[논문]Syk kinase 억제를 통한 관중의 항앨러지 효과

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Syk kinase 억제를 통한 관중의 항앨러지 효과
Crassirhizomae rhizoma Exhibits Anti-Allergic Activity through Inhibition of Syk Kinase in Mast Cells 원문보기

韓國藥用作物學會誌 = Korean journal of medicinal crop science, v.16 no.1, 2008년, pp.27 - 32

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This study aimed to investigate the anti-allergic activity and the mechanism of action of Crassirhizomae rhizoma (CR). The extract of CR exhibited potent inhibitory activity in mast cells; its $IC_{50}$ values were $31.2{\pm}1.5{\mu}g/m{\ell}$ for rat basophile leukemia (RBL)-2H3 mast cells and $51.5{\pm}2.1{\mu}g/m{\ell}$ for bone marrow-derived mast cells by antigen stimulation. It also suppressed the expression of TNF-${\alpha}$ and IL-4 mRNAs in RBL-2H3 cells. In an in-vivo animal allergy model, it inhibited a local allergic reaction, passive cutaneous anaphylaxis (PCA), in a dose-dependent manner. With regard to the mechanism of action, CR inhibited the activating phosphorylation of Syk kinase, a key signaling protein for the activation of mast cells. Taken together, these results strongly suggested that the anti-allergic activity of CR is mediated through the inhibition of histamine release and allergic cytokine production by the inhibition of Syk in mast cells.

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문제 정의

However, the anti-allergic activity of CR extract has not yet been reported on. The aim of this study was to investigate the anti-allergic activity of the CR extract using an in vitro and in vivo local allergic mouse model.

제안 방법

CR (dose ranged from 100-1000 ㎎/㎏) was orally administrated 1 hr before the treatment of antigen. One hour after the challenge of antigen, the mouse was killed and the ear was removed for tne measurement of the amount of extravasated dye induced by antigen treatment Values are expressed as mean values from two independent experiments.
The cultures were incubated fdr 30 min with or without CR before stimulating with 25 ng/mℓ DNP-BSA for 10 min. The degranulation was evaluated by the measurement of the release of the granule marker p-hexosaminidase using a colorimetric assay, through which the release of p-nitrophenol from p-nitrophenyl-N-acetyl-p-D-glucosaminide was measured. The values were expressed as percentages of intracellular P-hexosaminidase released into the medium.
Several allergic animal models such as a compound 48/80-mediated anaphylactic animal model and IgE-mediated PCA model have been used for determining the in vivo effects of anti-allergic agents. This study used a mast cell-mediated PCA mouse model to confirm the in vitro inhibitory effect on degranulation in mast cells. As shown in Fig.
To determine the mechanism of action on degranulation and the expression of cytokines, whether or not CR suppressed various signaling molecules including Syk and LAT was tested. Syk kinase is well known as an important signaling protein tyrosine kinase for the activation of mast cells and LAT is a down stream adaptor molecule of Syk kinase for forming an early signaling complex.
Thus, intervention in the allergen-mediated activation of mast cells is a long-sought after goal in the treatment and management of allergic diseases (Kim, 2006). To screen some anti-allergic agent, this study used two kinds of mast cells, RBL-가13 cells and BMMCs. As shown in Fig.

대상 데이터

Dinitrophenol (DNP)-bovine serum albumin (BSA), DNP- specific monoclonal IgE, and Arabic gum were purchased from Sigma Chemical Co. (St. Louis, MO, USA). Antibodies were obtained from the following sources antibodies for the phosphorylated forms of Syk, ERK1/2, p38, and JNK from Upstate Biotechnology (Lake Placid, NY, USA); antibodies for Syk and Actin from Santa Cruz Biotechnology Inc.

데이터처리

Statistical analysis was performed using a one-way ANOVA and the Dunnett's test. All statistical calculations (*, p<0.05 and **, p< 0.01) were performed using the SigmaStat software (Systat Software, Inc.; Point Richmond, CA, USA).
more separate experiments. Statistical analysis was performed using a one-way ANOVA and the Dunnett's test. All statistical calculations (*, p<0.
The values were expressed as percentages of intracellular P-hexosaminidase released into the medium. The IC₅₀ values were calculated through nominear regression analysis using the GrshPad software (San Diego, CA, USA).

참고문헌 (19)

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원문보기 상세보기
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Syk kinase 억제를 통한 관중의 항앨러지 효과
Crassirhizomae rhizoma Exhibits Anti-Allergic Activity through Inhibition of Syk Kinase in Mast Cells 원문보기

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Syk kinase 억제를 통한 관중의 항앨러지 효과 Crassirhizomae rhizoma Exhibits Anti-Allergic Activity through Inhibition of Syk Kinase in Mast Cells 원문보기

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참고문헌 (19)

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Syk kinase 억제를 통한 관중의 항앨러지 효과
Crassirhizomae rhizoma Exhibits Anti-Allergic Activity through Inhibition of Syk Kinase in Mast Cells 원문보기

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