Multifunction of Chrysin in Parkinson's Model: Anti-Neuronal Apoptosis, Neuroprotection via Activation of MEF2D, and Inhibition of Monoamine Oxidase-B
Multifunction of Chrysin in Parkinson's Model: Anti-Neuronal Apoptosis, Neuroprotection via Activation of MEF2D, and Inhibition of Monoamine Oxidase-B
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DOI：
10.1021/acs.jafc.6b01707
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发表时间：
2016-07-06
影响因子：
6.1
通讯作者：
Zhang, Zaijun
中科院分区：
文献类型：
--
作者：
Guo, Baojian;Zheng, Chengyou;Zhang, Zaijun
胡萝卜素是一种存在于多种植物中的类黄酮化合物，由于其对一般人类健康和减轻神经系统疾病的有益作用而被用作膳食补充剂。然而，白杨素的神经保护机制尚未完全阐明，白杨素对帕金森病（PD）模型的体内作用尚未研究。研究表明白杨素通过逆转Bcl-2、Box和caspase 3的表达失调来保护初级颗粒神经元免受1-甲基-4-苯基吡啶离子的损伤-通过抗凋亡。该机制还涉及通过调节AKT-GSK 3 β信号来激活转录因子肌细胞增强因子2D（MEF 2D）。在这种PD体内模型中，白杨素挽救了小鼠多巴胺能神经元的丢失，并缓解了1-甲基-4-苯基-1，2，3，6-四氢吡啶引起的小鼠多巴胺水平下降。此外，白杨素显着抑制单胺氧化酶-B的活性在体外和体内。总之，白杨素对PD发挥有益作用，可能通过多靶点机制，包括抗神经元凋亡，AKT-GSK 3 β/MEF 2D通路的激活和MAO-B活性的抑制。
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.