• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.6
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• pp.902-907
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• 2012

The worldwide prevalence and severity of allergic diseases including atopic dermatitis and asthma 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 activities of the extract of Duchesnea chrysantha (DCE). DCE was prepared by extracting with 80% ethanol. In the present study, we investigate the effect of DCE on the production of tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$, IL-6, IL-8, and histamine in the human mast cell line (HMC-1 cells) and on the scratching behavior in hairless mice. Various concentrations of DCE were treated before the activation of HMC-1 cells with phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187. PMA plus A23187 significantly increased TNF-${\alpha}$, IL-$1{\beta}$, IL-6, and IL-8 production compared with media control. We also show that the increased cytokines such as TNF-${\alpha}$ IL-$1{\beta}$, IL-6, and IL-8 were significantly inhibited by DCE in a dose-dependent manner. Moreover, DCE inhibited the histamine release from HMC-1 cells stimulated by compound 48/80, which promotes histamine release. Futhermore, the administration of DCE reduced the scratching behavior induced by pruritogen (compound 48/80 or histamine) in hairless mice. These results suggest that DCE has a potential use as a medicinal plant for treatment against allergy-related disease.

• Journal of Life Science
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• v.21 no.3
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• pp.393-399
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• 2011

The mast cell is one of the major effector cells in inflammatory reactions and can be found in most tissues throughout the body. Activated mast cells can produce histamine, as well as a wide variety of other inflammatory mediators such as eicosanoids, proteoglycans, proteases, and several pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-${\alpha}$, and interleukins (IL-6), IL-8, IL-4, IL-13. In the present study, we isolated two bacterial strains (J80 and G147) from fermented soybean and Jeotgal, and investigated the inhibitory effects of their extracts which were prepared by several pretreatment methods (sonication for 20 min, heating at $100^{\circ}C$ for 30 min, autoclaving at $121^{\circ}C$ for 15 min) on the mast cell-mediated inflammatory response. The pretreated bacterial extracts had no cytotoxicity against Human Mast Cell (HMC-1). Among various pretreatments, the extracts treated at $100^{\circ}C$ showed highest inhibition of histamine release (J80, 28.46%; G147, 41.14%). The J80 and G147 extracts treated at $100^{\circ}C$ resulted in the inhibition of IL-6 secretion by 38.46% and 56.45%, respectively. The J80 extract treated at $100^{\circ}C$ resulted in the inhibition of TNF-${\alpha}$ secretion by 66.67%, but G147 extract showed the highest inhibition effect by 41.1% when treated with sonication. These results suggest that bacterial extracts treated at $100^{\circ}C$ have a higher level of anti-inflammatory effects than other treatments such as sonication or autoclaving.

• Biomolecules & Therapeutics
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• v.20 no.1
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• pp.43-49
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• 2012

Stimulation of mast cells through the high affinity IgE receptor (Fc${\varepsilon}$RI) induces degranulation, lipid mediator release, and cytokine secretion leading to allergic reactions. Although various signaling pathways have been characterized to be involved in the Fc${\varepsilon}$RI-mediated responses, little is known about the precious mechanism for the expression of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) in mast cells. Here, we report that rapamycin, a specific inhibitor of mammalian target of rapamycin (mTOR), reduces the expression of TNF-${\alpha}$ in rat basophilic leukemia (RBL-2H3) cells. IgE or specific antigen stimulation of RBL-2H3 cells increases the expression of TNF-${\alpha}$ and activates various signaling molecules including S6K1, Akt and p38 MAPK. Rapamycin specifically inhibits antigeninduced TNF-${\alpha}$ mRNA level, while other kinase inhibitors have no effect on TNF-${\alpha}$ mRNA level. These data indicate that mTOR signaling pathway is the main regulation mechanism for antigen-induced TNF-${\alpha}$ expression. TNF-${\alpha}$ mRNA stability analysis using reporter construct containing TNF-${\alpha}$ adenylate/uridylate-rich elements (AREs) shows that rapamycin destabilizes TNF-${\alpha}$ mRNA via regulating the AU-rich element of TNF-${\alpha}$ mRNA. The antigen-induced activation of S6K1 is inhibited by specific kinase inhibitors including mTOR, PI3K, PKC and $Ca^{2+}$chelator inhibitor, while TNF-${\alpha}$ mRNA level is reduced only by rapamycin treatment. These data suggest that the effects of rapamycin on the expression of TNF-${\alpha}$ mRNA are not mediated by S6K1 but regulated by mTOR. Taken together, our results reveal that mTOR signaling pathway is a novel regulation mechanism for antigen-induced TNF-${\alpha}$ expression in RBL-2H3 cells.

