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 [H(3)]-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)-1ß, 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-ß). In addition, rDCs generated by cinnamon extract inhibited APC-dependent T-cell proliferation, and converted CD4(+) T cells into IL-10(high) 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-1ß, 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.

Topical application of porcine placenta extract inhibits the progression of experimental contact hypersensitivity.

AIM OF STUDY: Placenta extract features as a composition of ointments used for skin beautification, dermatological diseases and skin dryness. However, little evidence has been cited about its underlying mechanisms of action by which it exerts a beneficial role in dermatological diseases in vivo. In this study, we intended to test the effect of topical application of porcine placenta extract in mouse model of contact hypersensitivity and elucidate its mechanism of action. MATERIALS AND METHODS: To test the in vitro effect of porcine placenta extract, RAW 264.7 cells were cocultured with porcine placenta extract and stimulated with LPS (1 µg/ml) and the expression of inflammatory mediator TNF-α was estimated by RT-PCR at the mRNA level and by intracellular staining at the protein level. To further test in vivo efficacy, porcine placenta extract was topically applied to the mice with experimental skin hypersensitivity. For in vivo studies placenta extract in gel form was topically applied to ear of DNCB-induced contact hypersensitivity mouse model everyday for 2 weeks and progression of the disease was estimated by following criteria: (a) ear thickness, (b) serum IgE level by ELISA, (c) histological examination of ear tissue by H&E staining and (d) cytokine profile of total cells and CD4(+) T cells by real time PCR. RESULTS: Topical application of porcine placenta extract on mouse ears with contact hypersensitivity decreased the severity and progression of the disease manifested by reducing ear swelling, inflammation and edema. Histological evaluation showed that placenta extract treatment reduced lymphocyte infiltration in the ear tissues. Protective effect of placenta extract is also associated with down-regulation of serum IgE level and inflammatory cytokine production (IL-1ß, IFN-γ, TNF-α, IL-4, IL-12 and IL-17) in total lymph node cells and CD4(+) T cells. CONCLUSIONS: Our data indicate that protective effect of porcine placenta extract in contact hypersensitivity is mediated by inhibition of the inflammatory responses and IgE production, suggesting a potential therapeutic application of porcine placenta extract to modulate skin inflammation.

Cinnamon extract induces tumor cell death through inhibition of NFkappaB and AP1.

BACKGROUND: 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 NFkappaB and AP1 in mouse melanoma model. METHODS: 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. RESULTS: 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 NFkappaB 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. CONCLUSION: Our study suggests that anti-tumor effect of cinnamon extracts is directly linked with enhanced pro-apoptotic activity and inhibition of NFkappaB 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.

Cinnamon extract suppresses tumor progression by modulating angiogenesis and the effector function of CD8+ T cells.

Cinnamon is one of the most widely used herbal medicines with diverse bioactive effects. However, little evidence has been reported about the potential anti-tumor effects of cinnamon. In vitro and in vivo system, cinnamon treatment strongly inhibited the expression of pro-angiogenic factors and master regulators of tumor progression not only in melanoma cell lines but also in experimental melanoma model. In addition, cinnamon treatment increased the anti-tumor activities of CD8(+) T cells by increasing the levels of cytolytic molecules and their cytotoxic activity. In conclusion, cinnamon extract has the potential to be an alternative medicine for tumor treatment.