• Advances in Traditional Medicine
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• v.8 no.4
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• pp.440-447
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• 2008

This study investigated the role of Panax ginseng (PG) on the phorbol myristate acetate (PMA) + calcium ionophore A23187-induced hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) activation, phosphorylation of the extracellular signal-regulated kinase (ERK), and inflammatory cytokine production from the human mast cell line, HMC-1. HIF-$1{\alpha}$ and phosphorylation of ERK were observed by Western blotting. The inflammatory cytokine production was determined by enzyme-linked immunosorbent assay. PG inhibited the PMA+A23187-induced HIF-$1{\alpha}$ expression and the subsequent production of vascular endothelial growth factor. In addition, PG suppressed PMA + A23187-induced phosphorylation of ERK. We also show that the increased cytokines interleukin (IL)-$1{\beta}$, IL-6, and tumour necrosis factor-${\alpha}$ level was significantly inhibited by treatment of PG. In the present study, we report for the first time that PG is an inhibitor of HIF-$1{\alpha}$ and cytokines on the mast cell-mediated inflammatory responses.

• The Journal of Pediatrics of Korean Medicine
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• v.18 no.2
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• pp.31-48
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• 2004

Objective : KagamJwagwiEum(KJE) has been used for the purpose of prevention and treatment of bronchial asthma and allergic asthma in Korea. To investigate the biological effect of KJE, the author examined cytotoxicity and inflammatory cytokines secretion with human leukemic mast cell line, HMC-1. Methods: HMC-1 was stimulated with phorbol 12-myristate 13-acetate(PMA) and calcium ionophore A23187. KJE by itself had no effect on viability of HMC-l. The effects of KJE on the secretion of tumor necrosis $factor-alpha(TNF-{\alpha})$, interleukin(IL)-6 and IL-8 from HMC-1 were evaluated with enzyme-linked immunosorbent assay. Results : KJE inhibited PMA plus A23187-induced $TNF-{\alpha}$ and IL-6 secretion. But KJE had no effect IL-8 secretion: KJE had immunoregulatory effects on cytokines, increased secretion of NO and $TNF-{\alpha}$ but did not effect IL-12 secretion when the cells were primed and trigged with $IFN-{\gamma}$ in the peritoneal macrophages of C57BL/6 mice. Conclusions : Taken together, these results suggest that KJE inhibit the production of inflammatory cytokines in HMC-1 cells and activate macrophages.

• Natural Product Sciences
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• v.12 no.3
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• pp.144-149
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• 2006

The immediate-type allergic reaction (anaphylaxis) is involved in many allergic diseases such as asthma, allergic rhinitis, and sinusitis. The discovery of drugs for the treatment of immediate-type allergic diseases is a very important subject in human health. In this study, we investigated the effect of Rubus coreanus Miq.(Rosaceae) unripe fruits (RCF) on mast cell-mediated allergic reaction and inflammatory cytokine secretion. RCF inhibited compound 48/80-induced systemic reactions in mice. RCF attenuated immunoglobulin (Ig) E-mediated local allergic reactions. In addition, RCF dependently reduced histamine release from rat peritoneal mast cells local allergic reactions. In addition, RCF dependently reduced histamine release from rat peritoneal mast cells activated by compound 48/80 or IgE. Furthermore, RCF decreased the phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated tumor necrosis factor $(TNF)-{\alpha}$ and interleukin (IL)-6 secretion in human mast cells. Our findings provide evidence that RCF inhibits mast cell-derived immediate-type allergic reactions.

• Advances in Traditional Medicine
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• v.6 no.3
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• pp.237-244
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• 2006

Samultang has been believed for prevention and remedy various blood diseases such as menstrual irregularity, anemia, and metrorrhagia. However, the mechanism that accounts for anti-inflammatory effects of the Samultang is still not fully understood. This study was designed to evaluate whether and how the Samultang could modulate the production of pro-inflammatory cytokines in phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187 treated-human mast cell line, HMC-1. Samultang inhibited the production of tumor necrosis factor $(TNF)-\alpha$, interleukin (IL)-6, granulocyte macrophage colony stimulating factor (GM-CSF), and vascular endothelial growth factor (VEGF) in HMC-1. Maximal inhibition rate of $TNF-\alpha$, IL-6, GM-CSF, and VEGF by 0.1 mg/ml Samultang was about $70.73{\pm}3.0%,\;51.49{\pm}4.14%,\;54.03{\pm}2.09%$, and $47.95{\pm}7.86%$, respectively. Samultang partially blocked PMA plus A23187-induced cyclooxygenase (COX)-2 expression. In addition, Samultang inhibited activation of nuclear factor (NF)-kB, and extracellular signal-regulated kinase (ERK) activation. These results suggest that anti-inflammatory effect of Samulatng may be mediated by the suppression of cytokine production and COX-2 activation via down-regulation of NF-kB and ERK activation.

