7,8‐dihydroxyflavone Ameliorates Motor Deficits Via Suppressing <i>α</i>‐synuclein Expression and Oxidative Stress in the <scp>MPTP</scp>‐induced Mouse Model of Parkinson's Disease

Li, Xiaohuan; Dai, Cuiqiong; Chen, Long; Zhou, Weitao; Han, Hyounkoo; Dong, Zhifang

doi:10.1111/cns.12555

Cited by 50 publications

(36 citation statements)

References 46 publications

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“…Up until now, the behavioral assessments in the subacute MPTP mouse model are still controversial. Many studies have described motor defects [12][13][14] , while others have proven that the model hardly mimics the movement disorder of PD and may even induce hyperactivity in animals [10,15,16] . Here, in our research, subacute MPTP treatment failed to cause typical movement defects in spite of the serious damage to the dopaminergic neurons and the remarkable decrease in DA content.…”

Section: Discussionmentioning

confidence: 99%

Reassessment of subacute MPTP-treated mice as animal model of Parkinson's disease

et al. 2017

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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model remains the most commonly used animal model of Parkinson's disease (PD). There are three MPTP-treatment schemes: acute, subacute and chronic. Considering the advantages of the period and similarity to PD, the subacute model was often chosen to assess the validity of new candidates, but the changes caused by the subacute MPTP treatment and the appropriate positive control for this model remain to be further confirmed. The aim of this study was: to estimate the value of the subacute MPTP mouse model in aspects of behavioral performance, biochemical changes and pathological abnormalities, and to find effective positive drugs. Male C57BL/6 mice were injected with MPTP (30 mg·kg·d, ip) for 5 consecutive days. Three days before MPTP injection, the mice were orally administered selegiline (3 mg·kg·d), pramipexole (3 mg·kg·d), or medopar (100 mg·kg·d) for 18 days. Behavioral performance was assessed in the open field test, pole test and rotarod test. Neurotransmitters in the striatum were detected using HPLC. Protein levels were measured by Western blot. Pathological characteristics were examined by immunohistochemistry. Ultrastructure changes were observed by electron microscopy. The subacute MPTP treatment did not induce evident motor defects despite severe injuries in the dopaminergic system. Additionally, MPTP significantly increased the α-synuclein levels and the number of astrocytes in the striatum, and destroyed the blood-brain barrier (BBB) in the substantia nigra pars compacta. Both selegiline and pramipexole were able to protect the mice against MPTP injuries. We conclude that the subacute MPTP mouse model does not show visible motor defects; it is not enough to evaluate the validity of a candidate just based on behavioral examination, much attention should also be paid to the alterations in neurotransmitters, astrocytes, α-synuclein and the BBB. In addition, selegiline or pramipexole is a better choice than medopar as an effective positive control for the subacute MPTP model.

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Section: Discussionmentioning

confidence: 99%

Reassessment of subacute MPTP-treated mice as animal model of Parkinson's disease

et al. 2017

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“…In another related study using the fluid percussion injury (FPI) model, treatment with 7,8-DHF successfully restored TrkB signaling and memory function in the Barnes maze test [109]. 7,8-DHF also exhibited beneficial effects in the treatment of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) [110][111][112][113][114]. Recently, a derivative of 7,8-DHF, namely, BrAD-R13, was approved by the FDA for use in clinical trials for the treatment of mild to moderate AD.…”

Section: Improvement Of Bdnf Delivery and The Development Of New Trkbmentioning

confidence: 99%

Brain-Derived Neurotrophic Factor and Its Potential Therapeutic Role in Stroke Comorbidities

et al. 2020

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With the rise in the aging global population, stroke comorbidities have become a serious health threat and a tremendous economic burden on human society. Current therapeutic strategies mainly focus on protecting neurons from cytotoxic damage at the acute phase upon stroke onset, which not only is a difficult way to ameliorate stroke symptoms but also presents a challenge for the patients to receive effective treatment in time. The brain-derived neurotrophic factor (BDNF) is the most abundant neurotrophin in the adult brain, which possesses a remarkable capability to repair brain damage. Recent promising preclinical outcomes have made BDNF a popular late-stage target in the development of novel stroke treatments. In this review, we aim to summarize the latest progress in the understanding of the cellular/molecular mechanisms underlying stroke pathogenesis, current strategies and difficulties in drug development, the mechanism of BDNF action in poststroke neurorehabilitation and neuroplasticity, and recent updates in novel therapeutic methods.