• Journal of Nutrition and Health
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• v.51 no.3
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• pp.208-214
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• 2018

Purpose: Platycodon grandiflorum (a domestic diploid variety, DV-PG) has been used as a food and component of various traditional oriental medicines. Although DV-PG is known to have an anti-allergic effect, little is known about the beneficial health effects of the tetraploid 'Etteum' variety in the Platycodon grandiflorum (TV-PG), which is a recently developed variety. In this study, we investigated the effect of TV-PG on the rat basophilic leukemia mast cell (RBL-2H3)-mediated allergic response. Methods: To examine the effects of TV-PG on the allergic response, RBL-2H3 cells were sensitized with dinitropheny (DNP)-immunoglobin E, treated with various concentrations of TV-PG, and challenged with DNP-human serum albumin. We estimated cell granulation by measuring the release of ${\beta}$-hexosaminidase and production of inflammatory mediators by ELISA. Results: TV-PG had no effect on the proliferation or cytotoxicity of RBL-2H3 cells within the concentration range of 0 to $200{\mu}g/mL$. TV-PG inhibited degranulation of RBL-2H3 cells by antigen stimulation in a dose-dependent manner. TV-PG also suppressed the production of inflammatory cytokines and mediators such as interleukin-4, tumor necrosis $factor-{\alpha}$, prostagladin E2, and leukotriene B4 in RBL-2H3 cells by antigen stimulation. Conclusion: These results indicate that TV-PG exhibits anti-allergic activity via inhibition of degranulation as well as suppression of inflammatory mediators and cytokine release. These findings suggest that TV-PG may have potential as a preventive and therapeutic agent for the treatment of various allergic diseases.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2018.10a
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• pp.128-128
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• 2018

Nypa fruticans wurmb (NF) has been used as traditional medicinal food in Asian countries. Especially, NF has been used for conventional medicine to treat inflammatory periodontal diseases. Previous studies have been shown that NF has large amount of useful constituents such as phenolic acids, polyphenols and flavonoids. Also, NF is known as having medicinal effects such as anti-oxidant, anti-inflammatory and cholesterol-lowering effects. NF has recently been attracted to use complementary medicinal food on inflammatory diseases in Korea. However, there are no obvious effects in inflammatory and metabolic diseases also mechanisms has been studied yet. The purpose of this study was to investigate the anti-inflammatory effects of NF and steamed-NF (SNF), which recently has been used as health food, using Human keratinocyte cell line (HaCaT) and Human mast cell line (HMC-1). The cytotoxicities of NF and SNF were measured by using MTT assays in HaCaT cells and HMC-1 cell. To evaluate anti-inflammatory effects of NF and SNF, HaCaT cells were stimulated with tumor necrosis factor $(TNF)-{\alpha}$ and Interferon $(IFN)-{\gamma}$. Also, HMC-1 cells were stimulated with phorbol-12-myristate-13-acetate (PMA) and A23187 calcium ionophore (A23187) to induce allergic inflammation. Inflammatory cytokine were measured by enzyme-linked immunosorbent assay (ELISA). In this result, the extract of NF and SNF (0.01 - 1mg/ml) did not show cytotoxicity in HaCaT cells and HMC-1 cells. In addition, the NF and SNF suppressed the production of interleukin (IL)-6 and IL-8 in HaCaT cells at highest concentration. Furthermore, the treatment of SNF significantly inhibited the secretion level of IL-8 in PMA plus A23187-stimulated HMC-1 cells compared with NF treatment group. These results suggest that the extract of NF and SNF may serve as a potential therapy for skin inflammatory diseases.

• CELLMED
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• v.3 no.2
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• pp.18.1-18.7
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• 2013

Inflammation in rheumatoid arthritis is characterized by immune cell infiltration and cytokine secretion. In particular, mast cells and their cytokines play an important role in the pathogenesis of rheumatoid arthritis. Korean medicine, BaekJeol-Tang (BT) was designed by traditional Korean medicine theory. We already reported therapeutic effect of BT in rheumatoid arthritis. Here, we report the specific underlying mechanism of BT in activated human mast cells, HMC-1 cells. In addition, we report for the first time that BT significantly inhibited the production and mRNA expression of proinflammatory cytokines including thymic stromal lymphopoietin, interleukin (IL)-$1{\beta}$, IL-6, IL-8, and tumor necrosis factor-${\alpha}$ in activated HMC-1 cells. BT also decreased the activation of mitogen-activated protein kinases, nuclear factor-${\kappa}B$, and caspapase-1. Taken together, these results indicate that BT has potential as a regulator of inflammatory reactions for the treatment of arthritis such as osteoarthritis and rheumatoid arthritis.

• Journal of Chitin and Chitosan
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• v.23 no.4
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• pp.277-284
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• 2018

In this study, we investigated the anti-allergic effect of the ethyl acetate fraction of Ecklonia cava (EC-EtoAc) on the immunoglobulin E (IgE)/bovine serum albumin (BSA)-mediated activation of bone marrow-derived cultured mast cells (BMCMCs). We revealed that the $62.5{\mu}g/ml$ of EC-fractions ($EC-CHCl_3$, EC-Hexane and EC-EtoAc) inhibited IgE/BSA-activated ${\beta}$-hexosaminidase release from BMCMCs without cytotoxicity. Especially, EC-EtoAc showed the higher ${\beta}$-hexosaminidase release than the others. Also, EC-EtoAc reduced the expression levels of cytokines such as interleukin (IL)-$1{\beta}$, IL-4, IL-5, IL-6, IL-10, IL-13, interferon (IFN)-${\gamma}$ and tumor necrosis factor (TNF)-${\alpha}$ and a chemokine, thymus- and activation-regulated chemokine (TARC), compared to the only IgE/BSA-treated BMCMCs. Furthermore, EC-EtoAc significantly prevented the binding of IgE to Fc epsilon receptor $(Fc{\varepsilon}R)I$ and reduced the $Fc{\varepsilon}RI$ expression on the sensitized BMCMCs. Taken together, these results suggest that E. cava may be the natural agent with beneficial potentials for the treatment of type I allergic diseases induced by mast cell activation.