• Korean Journal of Pharmacognosy
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• v.44 no.1
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• pp.60-69
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• 2013

The worldwide prevalence and severity of allergic diseases including atopic and contact dermatitis has increased dramatically over the past decade, especially in developed countries. Mast cells are important effector cells in allergic reactions. The purpose of this study was undertaken to investigate the anti-allergic and anti-pruritic effects of Diospyros lotus leaf extract (DLE). DLE was prepared by extracting with distilled water. In the present study, we investigated the effect of DLE on the production of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-$1{\beta}$ (IL-$1{\alpha}$) and histamine in rat peritoneal mast cells (RPMCs), and on the skin lesion, leukocyte infiltration and scratching behavior in mice. Phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187 significantly increased TNF-${\alpha}$ and IL-$1{\beta}$ production compared with media control. However, TNF-${\alpha}$ and IL-6 production increased by PMA plus A23187 treatment were significantly inhibited by DLE in a dose-dependent manner. DLE also inhibited the histamine release from RPMCs stimulated by compound 48/80, which promotes histamine release. Moreover, DLE administration had an inhibitory effects on the scratching behavior induced by pruritogen (compound 48/80, histamine) in ICR mice. Furthermore, DLE inhibited the skin lesions, inflammatory and mast cells in hairless mice sensitized by 2,4-dinitrofluorobenzene (DNFB). DLE administration reduced the IL-4 and IgE production induced by DNFB sensitization in hairless mice. These results suggest that DLE has a potential use as a herb medicine for treatment against allergy and pruritus-related disease.

• Biomolecules & Therapeutics
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• v.21 no.6
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• pp.435-441
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• 2013

Emodin, a naturally occurring anthraquinone derivative isolated from Polygoni cuspidati radix, has several beneficial pharmacologic effects, which include anti-cancer, anti-diabetic, and anti-inflammatory activities. In this study, the authors examined the effect of emodin on the production of proinflammatory cytokines, such as, tumor necrosis factor (TNF)-${\alpha}$ and interleukin (IL)-6, in mouse bone marrow-derived mast cells (BMMCs) stimulated with phorbol 12-myristate 13-acetate (PMA) plus the calcium ionophore A23187. To investigate the mechanism responsible for the regulation of pro-inflammatory cytokine production by emodin, the authors assessed its effects on the activations of transcriptional factor nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and mitogen-activated protein kinases (MAPKs). Emodin attenuated the nuclear translocation of (NF)-${\kappa}B$ p65 and its DNA-binding activity by reducing the phosphorylation and degradation of $I{\kappa}B{\alpha}$ and the phosphorylation of $I{\kappa}B$ kinase B (IKK). Furthermore, emodin dose-dependently attenuated the phosphorylations of MAPKs, such as, extracellular signal-regulated kinase 1/2 (ERK1/2), p38 MAP kinase, and the stress-activated protein kinases (SAPK)/c-Jun-N-terminal kinase (JNK). Taken together, the findings of this study suggest that the anti-inflammatory effects of emodin on PMA plus A23187-stimulated BMMCs are mediated via the inhibition of NF-${\kappa}B$ activation and of the MAPK pathway.

