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

Lee, Beom-Joon; Kim, Youn-Jung; Cho, Dong-Hyung; Sohn, Nak-Won; Kang, Hee

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.