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Up-Regulation of Neurotrophic Factors by Cinnamon and its Metabolite Sodium Benzoate: Therapeutic Implications for Neurodegenerative Disorders

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Abstract

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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Acknowledgments

This study was supported by grants from Alzheimer’s Association (IIRG-12-241179) and NIH (AT6681). The authors would like to thank Dr. Yang Yuan for assistance with the pharmacokinetics analysis.

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Authors do not have any conflict of interest.

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Authors and Affiliations

  1. Department of Neurological Sciences, Rush University Medical Center, 1735 West Harrison St, Suite 320, Chicago, IL, 60612, USA

    Arundhati Jana, Khushbu K. Modi, Avik Roy & Kalipada Pahan

  2. Research Resources Center, University of Illinois, Chicago, IL, USA

    John A. Anderson

  3. Department of Medicinal Chemistry and Pharmacognosy, University of Illinois, Chicago, IL, USA

    Richard B. van Breemen

Authors
  1. Arundhati Jana
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  2. Khushbu K. Modi
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  3. Avik Roy
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  5. Richard B. van Breemen
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  6. Kalipada Pahan
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Correspondence to Kalipada Pahan.

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Jana, A., Modi, K.K., Roy, A. et al. Up-Regulation of Neurotrophic Factors by Cinnamon and its Metabolite Sodium Benzoate: Therapeutic Implications for Neurodegenerative Disorders. J Neuroimmune Pharmacol 8, 739–755 (2013). https://doi.org/10.1007/s11481-013-9447-7

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  • DOI: https://doi.org/10.1007/s11481-013-9447-7

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