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“…Xiao-Huan Li et al reported a biological evaluation of DHF molecule that suppressed ASN expression and oxidative stress against MPTP induced Parkinson mice model 15 . The 7,8-Dihydroxyflavone (DHF) is a member of the flavonoid family, and highly present in vegetables and fruits.…”

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confidence: 99%

Design and Molecular dynamic Investigations of 7,8-Dihydroxyflavone Derivatives as Potential Neuroprotective Agents Against Alpha-synuclein

Mohankumar

Chandramohan

Lalithamba

et al. 2020

Sci Rep

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Parkinson's disease (PD) is the second most common neurodegenerative disorder caused due to loss of dopaminergic neurons in substantia nigra pars compacta, which occurs the presence of Lewy bodies made up of Alpha-synuclein (ASN) aggregation resulting in neuronal death. This study aims to identify potent 7,8-Dihydroxyflavone (DHF) derivatives to inhibit the ASN aggregation from in silico analysis. Molecular docking study reveals that carbamic ester derivatives of DHF [DHF-BAHPC (8q), DHF-BAHPEC (8s), DHF-BAHEC (8p), DHF-BDOPC (8c), DHF-BAPEC (8n) and DHF-BAMC (8h)] have good binding affinity towards ASN, when compared with DHF and L-DOPA; their docking score values are −16.3120, −16.1875, −15.2223, −14.3118, −14.2893, -14.2810, −14.0383, and −9.1560 kcal/ mol respectively.The in silico pharmacological evaluation shows that these molecules exhibit the druglikeness and ADMET properties. Molecular dynamics simulation confirms the stability of the molecules with ASN. The intermolecular interaction analyzed under the dynamic condition, allows to identify the candidate which potentially inhibits ASN aggregation. Hence, we propose that DHF derivatives are the potential lead drug molecules and preclinical studies are needed to confirm the promising therapeutic ability against PD.Parkinson's disease (PD) is a common neurodegenerative disorder characterized by impairment of motor functions due to complete loss of dopamine in the midbrain. Clinically, PD characterized by behavioral impairments such as rigidity, tremor, postural instability and bradykinesia 1 . Alpha-synuclein (ASN), a PD associated protein, misfolds and accumulates in the brain through protein aggregation. Post-mortem studies showed that these aggregated filamentous termed as a Lewy body, the neurotoxicity is a main factor involved in PD and other disorders such as Alzheimer and Prion disease 2 . Studies report that the loss of dopaminergic neurons in PD is partly due to the overexpression of ASN in the cytoplasm of neurons. ASN expression increases in the substantia nigra with the response of age in rhesus monkeys and humans 3 . The unfolded ASN protein does not have a secondary structure under the physiological condition. However, changes in various environmental factors (agitation, ion strength, pH) induces the formation of amyloid-like fibrils and ASN aggregates in vitro 4 . Comparatively, ASN has more cytotoxicity than the amyloid proteins, which generate amyloid-like fibrils 5 . To prevent the aggregation

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7,8‐dihydroxyflavone Ameliorates Motor Deficits Via Suppressing α‐synuclein Expression and Oxidative Stress in the MPTP‐induced Mouse Model of Parkinson's Disease

Cited by 50 publications

References 46 publications

Reassessment of subacute MPTP-treated mice as animal model of Parkinson's disease

Reassessment of subacute MPTP-treated mice as animal model of Parkinson's disease

Brain-Derived Neurotrophic Factor and Its Potential Therapeutic Role in Stroke Comorbidities

Design and Molecular dynamic Investigations of 7,8-Dihydroxyflavone Derivatives as Potential Neuroprotective Agents Against Alpha-synuclein

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