• The Journal of Korean Medicine
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• v.23 no.2
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• pp.19-27
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• 2002

Objective : This study was designed to investigate the effect of Hyeolbuchukeo-tang (HCT) on NO production and the molecular mechanism of NO production modulated by HCT in the primary VSMC (vascular smooth muscle cells). Method : Primary VSMC was established from aorta and cultured VSMC used in this study. NO production of VSMC was assayed by Griess reagent and the expression of iNOS gene was assayed by Western, RT-PCR. Result : $TNF-{\gamma}$ induced NO production, but $IFN-{\gamma}$ or HCT alone did not induce NO production in cultured VSMC. However, $IFN-{\gamma}$ or HCT potentiated NO production in $TNF-{\gamma}-treated$ VSMC in a time- and dose-dependent manner. $TNF-{\gamma}$ induced the iNOS gene expression corresponding to NO production in $TNF-{\gamma}-treated$ VSMC. HCT potentiated NO production in $TNF-{\gamma}-treated$ VSMC by about 20%, but HCT did not increase the level of iNOS mRNA in $TNF-{\gamma}-treated$ VSMC. HCT slightly increased the level of iNOS protein in $TNF-{\gamma}-treated$ VSMC. Calcium ionophore A23187 decreased NO production in $TNF-{\gamma}-treated$ VSMC, but HCT attenuated the effect of A23187. Conclusion : As NO is deeply involved in the development of arteriosclerosis and dilation of blood vessels, drugs or chemicals modulating NO production in VSMC could be used for preventing and treating arteriosclerosis. Considering the effect of HCT on the modulation of NO production in VSMC, MCT has a potential capacity for preventing and treating diseases of the circulation system including arteriosclerosis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.3
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• pp.438-444
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• 2011

Dojuk-San is known to be effective for treating a urinary diseases and stomatitis. However, its effects on the bone marrow-derived mast cell(BMMC) mediated allergy and inflammation mechanism remain unknown. In this study, the biological effects of Dojuk-San ethanol extract(DJS) were evaluated while focusing on its effects on the allergic mediator in phorbol 12-myristate 13-acetate(PMA) plus calcium ionophore A23187(A23187)-stimulated BMMCs. An investigation was also conducted to determine its effects on the production of several allergic mediators including interleukin-6(IL-6), prostaglandin D2($PGD_2$), leukotrieneC4(LTC4) and ${\beta}$-Hexosaminidase(${\beta}$-Hex). The results revealed that DJS inhibited the PMA plus A23187 induced production of IL-6, PGD2, LTC4 and ${\beta}$-Hex. Taken together, these findings indicate that DJS has the potential using in the treatment of allergy.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.3
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• pp.660-665
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• 2008

In the present study, we investigated the anti-allergic effect of the water extract of Bopyeoyangyeong-jun(BYJ). To investigate the biological effect of BYJ, We examined cytotoxicity and inflammatory cytokine secretion with RBL-2H3. We examined Cell Viability, ${\beta}$-hexosaminidase, tumor necrosis factor-alpha(TNF-${\alpha}$), interleukin(IL)-4 secretion from RBL-2H3 cell after pre- treatment with Bopyeoyangyeong-jun of 1 mg/ml, 2 mg/ml. RBL-2H3 cell was stimulated with phorbol 12-myristate 13-acetate(PMA) and calcium ionophore A23187. BYJ by itself had no effect on viability of RBL-2H3 cell. We observed that Bopyeoyangyeong-jun reduced ${\beta}$-hexosaminidase, TNF-${\alpha}$, IL-4 secretion in RBL-2H3 cell. Taken together, these results indicate that Bopyeoyangyeong-jun has anti-histamic effect and controls TNF-${\alpha}$, IL-4 secretion on allergic reaction.

• Development and Reproduction
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• v.3 no.1
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• pp.87-93
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• 1999

The possible role of Na$^{+}$/H$^{+}$ antiporter in both the capacitation and the acrosome reaction (AR) was examined in mouse epididymal spermatozoa. Spontaneous acrosome reaction was inhibited by dimethyl amiloride (DMA), a specific inhibitor of Na$^{+}$/H$^{+}$ antiporter, with dose dependent manner. Follicular fluid- or A23l 87-induced acrosome reaction was not inhibited by DMA. It suggests that change in pH$_{i}$ by monovalent cation transport through the Na$^{+}$/H$^{+}$ antiporter is possibly engaged in the capacitation and that agonist- as well as A23l87-induced AR in capacitated sperm might be independent from the Na$^{+}$/H$^{+}$ antiporter. Conclusively, changes in pH$_{i}$ through the Na$^{+}$/H$^{+}$ antiporter might be important for sperm capacitation and it virtually occurs upstream of the $Ca^{2+}$ influx which precedes the acrosome reaction in mouse epididymal spermatozoa.pididymal spermatozoa.