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1.  Cinnamon extract suppresses experimental colitis through modulation of antigen-presenting cells 
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.
PMCID: PMC3057159  PMID: 21451725
Cinnamon extract; Inflammation; CD4 antigen; Antigen presenting cells; Cyclooxygenase-2; Tumor necrosis factor-α; Interleukin-10; Inflammatory bowel disease
2.  Modification of surface pretreatment of white spot lesions to improve the safety and efficacy of resin infiltration 
Korean Journal of Orthodontics  2014;44(4):195-202.
A low-viscosity resin (infiltrant) was used to inhibit the progression of white spot lesions (WSLs) and resolve associated esthetic issues. An alternative pretreatment was explored to increase the pore volume of the surface layer of the WSLs. Also, the penetration effects of the infiltrant were evaluated for various pretreatments.
Sixty two artificial lesions were fabricated on bovine teeth. As a positive control, 15% HCl gel was applied for 120 seconds. Further, 37% H3PO4 gel was applied for 30 seconds using three methods. The samples were divided as follows: H3PO4 only group, H3PO4 sponge group, and H3PO4 brush group. The acid was gently rubbed with the applicators (i.e., a sponge or brush) throughout the application time. To compare the effects of resin infiltration, twenty paired halves of specimens were treated with an infiltrant (ICON®).
Thicknesses of the removed surface layers and infiltrated areas were evaluated by confocal laser scanning microscope. The positive control and the 37% H3PO4 brush group failed to show significant differences in the removed thickness (p > 0.05); however, the mean percentage of the infiltrated area was higher in the 37% H3PO4 brush group (84.13 ± 7.58%) than the positive control (63.51 ± 7.62%, p < 0.001). Scanning electron microscope observations indicate higher pore volumes for the 37% H3PO4 brush group than for the positive control.
Application of 37% H3PO4 with a brush for 30 seconds increased the pore volume of WSL surface layers and the percentage of infiltrated areas in comparison to the use of 15% HCl for 120 seconds.
PMCID: PMC4130915  PMID: 25133134
White spot lesions (WSLs); Resin infiltration; Surface layer; 37% Phosphoric acid; 15% Hydrochloric acid
3.  Prophylactic Effect of Probiotics on the Development of Experimental Autoimmune Myasthenia Gravis 
PLoS ONE  2012;7(12):e52119.
Probiotics are live bacteria that confer health benefits to the host physiology. Although protective role of probiotics have been reported in diverse diseases, no information is available whether probiotics can modulate neuromuscular immune disorders. We have recently demonstrated that IRT5 probiotics, a mixture of 5 probiotics, could suppress diverse experimental disorders in mice model. In this study we further investigated whether IRT5 probiotics could modulate the progression of experimental autoimmune myasthenia gravis (EAMG). Myasthenia gravis (MG) is a T cell dependent antibody mediated autoimmune disorder in which acetylcholine receptor (AChR) at the neuromuscular junction is the major auto-antigen. Oral administration of IRT5 probiotics significantly reduced clinical symptoms of EAMG such as weight loss, body trembling and grip strength. Prophylactic effect of IRT5 probiotics on EMAG is mediated by down-regulation of effector function of AChR-reactive T cells and B cells. Administration of IRT5 probiotics decreased AChR-reactive lymphocyte proliferation, anti-AChR reactive IgG levels and inflammatory cytokine levels such as IFN-γ, TNF-α, IL-6 and IL-17. Down-regulation of inflammatory mediators in AChR-reactive lymphocytes by IRT5 probiotics is mediated by the generation of regulatory dendritic cells (rDCs) that express increased levels of IL-10, TGF-β, arginase 1 and aldh1a2. Furthermore, DCs isolated from IRT5 probiotics-fed group effectively converted CD4+ T cells into CD4+Foxp3+ regulatory T cells compared with control DCs. Our data suggest that IRT5 probiotics could be applicable to modulate antibody mediated autoimmune diseases including myasthenia gravis.
PMCID: PMC3527378  PMID: 23284891
4.  Immunomodulatory effect of water soluble extract separated from mycelium of Phellinus linteus on experimental atopic dermatitis 
Complementary and alternative medicine (CAM) is becoming a popular treatment for modulating diverse immune disorders. Phellinus linteus (P. linteus) as one of the CAMs has been used to modulate cancers, inflammation and allergic activities. However, little evidence has been shown about its underlying mechanism of action by which it exerts a beneficial role in dermatological disease in vivo. In this study, we examined the immunomodulatory effects of P. linteus on experimental atopic dermatitis (AD) and elucidated its action mechanism.
The immunomodulatory effect of total extract of P. linteus on IgE production by human myeloma U266B1 cells was measured by ELISA. To further identify the effective components, P. linteus was fractionated into methanol soluble, water soluble and boiling water soluble extracts. Each extract was treated to U266B1 cells and primary B cells to compare their inhibitory effects on IgE secretion. To test the in vivo efficacy, experimental atopic dermatitis (AD) was established by alternative treatment of DNCB and house dust mite extract into BALB/c mice. Water soluble extract of P. linteus (WA) or ceramide as a positive control were topically applied to ears of atopic mouse every day for 2 weeks and progression of the disease was estimated by the following criteria: (a) ear thickness, clinical score, (b) serum total IgE, IgG and mite specific IgE level by ELSIA, (c) histological examination of ear tissue by H&E staining and (d) cytokine profile of total ear cells and CD4+ T cells by real time PCR and ELSIA.