• Microbiology and Biotechnology Letters
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• v.33 no.4
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• pp.260-266
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• 2005

IgE-dependent histamine releasing factor (HRF), previously known as P23/P21 or translationally controlled tumor protein (TCTP), induces the degranulation of histamine in mast cell and basophil. Yeast two hybrid results showed that HRF interacts with the alpha subunit of Na, K-ATPase, suggesting that HRF is a regulator for governing the activity of Na, K-ATPase. In this study, we examined the interaction of HRF and Wa,K-ATPase after treatments of various PKC isotype inhibitors. Membrane fractionation, pull-down assay and immunoprecipitation results showed that PKC $\alpha,\;PKC\;\beta,\;\delta$ subunits are involved in the phosphorylation of HRF. However, these results did not correlate with the results of histamine release assay since histamine release assay results suggested that some PKC isotype inhibitors induced the histamine release in RBL-2H3 cell.

• The Journal of Pediatrics of Korean Medicine
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• v.22 no.1
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• pp.103-111
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• 2008

Objectives Seunggal-tang is one of the prescriptions of oriental herbal medicine, which has been applied to several allergic diseases such as atopic dermatitis. This study was planned to compare differences of anti-allergic effects based on different form of Seunggal-tang by manufacturing differently. Methods Two types herb medicine products were used; aqueous extract (SG-T, Seunggal-Tang) and powder (SG-S, Seunggal-San) which were made from the same mixed formula of Seunggal-tang. To investigate in vitro anti-allergic activities, rat basophilic leukemia (RBL-2H3) cells were treated with SG-T and SG-S for 1 hour, and then stimulated with the phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187. We examined the release of beta-hexosaminidase, as a marker of degranulation, and the releases of tumor necrosis factor (TNF)-alpha and interleukin (IL)-4, as proinflammatory cytokines. Results SG-T and SG-S didn't have effects on cell viabilities in concentrations under 2㎎/㎖. In additionto that, SG-T more inhibited releasing ${\beta}$-hexosaminidase, TNF-${\alpha}$ and IL-4 than SG-S. Conclusions These results indicate that SG-T is more effective against mast cell-mediated allergic reactions than SG-S.

• Nutrition Research and Practice
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• v.17 no.5
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• pp.855-869
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• 2023

BACKGROUND/OBJECTIVES: Atopic dermatitis (AD) is a chronic disease with an increasing incidence globally; therefore, there is a growing demand for natural compounds effective in treating dermatitis. In this study, the protective effects of Lycium barbarum leaves with and without chlorophyll (LLE and LLE[Ch-]) on AD were investigated in animal models of AD and HaCaT cells. Further, we investigated whether LLE and LLE(Ch-) show any differences in physiological activity. MATERIALS/METHODS: AD was induced by 2,4-dinitrochlorobenzene (DNCB) for three weeks, while NC/Nga mice were fed LLE or LLE(Ch-) extracts for 7 weeks. Serum immunoglobulin E (IgE) and cytokine (tumor necrosis factor [TNF]-α, interleukin [IL]-6, and IL-4) concentrations and the degree of DNA fragmentation in lymphocytes were examined. A histopathological examination (haematoxylin & eosin staining and blue spots of toluidine) of the dorsal skin of mice was performed. To elucidate the mechanism of action, the expression of the thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) were measured in HaCaT cells. RESULTS: Serum IgE and cytokines (TNF-α and IL-6) levels as well as DNA fragmentation of lymphocytes were significantly decreased in AD-induced mice treated with LLE or LLE(Ch-) compared to those of the control group. The epidermal thickness of the dorsal skin and mast cell infiltration in the LLE group significantly reduced compared to that in the control group. The LLE extracts showed no cytotoxicity up to 1,000 ㎍/mL in HaCaT cells. LLE or LLE(Ch-)-treated group showed a reduction of TARC and MDC in TNF-α-and IFN-γ-stimulated HaCaT cells. CONCLUSIONS: These results suggest that LLE potentially improves inflammation by reducing the expression of chemokines that inhibit T helper 2 cell migration. LLE(Ch-) showed similar effects to LLE on blood levels of IgE, TNF-α and IL-6 and protein expression in HaCat cells, but the ultimate effect of skin improvement was not statistically significant. Therefore, both LLE and LLE(Ch-) can be used as functional materials to alleviate AD, but LLE(Ch-) appears to require more research to improve inflammation.