钒化合物与肉桂醛共同作用改善β淀粉样蛋白损伤的SH­SY5Y神经细胞活力

doi:10.5246/jcps.2016.10.084

中国药学(英文版) ›› 2016, Vol. 25 ›› Issue (10): 754-763.DOI: 10.5246/jcps.2016.10.084

钒化合物与肉桂醛共同作用改善β淀粉样蛋白损伤的SHSY5Y神经细胞活力

李雪¹, 白力丹¹, 董雅琼¹, 常青², 武睿², 章京^2*, 杨晓达^1,3*

1. 北京大学医学部药学院天然药物及仿生药物国家重点实验室; 化学生物学系, 北京 100191
2. 北京大学医学部基础医学院病理学系, 北京 100191
3. 国家中医药管理局中药复方解毒重点研究室, 北京 100027

收稿日期:2016-05-18 修回日期:2016-06-10 出版日期:2016-10-27 发布日期:2016-06-23
通讯作者: Tel.: +86-010-82805611, E-mail: xyang@bjmu.edu.cn, zhangjing6202@163.com
基金资助:
National Natural Science Foundation of China (Grant No. 21571006 and 21271012).

Vanadyl complexes work with cinnamaldehyde in promoting cell viability under the βamyloid burden in SHSY5Y neural cells

Xue Li¹, Lidan Bai¹, Yaqiong Dong¹, Qing Chang², Rui Wu², Jing Zhang^2*, Xiaoda Yang^1,3*

1. State Key Laboratories of Natural and Biomimetic Drugs; Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
2. Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
3. SATCM Key Laboratory of Compound Drug Detoxication at Peking University, Beijing 100027, China

Received:2016-05-18 Revised:2016-06-10 Online:2016-10-27 Published:2016-06-23
Contact: Tel.: +86-010-82805611, E-mail: xyang@bjmu.edu.cn, zhangjing6202@163.com
Supported by:
National Natural Science Foundation of China (Grant No. 21571006 and 21271012).

摘要/Abstract

摘要：

阿尔茨海默症(Alzheimer's disease, AD)是老年人群中最常见的认知障碍疾病之一。阿尔茨海默症与糖尿病(diabetes mellitus, DM)拥有某些相似的病理机制, 因此我们推测抗糖尿病钒化合物可能具有抗AD活性。本文研究了双乙酰丙酮氧钒(vanadyl acetylacetonate, VO(acac)₂)和肉桂醛(cinnamaldehyde, CA)对SH-SY5Y神经细胞及AD模型的作用。结果显示, VO(acac)₂在微摩尔浓度水平可以提高SH-SY5Y神经细胞及过表达β淀粉样蛋白(Aβ)细胞的活力; VO(acac)₂与CA的联合使用对正常和负载Aβ的神经细胞都具有加和的保护作用。更进一步实验发现, VO(acac)₂可以激活神经细胞中PPARγ-AMPK的信号转导通路, 抑制导致Tau蛋白的过度磷酸化的重要酶––GSK 3β的活化; 而CA可以恢复Aβ诱导的线粒体分裂, 从而增强线粒体功能。此外, VO(acac)₂与CA都能降低细胞内活性氧水平并抑制毒性的低分子量Aβ寡聚体形成。综上所述, VO(acac)₂能与CA协同作用, 改善β淀粉样蛋白导致的神经细胞损伤。本工作为钒金属药物的应用提示了新的发展方向。

关键词: 阿尔茨海默症, β淀粉样蛋白, SH-SY5Y细胞, 钒化合物, 肉桂醛

Abstract:

The Alzheimer’s disease (AD) is one of the common cognitive disorders in the elderly. AD shares some similar pathological characters with diabetes mellitus (DM), suggesting potential application of anti-diabetic agents, such as vanadyl complexes, in therapeutic treatment of AD. In the present work, we studied the effects of vanadyl acetylacetonate (VO(acac)₂) and cinnamaldehyde (CA) on an AD model based on SH-SY5Y neural cells. The experimental results showed that VO(acac)₂ at sub-micromolar concentrations could improve the viability of neural cells with or without increased βamyloid (Aβ) burden; and the combination of VO(acac)₂ and CA showed an additive cell protection effects. Further investigation revealed that for SH-SY5Y neural cells, VO(acac)₂ could activate PPARγ-AMPK signal transduction and inhibit GSK 3β, one of the major kinases for Tau hyperphosphorylation. Meanwhile, CA could correct the abnormal mitochondrial morphology due to Aβ-induced excessive mitochondrial fission, thus restoring/enhancing the mitochondrial function. In addition, both VO(acac)₂ and CA decreased intracellular reactive oxygen species (ROS) level and inhibited formation of toxic Aβ oligomers. Overall, VO(acac)₂ might work with CA in improving the neural cell viability under the Aβ burden, suggesting application of vanadium metallodrugs in AD treatment.

Key words: Alzheimer’s disease, βAmyloid, SH-SY5Y cells, Vanadium, Cinnamaldehyde

中图分类号:

R915

Supporting:

李雪, 白力丹, 董雅琼, 常青, 武睿, 章京, 杨晓达. 钒化合物与肉桂醛共同作用改善β淀粉样蛋白损伤的SHSY5Y神经细胞活力[J]. 中国药学(英文版), 2016, 25(10): 754-763.

Xue Li, Lidan Bai, Yaqiong Dong, Qing Chang, Rui Wu, Jing Zhang, Xiaoda Yang. Vanadyl complexes work with cinnamaldehyde in promoting cell viability under the βamyloid burden in SHSY5Y neural cells[J]. Journal of Chinese Pharmaceutical Sciences, 2016, 25(10): 754-763.

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钒化合物与肉桂醛共同作用改善β淀粉样蛋白损伤的SHSY5Y神经细胞活力

Vanadyl complexes work with cinnamaldehyde in promoting cell viability under the βamyloid burden in SHSY5Y neural cells

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钒化合物与肉桂醛共同作用改善β淀粉样蛋白损伤的SH­SY5Y神经细胞活力

Vanadyl complexes work with cinnamaldehyde in promoting cell viability under the β­amyloid burden in SH­SY5Y neural cells

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钒化合物与肉桂醛共同作用改善β淀粉样蛋白损伤的SHSY5Y神经细胞活力

Vanadyl complexes work with cinnamaldehyde in promoting cell viability under the βamyloid burden in SHSY5Y neural cells