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      Vitexin protects dopaminergic neurons in MPTP-induced Parkinson’s disease through PI3K/Akt signaling pathway

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          Parkinson’s disease (PD) is a progressive neurodegenerative disease which is characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc).


          In this study, the neuroprotective effect of vitexin (Vit), a flavonoid compound isolated from Crataegus pinnatifida Bunge was examined in PD models both in vitro and in vivo.


          On SH-SY5Y cells, methyl-4-phenylpyridine (MPP +) treatment suppressed cell viability, induced apoptosis, and increased Bax/Bcl-2 ratio and caspase-3 activity. However, Vit improved these parameters induced by MPP + treatment significantly. Further study disclosed that Vit enhanced the phosphorylation of PI3K and Akt which was downregulated by MPP + in SH-SY5Y cells, the effect of which could be blocked by PI3K inhibitor LY294002 and activated by PI3K activator IGF-1. Moreover, results from the pole test and traction test suggested that Vit pretreatment prevented bradykinesia and alleviated the initial lesions caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in MPTP-treated mouse PD model. Vit also enhanced the activation of PI3K and Akt and suppressed the ratio of Bax/Bcl-2 and caspase-3 activity in MPTP-treated mice.


          Taken together, this study demonstrated that Vit protected dopaminergic neurons against MPP +/MPTP-induced neurotoxicity through the activation of PI3K/Akt signaling pathway. Our findings may facilitate the clinical application of Vit in the therapy of PD.

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          Most cited references 26

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          Apoptosis in neurodegenerative disorders.

           M Mattson (2000)
          Neuronal death underlies the symptoms of many human neurological disorders, including Alzheimer's, Parkinson's and Huntington's diseases, stroke, and amyotrophic lateral sclerosis. The identification of specific genetic and environmental factors responsible for these diseases has bolstered evidence for a shared pathway of neuronal death--apoptosis--involving oxidative stress, perturbed calcium homeostasis, mitochondrial dysfunction and activation of cysteine proteases called caspases. These death cascades are counteracted by survival signals, which suppress oxyradicals and stabilize calcium homeostasis and mitochondrial function. With the identification of mechanisms that either promote or prevent neuronal apoptosis come new approaches for preventing and treating neurodegenerative disorders.
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            Parkinson's disease.

             Bobby Thomas,  M. Beal (2007)
            Parkinson's disease (PD) is a chronic progressive neurodegenerative movement disorder characterized by a profound and selective loss of nigrostriatal dopaminergic neurons. Clinical manifestations of this complex disease include motor impairments involving resting tremor, bradykinesia, postural instability, gait difficulty and rigidity. Current medications only provide symptomatic relief and fail to halt the death of dopaminergic neurons. A major hurdle in development of neuroprotective therapies are due to limited understanding of disease processes leading to death of dopaminergic neurons. While the etiology of dopaminergic neuronal demise is elusive, a combination of genetic susceptibilities and environmental factors seems to play a critical role. The majority of PD cases are sporadic however, the discovery of genes linked to rare familial forms of disease (encoding alpha-synuclein, parkin, DJ-1, PINK-1 and LRRK2) and studies from experimental animal models has provided crucial insights into molecular mechanisms in disease pathogenesis and identified probable targets for therapeutic intervention. Recent findings implicate mitochondrial dysfunction, oxidative damage, abnormal protein accumulation and protein phosphorylation as key molecular mechanisms compromising dopamine neuronal function and survival as the underlying cause of pathogenesis in both sporadic and familial PD. In this review we provide an overview of the most relevant findings made by the PD research community in the last year and discuss how these significant findings improved our understanding of events leading to nigrostriatal dopaminergic degeneration, and identification of potential cell survival pathways that could serve as targets for neuroprotective therapies in preventing this disabling neurological illness.
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              The neuroprotective potential of flavonoids: a multiplicity of effects.

              Flavonoids exert a multiplicity of neuroprotective actions within the brain, including a potential to protect neurons against injury induced by neurotoxins, an ability to suppress neuroinflammation, and the potential to promote memory, learning and cognitive function. These effects appear to be underpinned by two common processes. Firstly, they interact with critical protein and lipid kinase signalling cascades in the brain leading to an inhibition of apoptosis triggered by neurotoxic species and to a promotion of neuronal survival and synaptic plasticity. Secondly, they induce beneficial effects on the vascular system leading to changes in cerebrovascular blood flow capable of causing angiogenesis, neurogenesis and changes in neuronal morphology. Through these mechanisms, the consumption of flavonoid-rich foods throughout life holds the potential to limit neurodegeneration and to prevent or reverse age-dependent loses in cognitive performance. The intense interest in the development of drugs capable of enhancing brain function means that flavonoids may represent important precursor molecules in the quest to develop of a new generation of brain enhancing drugs.

                Author and article information

                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                16 March 2018
                : 12
                : 565-573
                Department of Neurology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China
                Author notes
                Correspondence: Ming Hu, Department of Neurology, Shenzhen Hospital, Southern Medical University, 1333 Xinhu Road, Shenzhen, Bao’an District, Guangdong Province 518100, China, Tel +86 755 2336 0593, Email huminggdsz@ 123456163.com
                © 2018 Hu et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Original Research

                Pharmacology & Pharmaceutical medicine

                neuroprotective, pi3k/akt, parkinson’s disease, mptp, vitexin


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