Vitexin protects dopaminergic neurons in MPTP-induced Parkinson&amp;rsquo;s disease through PI3K/Akt signaling pathway

Hu, Ming; Li, Fangming; Wang, Weidong

doi:10.2147/dddt.s156920

Cited by 88 publications

(55 citation statements)

References 29 publications

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“…The mechanism involved the augmentation of the phosphorylation of Akt, GSK-3β and Erk pathway, confirmed by the disappearance of the cytoprotective effects of sulfuretin following the administration of PI3K/Akt and Erk inhibitors ( 78 ). Vitexin, a glucoside derivative of apigenin and several other flavonoids had similar protective effects on cell and mouse models of PD ( 79 ).…”

Section: Neurological Diseasesmentioning

confidence: 99%

The Akt pathway in oncology therapy and beyond (Review)

et al. 2018

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Protein kinase B (Akt), similar to many other protein kinases, is at the crossroads of cell death and survival, playing a pivotal role in multiple interconnected cell signaling mechanisms implicated in cell metabolism, growth and division, apoptosis suppression and angiogenesis. Akt protein kinase displays important metabolic effects, among which are glucose uptake in muscle and fat cells or the suppression of neuronal cell death. Disruptions in the Akt-regulated pathways are associated with cancer, diabetes, cardiovascular and neurological diseases. The regulation of the Akt signaling pathway renders Akt a valuable therapeutic target. The discovery process of Akt inhibitors using various strategies has led to the identification of inhibitors with great selectivity, low side-effects and toxicity. The usefulness of Akt emerges beyond cancer therapy and extends to other major diseases, such as diabetes, heart diseases, or neurodegeneration. This review presents key features of Akt structure and functions, and presents the progress of Akt inhibitors in regards to drug development, and their preclinical and clinical activity in regards to therapeutic efficacy and safety for patients.

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Section: Neurological Diseasesmentioning

confidence: 99%

The Akt pathway in oncology therapy and beyond (Review)

et al. 2018

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“…Pole Test. Bradykinesia in PD mouse models is usually evaluated by this test [30]. The test was done after the last MPTP injection was given.…”

Section: Experimental Animalsmentioning

confidence: 99%

Neuroprotective Effect of Chlorogenic Acid on Mitochondrial Dysfunction-Mediated Apoptotic Death of DA Neurons in a Parkinsonian Mouse Model

Singh

Nand

Birla

et al. 2020

Oxidative Medicine and Cellular Longevity

123

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Mitochondrial dysfunction and oxidative stress characterize major factors involved in the activation of complex processes corresponding to apoptosis-mediated neuronal senescence of dopaminergic neurons (DA) in Parkinson’s disease (PD). Here, we evaluated the molecular mechanisms participating in the treatment of a 1-methyl-4-phenyl-1,2,3,6-tetrahydopyridine- (MPTP-) intoxicated PD mouse model in response to chlorogenic acid (CGA). The results indicate that CGA treatment significantly improved the motor coordination of the MPTP-intoxicated mice. CGA also alleviated the fall in activity of mitochondrial complexes I, IV, and V in accordance with ameliorating the level of superoxide dismutase and mitochondrial glutathione in the midbrain of MPTP-induced mice. CGA inhibited the activation of proapoptotic proteins including Bax and caspase-3, while elevating the expression of antiapoptotic protein like Bcl-2 consequently preventing the MPTP-mediated apoptotic cascade. The study also revealed the improved phosphorylation state of Akt, ERK1/2, and GSK3β which was downregulated as an effect of MPTP toxicity. Our findings signify that CGA may possess pharmacological properties and contribute to neuroprotection against MPTP induced toxicity in a PD mouse model associated with phosphorylation of GSK3β via activating Akt/ERK signalling in the mitochondrial intrinsic apoptotic pathway. Thus, CGA treatment may arise as a potential therapeutic candidate for mitochondrial-mediated apoptotic senescence of DA neurons in PD.

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“…On the 5th day after MPTP treatment, the mice began behavioral training once per day for 3 days. Protocols of behavioral tests (pole descent test and traction test) have been described in previous studies [30,31]. The pole test is a useful method for evaluating bradykinesia in mouse PD models.…”

Section: Behavioral Testmentioning

confidence: 99%

Neuroprotection of Fasting Mimicking Diet on MPTP-Induced Parkinson's Disease Mice via Gut Microbiota and Metabolites

et al. 2019

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Parkinson's disease (PD) is strongly associated with life style, especially dietary habits, which have gained attention as disease modifiers. Here, we report a fasting mimicking diet (FMD), fasting 3 days followed by 4 days of refeeding for three 1-week cycles, which accelerated the retention of motor function and attenuated the loss of dopaminergic neurons in the substantia nigra in 1-methyl-4-phenyl-1,2,3,6-tetrathydropyridine (MPTP)-induced PD mice. Levels of brain-derived neurotrophic factor (BDNF), known to promote the survival of dopaminergic neurons, were increased in PD mice after FMD, suggesting an involvement of BDNF in FMD-mediated neuroprotection. Furthermore, FMD decreased the number of glial cells as well as the release of TNF-α and IL-1β in PD mice, showing that FMD also inhibited neuro-inflammation. 16S and 18S rRNA sequencing of fecal microbiota showed that FMD treatment modulated the shifts in gut microbiota composition, including higher abundance of Firmicutes, Tenericutes, and Opisthokonta and lower abundance of Proteobacteria at the phylum level in PD mice. Gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry revealed that FMD modulated the MPTP-induced lower propionic acid and isobutyric acid, and higher butyric acid and valeric acid and other metabolites. Transplantation of fecal microbiota, from normal mice with FMD treatment to antibiotic-pretreated PD mice increased dopamine levels in the recipient PD mice, suggesting that gut microbiota contributed to the neuroprotection of FMD for PD. These findings demonstrate that FMD can be a new means of preventing and treating PD through promoting a favorable gut microbiota composition and metabolites.

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

Cited by 88 publications

References 29 publications

The Akt pathway in oncology therapy and beyond (Review)

The Akt pathway in oncology therapy and beyond (Review)

Neuroprotective Effect of Chlorogenic Acid on Mitochondrial Dysfunction-Mediated Apoptotic Death of DA Neurons in a Parkinsonian Mouse Model

Neuroprotection of Fasting Mimicking Diet on MPTP-Induced Parkinson's Disease Mice via Gut Microbiota and Metabolites

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