Up-regulation of neurotrophic factors by cinnamon and its metabolite sodium benzoate: therapeutic implications for neurodegenerative disorders.
Up-regulation of neurotrophic factors by cinnamon and its metabolite sodium benzoate: therapeutic implications for neurodegenerative disorders.
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DOI：
10.1007/s11481-013-9447-7
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发表时间：
2013-06
影响因子：
6.2
通讯作者：
Pahan, Kalipada
中科院分区：
文献类型：
--
作者：
Jana, Arundhati;Modi, Khushbu K.;Roy, Avik;Anderson, John A.;van Breemen, Richard B.;Pahan, Kalipada
这项研究强调了肉桂（一种广泛使用的食品香料和调味材料）及其代谢产物苯甲酸钠（NaB）（一种广泛使用的食品防腐剂和FDA批准的抗人类尿素循环障碍药物）在增加神经营养因子水平方面的重要性[例如，脑源性神经营养因子（BDNF）和神经营养素-3（NT-3）]。NaB，而不是甲酸钠（NaFO），剂量依赖性地诱导BDNF和NT-3在原代人神经元和星形胶质细胞中的表达。有趣的是，口服肉桂粉增加了血清和脑中的NaB水平，并上调了小鼠CNS中体内这些神经营养因子的水平。因此，口服NaB而非NaFO也增加了小鼠CNS中这些神经营养因子的体内水平。NaB诱导蛋白激酶A（PKA）的激活，但不诱导蛋白激酶C（PKC），而H-89，PKA的抑制剂，消除NaB诱导的神经营养因子的增加。此外，Na B激活cAMP反应元件结合（CREB）蛋白，但不激活NF-κB，通过siRNA敲低CREB消除Na B诱导的神经营养因子表达，以及Na B募集CREB和CREB结合蛋白至BDNF启动子，表明Na B通过激活CREB发挥其神经营养作用。因此，肉桂喂养也增加了PKA的活性和磷酸化CREB在CNS中的水平。这些结果突出了肉桂及其代谢物NaB通过PKA-CREB途径的新的神经营养性质，这可能对各种神经退行性疾病有益。
This study underlines the importance of cinnamon, a widely-used food spice and flavoring material, and its metabolite sodium benzoate (NaB), a widely-used food preservative and a FDA-approved drug against urea cycle disorders in humans, in increasing the levels of neurotrophic factors [e.g., brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3)] in the CNS. NaB, but not sodium formate (NaFO), dose-dependently induced the expression of BDNF and NT-3 in primary human neurons and astrocytes. Interestingly, oral administration of ground cinnamon increased the level of NaB in serum and brain and upregulated the levels of these neurotrophic factors in vivo in mouse CNS. Accordingly, oral feeding of NaB, but not NaFO, also increased the level of these neurotrophic factors in vivo in the CNS of mice. NaB induced the activation of protein kinase A (PKA), but not protein kinase C (PKC), and H-89, an inhibitor of PKA, abrogated NaB-induced increase in neurotrophic factors. Furthermore, activation of cAMP response element binding (CREB) protein, but not NF-κB, by NaB, abrogation of NaB-induced expression of neurotrophic factors by siRNA knockdown of CREB and the recruitment of CREB and CREB-binding protein to the BDNF promoter by NaB suggest that NaB exerts its neurotrophic effect through the activation of CREB. Accordingly, cinnamon feeding also increased the activity of PKA and the level of phospho-CREB in vivo in the CNS. These results highlight a novel neutrophic property of cinnamon and its metabolite NaB via PKA – CREB pathway, which may be of benefit for various neurodegenerative disorders.
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DOI：
10.4049/jimmunol.1102624
发表时间：
2012-07-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Corbett GT;Roy A;Pahan K
通讯作者：
Pahan K
DOI：
10.1523/jneurosci.1243-10.2010
发表时间：
2010-09-22
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Jana A;Pahan K
通讯作者：
Pahan K
影响因子：
5.3
作者：
Porritt, MJ;Batchelor, PE;Howells, DW
通讯作者：
Howells, DW
影响因子：
4.4
作者：
Jana, Malabendu;Jana, Arundhati;Pahan, Kalipada
通讯作者：
Pahan, Kalipada
影响因子：
6.2
作者：
Mondal, Susanta;Roy, Avik;Jana, Arundhati;Ghosh, Sankar;Kordower, Jeffrey H.;Pahan, Kalipada
通讯作者：
Pahan, Kalipada