerative process associated with PD, represents one of the main interests. Recently, natural polyphenols, especially lignans, have raised attention for their anti-inflammatory, antioxidant, and estrogenic activity at a peripheral level. The aim of this study was to evaluate the central effects of chronic treatment with lignan 7-hydroxymatairesinol (HMR/lignan) on neurodegenerative, neuroinflammatory processes and motor deficits induced by a unilateral intrastriatal injection of 6-hydroxydopamine (6-OHDA) in rats to evaluate the potential neuroprotective properties of this compound.. Sprague-Dawley male rats underwent lignan (10 mg/kg) or vehicle treatment (oral) for 4 wk starting from the day of 6-OHDA injection. The degree of nigrostriatal damage was evaluated by immunohistochemistry. Moreover, we performed a quantitative and qualitative assessment of neuroinflammatory process, including phenotypic polarization of microglia and astrocytes. The motor performance was assessed by behavioral tests.. We demonstrated that chronic treatment with HMR/lignan was able to slow down the progression of degeneration of striatal dopaminergic terminals in a rat model of PD, with a consequent improvement in motor performance. Nevertheless, the anti-inflammatory effect of HMR/lignan observed in SNc was not sufficient to protect dopaminergic cells bodies.. These results suggest intriguing properties of HMR/lignan at neuroprotective and symptomatic levels in the context of PD.

Topics: Animals; Corpus Striatum; Disease Models, Animal; Dopaminergic Neurons; Lignans; Male; Neuroprotective Agents; Oxidopamine; Parkinson Disease; Parkinson Disease, Secondary; Rats; Rats, Sprague-Dawley

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.. 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).. 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.. 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.

Topics: Animals; Apomorphine; Biphenyl Compounds; Corpus Striatum; Disease Models, Animal; Lignans; Male; Mice; Microinjections; Motor Activity; Neuroprotective Agents; Nitric Oxide Synthase Type I; Nitric Oxide Synthase Type II; Oxidopamine; Parkinson Disease, Secondary; Postural Balance; Substantia Nigra; Tyrosine 3-Monooxygenase

Parkinson's disease (PD) is one of the most prevalent neurodegenerative disorders in elders. Sesamin is a lignan compound and the active constituent of sesame oil with antioxidant and anti-inflammatory properties. This study was carried out to explore the mechanisms underlying sesamin effect against unilateral striatal 6-hydroxydopamine (6-OHDA) model of PD. Intrastriatal 6-OHDA-lesioned rats were pretreated with sesamin at doses of 10 or 20mg/kg/day for one week. Sesamin at a dose of 20mg/kg attenuated motor imbalance in narrow beam test, lowered striatal level of malondialdehyde (MDA) and reactive oxygen species (ROS), improved superoxide dismutase (SOD) activity, lowered striatal caspase 3 activity and α-synuclein expression, attenuated glial fibrillary acidic protein (GFAP) immunoreactivity, depressed nigral neuronal apoptosis, and prevented damage of dopaminergic neurons using tyrosine hydroxylase (TH) immunohistochemistry. These findings reveal the reversal effect of sesamin in 6-OHDA model of PD via attenuation of apoptosis, astrogliosis, oxidative stress, and down-regulation of α-synuclein.

Topics: Animals; Apoptosis; Astrocytes; Behavior, Animal; Caspase 3; Dioxoles; Gliosis; Lignans; Male; Malondialdehyde; Neostriatum; Neuroprotective Agents; Oxidative Stress; Oxidopamine; Parkinson Disease, Secondary; Postural Balance; Rats; Rats, Wistar; Reactive Oxygen Species; Superoxide Dismutase

18F-9-Fluoropropyl-(+)-dihydrotetrabenazine [18F-FP-(+)-DTBZ] positron emission tomography (PET) has been shown to detect dopaminergic neuron loss associated with Parkinson's disease (PD) in human and neurotoxin-induced animal models. A polyphenol compound, magnolol, was recently proposed as having a potentially restorative effect in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)- or 6-hydroxydopamine-treated animal models. In this study, 18F-FP-(+)-DTBZ PET was used to determine the therapeutic efficacy of magnolol in an MPTP-PD mouse model that was prepared by giving an intraperitoneally (i.p.) daily dose of 25 mg/kg MPTP to male C57BL/6 mice for 5 consecutive days. Twenty-minute static 18F-FP-(+)-DTBZ PET scans were performed before MPTP treatment and 5 days after the termination of MPTP treatment to set up the baseline control. Half of the MPTP-treated mice then received a daily dose of magnolol (10 mg/kg dissolved in corn oil, i.p.) for 6 days. 18F-FP-(+)-DTBZ PET imaging was performed the day after the final treatment. All 18F-FP-(+)-DTBZ PET images were analysed and the specific uptake ratio (SUr) was calculated. Ex vivo autoradiography (ARG) and corresponding immunohistochemistry (IHC) studies were conducted to confirm the distribution of dopaminergic terminals in the striatum. The striatal SUr ratios of 18F-FP-(+)-DTBZ PET images for the Sham, the MPTP, and the MPTP + Magnolol-treated groups were 1.25 ± 0.05, 0.75 ± 0.06, and 1.00 ± 0.11, respectively (n = 4 for each group). The ex vivo 18F-FP-(+)-DTBZ ARG and IHC results correlated favourably with the PET imaging results. 18F-FP-(+)-DTBZ PET imaging suggested that magnolol post-treatment may reverse the neuronal damage in the MPTP-lesioned PD mice. In vivo imaging of the striatal vesicular monoamine transporter type 2 (VMAT2) distribution using 18F-FP-(+)-DTBZ animal PET is a useful method to evaluate the efficacy of therapeutic drugs i.e., magnolol, for the management of PD.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Biphenyl Compounds; Corpus Striatum; Disease Models, Animal; Fluorine Radioisotopes; Humans; Lignans; Mice; Neurons; Parkinson Disease; Parkinson Disease, Secondary; Positron-Emission Tomography; Tetrabenazine; Vesicular Monoamine Transport Proteins