Original Article
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Feb 28, 2011; 17(8): 976-986
Published online Feb 28, 2011. doi: 10.3748/wjg.v17.i8.976
Cinnamon extract suppresses experimental colitis through modulation of antigen-presenting cells
Ho-Keun Kwon, Ji-Sun Hwang, Choong-Gu Lee, Jae-Seon So, Anupama Sahoo, Chang-Rok Im, Won Kyung Jeon, Byoung Seob Ko, Sung Haeng Lee, Zee Yong Park, Sin-Hyeog Im
Ho-Keun Kwon, Ji-Sun Hwang, Choong-Gu Lee, Jae-Seon So, Anupama Sahoo, Zee Yong Park, Sin-Hyeog Im, School of Life Sciences and Immune Synapse Research Center, Gwangju Institute of Science and Technology, Gwangju 500-712, South Korea
Chang-Rok Im, Global leader program, Bugil Academy, Cheonan, Gyeonggido 330-941, South Korea
Won Kyung Jeon, Byoung Seob Ko, Korea Institute of Oriental Medicine, Daejeon 305-811, South Korea
Sung Haeng Lee, Chosun University School of Medicine, Gwangju 501-759, South Korea
Author contributions: Kwon HK performed the majority of experiments; Hwang JS, Lee CG and So JS performed TNBS-induced colitis and data analysis; Sahoo A and Im CR gave help with manuscript correction; Jeon WK, Ko BS and Lee SH prepared water soluble fractions of cinnamon extract and performed HPLC and MALDI analysis for quality control; Park ZY and Im SH designed and financed this study.
Supported by Grants from the BioGreen 21 Program, Rural Development Administration (PJ007054), Regional Technology Innovation Program of the MOCIE (RTI05-01-01) and by Korea Healthcare Technology R&D Project, Ministry of Health and Welfare (A080588-20)
Correspondence to: Dr. Sin-Hyeog Im, School of Life Sciences and Immune Synapse Research Center, Gwangju Institute of Science and Technology, Gwangju 500-712, South Korea. imsh@gist.ac.kr
Telephone: +82-62-7152503 Fax: +82-62-7152484
Received: September 20, 2010
Revised: November 25, 2010
Accepted: December 2, 2010
Published online: February 28, 2011
Abstract

AIM: To investigate the anti-inflammatory effects of cinnamon extract and elucidate its mechanisms for targeting the function of antigen presenting cells.

METHODS: Cinnamon extract was used to treat murine macrophage cell line (Raw 264.7), mouse primary antigen-presenting cells (APCs, MHCII+) and CD11c+ dendritic cells to analyze the effects of cinnamon extract on APC function. The mechanisms of action of cinnamon extract on APCs were investigated by analyzing cytokine production, and expression of MHC antigens and co-stimulatory molecules by quantitative real-time PCR and flow cytometry. In addition, the effect of cinnamon extract on antigen presentation capacity and APC-dependent T-cell differentiation were analyzed by [H3]-thymidine incorporation and cytokine analysis, respectively. To confirm the anti-inflammatory effects of cinnamon extract in vivo, cinnamon or PBS was orally administered to mice for 20 d followed by induction of experimental colitis with 2,4,6 trinitrobenzenesulfonic acid. The protective effects of cinnamon extract against experimental colitis were measured by checking clinical symptoms, histological analysis and cytokine expression profiles in inflamed tissue.

RESULTS: Treatment with cinnamon extract inhibited maturation of MHCII+ APCs or CD11c+ dendritic cells (DCs) by suppressing expression of co-stimulatory molecules (B7.1, B7.2, ICOS-L), MHCII and cyclooxygenase (COX)-2. Cinnamon extract induced regulatory DCs (rDCs) that produce low levels of pro-inflammatory cytokines [interleukin (IL)-1β, IL-6, IL-12, interferon (IFN)-γ and tumor necrosis factor (TNF)-α] while expressing high levels of immunoregulatory cytokines (IL-10 and transforming growth factor-β). In addition, rDCs generated by cinnamon extract inhibited APC-dependent T-cell proliferation, and converted CD4+ T cells into IL-10high CD4+ T cells. Furthermore, oral administration of cinnamon extract inhibited development and progression of intestinal colitis by inhibiting expression of COX-2 and pro-inflammatory cytokines (IL-1β, IFN-γ and TNF-α), while enhancing IL-10 levels.

CONCLUSION: Our study suggests the potential of cinnamon extract as an anti-inflammatory agent by targeting the generation of regulatory APCs and IL-10+ regulatory T cells.

Keywords: Cinnamon extract; Inflammation; CD4 antigen; Antigen presenting cells; Cyclooxygenase-2; Tumor necrosis factor-α; Interleukin-10; Inflammatory bowel disease