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

doi:10.1016/j.taap.2017.01.019

	Amentoflavone protects dopaminergic neurons in MPTP-induced Parkinson's disease model mice through PI3K/Akt and ERK signaling pathways
	Cao, Qin; Qin, Liyue; Huang, Fei; Wang, Xiaoshuang; Yang, Liu; Shi, Hailian; Wu, Hui; Zhang, Beibei; Chen, Ziyu; Wu, Xiaojun
刊名	Toxicology and applied pharmacology
	2017-03-15
卷号	319 页码:80-90
ISSN号	1096-0333
DOI	10.1016/j.taap.2017.01.019
文献子类	Article
英文摘要	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.
语种	英语
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/266502]
专题	中国科学院上海药物研究所
通讯作者	Huang, Fei; Wu, Xiaojun
作者单位	The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Complex Prescriptions, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, China
推荐引用方式 GB/T 7714	Cao, Qin,Qin, Liyue,Huang, Fei,et al. Amentoflavone protects dopaminergic neurons in MPTP-induced Parkinson's disease model mice through PI3K/Akt and ERK signaling pathways[J]. Toxicology and applied pharmacology,2017,319:80-90.
APA	Cao, Qin.,Qin, Liyue.,Huang, Fei.,Wang, Xiaoshuang.,Yang, Liu.,...&Wu, Xiaojun.(2017).Amentoflavone protects dopaminergic neurons in MPTP-induced Parkinson's disease model mice through PI3K/Akt and ERK signaling pathways.Toxicology and applied pharmacology,319,80-90.
MLA	Cao, Qin,et al."Amentoflavone protects dopaminergic neurons in MPTP-induced Parkinson's disease model mice through PI3K/Akt and ERK signaling pathways".Toxicology and applied pharmacology 319(2017):80-90.