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

Susanta Mondal,Kalipada Pahan,Robyn Klein

doi:10.1371/journal.pone.0116566

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.

Highlights

Regulatory T cells (Tregs) are regarded as the master regulator of immune responses because this cell type maintains the homeostasis between immune activation and immune suppressionPLOS ONE | DOI:10.1371/journal.pone.0116566 January 8, 2015Suppression of EAE by Cinnamon [1, 2]
Chinese cinnamon (Cinnamonum cassia) and original Ceylon cinnamon (Cinnamonum verum or Cinnamonum zylencum) are two major types of cinnamon that are available in the US
By mass spectrometric analysis, we have found that Cinnamonum verum is much more pure than Cinnamonum cassia [15]

Summary

Introduction

Regulatory T cells (Tregs) are regarded as the master regulator of immune responses because this cell type maintains the homeostasis between immune activation and immune suppressionPLOS ONE | DOI:10.1371/journal.pone.0116566 January 8, 2015Suppression of EAE by Cinnamon [1, 2]. Regulatory T cells (Tregs) are regarded as the master regulator of immune responses because this cell type maintains the homeostasis between immune activation and immune suppression. Tregs suppress activation and proliferation of self-reactive T cells and thereby inhibit immune response of self-reactive T cells against self-antigens [1, 2]. Tregs are characterized by the presence of transcription factor forkhead box p3 (Foxp3) and Foxp3+ CD4+CD25+ T cells are considered as the most common phenotype of Tregs [1, 3]. Tregs are able to suppress self-reactive T cells. During autoimmune pathogenesis, the immune system is dysregulated, resulting in a substantial decrease in the activity and the number of Tregs, and thereby leading to proliferation of self-reactive T cells and subsequent autoimmune attack

Methods

Results

Conclusion