Amentoflavone protects dopaminergic neurons in MPTP-induced Parkinson's disease model mice through PI3K/Akt and ERK signaling pathways.

Parkinson's disease (PD) is characterized by the progressive degeneration of dopaminergic neurons in substantia nigra pars compacta (SNpc). Mitochondrial dysfunction and cell apoptosis are suggested to be actively involved in the pathogenesis of PD. In the present study, the neuroprotective effect of amentoflavone (AF), a naturally occurring biflavonoid from Selaginella tamariscina, was examined in PD models both in vitro and in vivo. On SH-SY5Y cells, AF treatment dose-dependently reduced 1-methyl-4-phenylpyridinium (MPP+)-induced nuclear condensation and loss of cell viability without obvious cytotoxicity. It inhibited the activation of caspase-3 and p21 but increased the Bcl-2/Bax ratio. Further study disclosed that AF enhanced the phosphorylation of PI3K, Akt and ERK1/2 down-regulated by MPP+ in SH-SY5Y cells, the effect of which could be blocked by LY294002, the inhibitor of PI3K. Consistently, AF alleviated the behavioral deterioration in pole and traction tests and rescued the loss of dopaminergic neurons in SNpc and fibers in striatum in methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced mice. It also could enhance the activation of PI3K and Akt as well as Bcl-2/Bax ratio in SN. Moreover, AF alleviated gliosis as well as the gene expression levels of IL-1β and iNOS in SN. Collectively, these results suggested that AF protected dopaminergic neurons against MPTP/MPP+-induced neurotoxicity, which might be mediated through activation of PI3K/Akt and ERK signaling pathways in dopaminergic neurons and attenuation of neuroinflammation.

Cao Q ，Qin L ，Huang F ，Wang X ，Yang L ，Shi H ，Wu H ，Zhang B ，Chen Z ，Wu X ... -  《-》

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

Hu M ，Li F ，Wang W 《Drug Design Development and Therapy》

Neuroprotective properties of icariin in MPTP-induced mouse model of Parkinson's disease: Involvement of PI3K/Akt and MEK/ERK signaling pathways.

Epimedium sagittatum is a traditional Chinese herb normally which is used to treat the osteoporosis, cardiovascular dysfunction, and to improve neurological and sexual function in China, Korea and Japan. Icariin is the major active ingredient in Epimedium sagittatum. In the present research, we examined the neuroprotective effects of icariin on dopaminergic neurons and the possible mechanisms in a mouse model of Parkinson's disease (PD). Ovariectomized PD mice were treated with vehicle or icariin (3 days before MPTP injections) with or without the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 or mitogen-activated protein kinase kinase (MEK) inhibitor PD98059. The dopamine (DA) content in the striatum was studied by HPLC. Western blot was used to determine the protein expressions of Bcl-2, Bax and Caspase 3 in the striatum. The numbers of tyrosine hydroxylase-immunoreactive (TH-IR) neurons in the substantial nigra pars compacta (SNpc) were assessed by immunohistochemistry. The activation of Akt and ERK by icariin were detected in doparminergic MES23.5 cells. Icariin pretreatment could ameliorate the decreased striatum DA content and the loss of TH-IR neurons in the SNpc induced by MPTP. The MPTP-induced changes of Bcl-2, Bax and caspase 3 protein expressions in the striatum could be reversed by icariin pretreatment. Blockade of PI3K/Akt or MEK/ERK signaling pathway by LY294002 or PD98059 could attenuate the increase of DA content in the striatum and TH-IR in the SNpc induced by icariin in PD mice model. Additionally, icariin treatment alone significantly induced the phosphorylation of Akt and ERK in a time dependent pattern in dopaminergic MES 23.5 cells. These effects were abolished by co-treatment with LY294002 or PD98059. These data demonstrated that icariin has neuroprotective effect on dopaminergic neurons in PD mice model and the potential mechanisms might be related to PI3K/Akt and MEK/ERK pathways.

Chen WF ，Wu L ，Du ZR ，Chen L ，Xu AL ，Chen XH ，Teng JJ ，Wong MS ... -  《-》

Neuroprotective Effects of the DPP4 Inhibitor Vildagliptin in In Vivo and In Vitro Models of Parkinson's Disease.

Pariyar R ，Bastola T ，Lee DH ，Seo J ... -  《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

Neuroprotection by Paeoniflorin in the MPTP mouse model of Parkinson's disease.

Paeoniflorin (PF) is a major bioactive ingredient in Radix Paeonia alba roots that has low toxicity and has been shown to have neuroprotective effects. Our in vitro experiments suggested that PF affords a significant neuroprotective effect against MPP+-induced damage and apoptosis in PC12 cells through Bcl-2/Bax/caspase-3 pathway. The objectives of the present study were to explore the potential neuroprotective effect of PF in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-treated mouse model of Parkinson's disease (PD). Our results demonstrated that PF treatment ameliorated the behavioral deficits of "in spontaneous motor activity and latency to fall of the rotarod test", and reduced dopaminergic cell loss that were induced by MPTP in a dose-dependent manner in an in vivo model of PD. In addition, we found that treatment of PF protected dopaminergic neurons by preventing MPTP-induced decreases in striatal and substantia nigra dopaminergic transporter (DAT) and tyrosine hydroxylase (TH) protein levels, and by changing dopamine catabolism and inhibiting dopamine turnover. Furthermore, it was also associated with up-regulation of the Bcl-2/BAD ratio, and inhibition of the activation of caspase-9 and caspase-3. These results showed that PF promoted dopamine neuron survival in vivo due to the MAO-B inhibition, and the PI3K/Akt signaling pathway may have mediated the protection of PF against MPTP, suggesting that PF treatment might represent a neuroprotective treatment for PD.

Zheng M ，Liu C ，Fan Y ，Yan P ，Shi D ，Zhang Y ... -  《-》