Atractylon, a novel dopamine 2 receptor agonist, ameliorates Parkinsonian like motor dysfunctions in MPTP-induced mice

doi:10.1016/j.neuro.2022.01.010

	Atractylon, a novel dopamine 2 receptor agonist, ameliorates Parkinsonian like motor dysfunctions in MPTP-induced mice
	Li, Hongli 1; Wang, Fei 1; Zhou, Zhenyu 1; Jiang, Xi 1; Li, Fei 1; Feng, Yaru 1; Liu, Chuhe 1; Zhang, Yu2 ; Fan, Shengjie 1; Wu, Xiaojun 3; Huang, Cheng 1
	2022-03
发表期刊	NEUROTOXICOLOGY (IF:3.4[JCR-2023],3.6[5-Year])
ISSN	0161-813X
EISSN	1872-9711
卷号	89
发表状态	已发表
DOI	10.1016/j.neuro.2022.01.010
摘要	Background: Motor symptoms of Parkinson's disease (PD) are characterized by bradykinesia, resting tremor, rigidity, slow movement, impaired gait and postural instability, resulting from progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Atractylon is a natural furan compound in Atractylodes rhizomes, exhibiting anticancer, anti-inflammation, antiviral and gastroprotective activities, and so on. However, it is still unknown whether atractylon is beneficial to motor dysfunctions of PD.Methods: GPCR-targeted piggyBac-TANGO compound screening system, cAMP assay, and immunostaining of pCREB and BDNF were used to identify dopamine 2 receptor (DRD2) activation. The effects of atractylon on motor deficits and gait disturbances, as well as tyrosine hydroxylase (TH) in the SNpc were investigated in 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice.Results: Atractylon treatment increased the eGFP expression in dose-dependent manner in piggyBac-TANGO assay, decreased cAMP production, and enhanced the levels of p-CREB and BDNF in DRD2 highly expresseding SY-SY5Y cells. In MPTP-induced mice, atractylon improved the slow movement, diminished voluntary locomotion, and abnormal gait parameters, such as duration, cadence, average speed, step cycle, stride length, and so on. Moreover, atractylon rescued the TH positive cells in SNpc and TH positive nerve fibers in striatum.Conclusions: Atractylon could effectively activate DRD2, attenuate motor deficits and gait disorders, and protect dopaminergic neurons in MPTP-induced PD mice. Our findings stretch out the therapeutic potential of atractylon for motor symptoms of PD.
关键词	Atractylon Dopamine 2 receptor Parkinson 's disease Motor deficits Gait analysis
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收录类别	SCI ; SCIE
语种	英语
WOS研究方向	Neurosciences & Neurology ; Pharmacology & Pharmacy ; Toxicology
WOS类目	Neurosciences ; Pharmacology & Pharmacy ; Toxicology
WOS记录号	WOS:000784295800002
出版者	ELSEVIER
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/176039
专题	生命科学与技术学院_PI研究组_黄行许组
通讯作者	Wu, Xiaojun; Huang, Cheng
作者单位	1.Shanghai Univ Tradit Chinese Med, Sch Pharm, Drug Discovery Lab, Shanghai 201203, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 3.Shanghai Univ Tradit Chinese Med, Inst Chinese Mat Med, Shanghai Key Lab Cpd Chinese Med, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Li, Hongli,Wang, Fei,Zhou, Zhenyu,et al. Atractylon, a novel dopamine 2 receptor agonist, ameliorates Parkinsonian like motor dysfunctions in MPTP-induced mice[J]. NEUROTOXICOLOGY,2022,89.
APA	Li, Hongli.,Wang, Fei.,Zhou, Zhenyu.,Jiang, Xi.,Li, Fei.,...&Huang, Cheng.(2022).Atractylon, a novel dopamine 2 receptor agonist, ameliorates Parkinsonian like motor dysfunctions in MPTP-induced mice.NEUROTOXICOLOGY,89.
MLA	Li, Hongli,et al."Atractylon, a novel dopamine 2 receptor agonist, ameliorates Parkinsonian like motor dysfunctions in MPTP-induced mice".NEUROTOXICOLOGY 89(2022).