Cinnamon Ameliorates Experimental Allergic Encephalomyelitis in Mice via Regulatory T Cells: Implications for Multiple Sclerosis Therapy

PLoS One. 2015 Jan 8;10(1):e0116566. doi: 10.1371/journal.pone.0116566. eCollection 2015.

Abstract

Upregulation and/or maintenance of regulatory T cells (Tregs) during an autoimmune insult may have therapeutic efficacy in autoimmune diseases. Although several immunomodulatory drugs and molecules are available, most present significant side effects over long-term use. Cinnamon is a commonly used natural spice and flavoring material used for centuries throughout the world. Here, we have explored a novel use of cinnamon powder in protecting Tregs and treating the disease process of experimental allergic encephalomyelitis (EAE), an animal model of MS. Oral feeding of cinnamon (Cinnamonum verum) powder suppresses clinical symptoms of relapsing-remitting EAE in female PLP-TCR transgenic mice and adoptive transfer mouse model. Cinnamon also inhibited clinical symptoms of chronic EAE in male C57/BL6 mice. Dose-dependent study shows that cinnamon powder at a dose of 50 mg/kg body wt/d or higher significantly suppresses clinical symptoms of EAE in mice. Accordingly, oral administration of cinnamon also inhibited perivascular cuffing, maintained the integrity of blood-brain barrier and blood-spinal cord barrier, suppressed inflammation, normalized the expression of myelin genes, and blocked demyelination in the central nervous system of EAE mice. Interestingly, cinnamon treatment upregulated Tregs via reduction of nitric oxide production. Furthermore, we demonstrate that blocking of Tregs by neutralizing antibodies against CD25 abrogates cinnamon-mediated protection of EAE. Taken together, our results suggest that oral administration of cinnamon powder may be beneficial in MS patients and that no other existing anti-MS therapies could be so economical and trouble-free as this approach.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Animals
  • Blood-Brain Barrier / metabolism
  • Cinnamomum zeylanicum / chemistry
  • Cinnamomum zeylanicum / metabolism
  • Demyelinating Diseases / pathology
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy*
  • Encephalomyelitis, Autoimmune, Experimental / epidemiology
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Female
  • Incidence
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / immunology
  • Myelin Proteolipid Protein / genetics
  • Myelin Sheath / metabolism
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Receptors, Antigen, T-Cell / genetics
  • Spinal Cord / metabolism
  • Spinal Cord / pathology
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • Th17 Cells / cytology
  • Th17 Cells / immunology
  • Th17 Cells / metabolism

Substances

  • Myelin Proteolipid Protein
  • Plant Extracts
  • Plp1 protein, mouse
  • Receptors, Antigen, T-Cell