Treatment of total extracts of P. linteus to U266B1 inhibited IgE secretion. Among the diverse extracts of P. linteus, water soluble extract of P. linteus (WA) significantly reduced the IgE production in primary B cells and B cell line U266B1. Moreover, treatment of WA reduced AD symptoms such as ear swelling, erythema, and dryness and decreased recruitment of lymphocyte into the inflamed site. Interestingly WA treatment significantly reduced IgE level without affecting IgG levels and also down-regulated the levels of pathogenic cytokines (IL-4, IL-13, IL-12 and IFN-γ) and chemokines (CCL17 and CCL22) involved in AD development.
Our study indicates that protective effect of water soluble extract of P. linteus in atopic dermatitis is mediated by inhibiting IgE production and expression of AD associated pathogenic cytokines as well as chemokines, suggesting the beneficial effect of P. linteus to modulate allergic skin disease.
PMCID: PMC3479073  PMID: 22988890
5.  Abalone visceral extract inhibit tumor growth and metastasis by modulating Cox-2 levels and CD8+ T cell activity 
Abalone has long been used as a valuable food source in East Asian countries. Although the nutritional importance of abalone has been reported through in vitro and in vivo studies, there is little evidence about the potential anti-tumor effects of abalone visceral extract. The aim of the present study is to examine anti-tumor efficacy of abalone visceral extract and to elucidate its working mechanism.
In the present study, we used breast cancer model using BALB/c mouse-derived 4T1 mammary carcinoma and investigated the effect of abalone visceral extract on tumor development. Inhibitory effect against tumor metastasis was assessed by histopathology of lungs. Cox-2 productions by primary and secondary tumor were measured by real-time RT-PCR and immunoblotting (IB). Proliferation assay based on [3H]-thymidine incorporation and measurement of cytokines and effector molecules by RT-PCR were used to confirm tumor suppression efficacy of abalone visceral extract by modulating cytolytic CD8+ T cells. The cytotoxicity of CD8+ T cell was compared by JAM test.
Oral administration of abalone visceral extract reduced tumor growth (tumor volume and weight) and showed reduced metastasis as confirmed by decreased level of splenomegaly (spleen size and weight) and histological analysis of the lung metastasis (gross analysis and histological staining). Reduced expression of Cox-2 (mRNA and protein) from primary tumor and metastasized lung was also detected. In addition, treatment of abalone visceral extract increased anti-tumor activities of CD8+ T cells by increasing the proliferation capacity and their cytolytic activity.
Our results suggest that abalone visceral extract has anti-tumor effects by suppressing tumor growth and lung metastasis through decreasing Cox-2 expression level as well as promoting proliferation and cytolytic function of CD8+ T cells.
PMCID: PMC2972231  PMID: 20961430
6.  Cinnamon extract induces tumor cell death through inhibition of NFκB and AP1 
BMC Cancer  2010;10:392.
Cinnamomum cassia bark is the outer skin of an evergreen tall tree belonging to the family Lauraceae containing several active components such as essential oils (cinnamic aldehyde and cinnamyl aldehyde), tannin, mucus and carbohydrate. They have various biological functions including anti-oxidant, anti-microbial, anti-inflammation, anti-diabetic and anti-tumor activity. Previously, we have reported that anti-cancer effect of cinnamon extracts is associated with modulation of angiogenesis and effector function of CD8+ T cells. In this study, we further identified that anti-tumor effect of cinnamon extracts is also link with enhanced pro-apoptotic activity by inhibiting the activities NFκB and AP1 in mouse melanoma model.
Water soluble cinnamon extract was obtained and quality of cinnamon extract was evaluated by HPLC (High Performance Liquid Chromatography) analysis. In this study, we tested anti-tumor activity and elucidated action mechanism of cinnamon extract using various types of tumor cell lines including lymphoma, melanoma, cervix cancer and colorectal cancer in vitro and in vivo mouse melanoma model.
Cinnamon extract strongly inhibited tumor cell proliferation in vitro and induced active cell death of tumor cells by up-regulating pro-apoptotic molecules while inhibiting NFκB and AP1 activity and their target genes such as Bcl-2, BcL-xL and survivin. Oral administration of cinnamon extract in melanoma transplantation model significantly inhibited tumor growth with the same mechanism of action observed in vitro.
Our study suggests that anti-tumor effect of cinnamon extracts is directly linked with enhanced pro-apoptotic activity and inhibition of NFκB and AP1 activities and their target genes in vitro and in vivo mouse melanoma model. Hence, further elucidation of active components of cinnamon extract could lead to development of potent anti-tumor agent or complementary and alternative medicine for the treatment of diverse cancers.
PMCID: PMC2920880  PMID: 20653974

Results 1-6 (6)