Immunomodulatory effect of water extract of cinnamon on anti-CD3-induced cytokine responses and p38, JNK, ERK1/2, and STAT4 activation

Immunopharmacol Immunotoxicol. 2011 Dec;33(4):714-22. doi: 10.3109/08923973.2011.564185. Epub 2011 Mar 29.


Context: Cinnamon bark is a very popular herb used in traditional medicine to treat various disorders such as chronic gastric symptoms, arthritis, and the common cold.

Objective: The immunomodulatory effect of water extract of cinnamon bark (CWE) on cytokine secretion and involvement of intracellular signaling molecules in activated T cells have been examined.

Materials and methods: Mice were orally administered CWE for 7 days. Serum was obtained 90 min after intravenous injection of anti-CD3 antibody (Ab). Splenocytes were cultured with anti-CD3 Ab and CWE for cytokine expression, cell cycle, apoptotic/necrotic changes, and viability. IκBα, p38, JNK, ERK1/2, STAT4, and STAT6 were analyzed using western blotting.

Results: Administration of CWE decreased systemic levels of IFN-γ, but not the levels of IL-4 or IL-2. In vitro, CWE inhibited anti-CD3 Ab-stimulated IFN-γ and IL-4 at the mRNA and secreted protein levels. Despite its inhibition of IL-2 transcript, CWE enhanced IL-2 secretion. CWE treatment caused a reduction in the sub-G1 phase, accompanied by an increased ratio of apoptotic cells to necrotic cells. The increased IL-2 secretion by CWE was not mediated by its direct effect on CD4 T cells. CWE inhibited the activation of p38, JNK, ERK1/2, and STAT4, but not IκBα degradation or STAT6.

Discussion and conclusions: These observations provided evidence that CWE was able to down-regulate IFN-γ expression in activated T cells without altering IL-2 production, involving inhibition of p38, JNK, ERK1/2, and STAT4. Our results contribute to a better understanding of the immunomodulatory action of cinnamon bark for the application of inflammatory disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Murine-Derived / immunology
  • Antibodies, Monoclonal, Murine-Derived / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis / immunology
  • CD3 Complex*
  • Cells, Cultured
  • Cinnamomum zeylanicum / chemistry*
  • Cytokines / biosynthesis
  • Cytokines / immunology
  • Enzyme Activation / drug effects
  • Enzyme Activation / immunology
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / immunology
  • Immunologic Factors / chemistry
  • Immunologic Factors / immunology*
  • Immunomodulation / drug effects
  • Immunomodulation / immunology
  • Inflammation / drug therapy
  • Inflammation / immunology
  • Inflammation / metabolism
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • MAP Kinase Kinase 4 / immunology*
  • MAP Kinase Kinase 4 / metabolism
  • MAP Kinase Signaling System / drug effects*
  • MAP Kinase Signaling System / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mitogen-Activated Protein Kinase 3 / immunology*
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • STAT4 Transcription Factor / immunology*
  • STAT4 Transcription Factor / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • p38 Mitogen-Activated Protein Kinases / immunology*
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Antibodies, Monoclonal, Murine-Derived
  • CD3 Complex
  • Cytokines
  • Immunologic Factors
  • Plant Extracts
  • STAT4 Transcription Factor
  • Stat4 protein, mouse
  • Mitogen-Activated Protein Kinase 3
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4