Multifunction of Chrysin in Parkinson's Model: Anti-Neuronal Apoptosis, Neuroprotection via Activation of MEF2D, and Inhibition of Monoamine Oxidase-B

被引:44
作者
Guo, Baojian [1 ,2 ]
Zheng, Chengyou [1 ,2 ]
Cai, Wei [1 ,2 ]
Cheng, Jiehong [1 ,2 ]
Wang, Hongyu [1 ,2 ]
Li, Haitao [3 ,4 ]
Sun, Yewei [1 ,2 ]
Cui, Wei [5 ]
Wang, Yuqiang [1 ,2 ]
Han, Yifan [6 ]
Lee, Simon Ming-Yuen [3 ,4 ]
Zhang, Zaijun [1 ,2 ]
机构
[1] Jinan Univ, Coll Pharm, Inst New Drug Res, Guangzhou 510632, Guangdong, Peoples R China
[2] Jinan Univ, Coll Pharm, Guangzhou Key Lab Innovat Chem Drug Res Cardiocer, Guangzhou 510632, Guangdong, Peoples R China
[3] Univ Macau, State Key Lab Qual Res Chinese Med, Taipa, Macao, Peoples R China
[4] Univ Macau, Inst Chinese Med Sci, Taipa, Macao, Peoples R China
[5] Ningbo Univ, Sch Med, Ningbo 315211, Zhejiang, Peoples R China
[6] Hong Kong Polytech Univ, Inst Modern Chinese Med, Dept Appl Biol & Chem Technol, Hong Kong, Hong Kong, Peoples R China
基金
美国国家科学基金会;
关键词
chrysin; Parkinson's disease; neuroprotection; MEF2D; MAO-B; CEREBELLAR GRANULE NEURONS; MYOCYTE ENHANCER FACTOR-2; SURVIVAL FACTOR MEF2D; SPINAL-CORD-INJURY; OXIDATIVE STRESS; IN-VITRO; FLAVONOID CHRYSIN; GENE-EXPRESSION; RAT MODEL; DISEASE;
D O I
10.1021/acs.jafc.6b01707
中图分类号
S [农业科学];
学科分类号
09 ;
摘要
Chrysin, a flavonoid compound existing in several plants, is applied as a dietary supplement because of its beneficial effects on general human health and alleviation of neurological disorders. However, mechanisms underlying neuroprotection of chrysin has not been fully elucidated, and the effects of chrysin on the Parkinson's disease (PD) model in vivo have not been investigated. It is here shown that chrysin protects primary granular neurons against 1-methyl-4-phenylpyridinium ion insult-via antiapoptosis by reversing the dysregulated expression of Bcl-2, Box, and caspase 3. The mechanisms also involved activating transcriptional factor myocyte enhancer factor 2D (MEF2D) via regulation of AKT-GSK3 beta signaling. In this in-vivo model of PD, chrysin rescued the dopaminergic neurons loss and alleviated the decrease in dopamine level induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice. Moreover, chrysin markedly inhibited monoamine oxidase-B activity in vitro and in vivo. In conclusion, chrysin exerts beneficial effects to PD, possibly through multitarget mechanisms including antineuronal apoptosis, activation of the AKT-GSK3 beta/MEF2D pathway, and inhibition of the MAO-B activity.
引用
收藏
页码:5324 / 5333
页数:10
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