• The Korea Journal of Herbology
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• v.35 no.5
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• pp.13-21
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• 2020

Objective : The genus Glycyrrhiza has been used in food and traditional herbal medicine. Many experimental studies reported that Glycyrrhiza species possess several pharmacological properties. Glycyrrhiza new varieties WONGAM and SINWONGAM have been developed by Korea Rural Development Administration doing research for registration on Ministry of Food and Drug Safety. During the evaluations about pharmacological effect of Glycyrrhiza new varieties WONGAM and SINWONGAM, we focused the anti-allergic effect in this study. Methods : We investigated the anti-allergic effect of WONGAM and SINWONGAM compared with Glycyrrhiza uralensis Fischer and G. glabra L. using anti-dinitrophenyl-immunoglobulin E (IgE)/human serum albumin-stimulated RBL-2H3 cells, phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated HMC-1 cells and compound 48/80-induced anaphylaxis mice model. We analyzed the effect on the expression of various cytokines, and IgE from mast cells and the underlying molecular mechanisms of WONGAM and SINWONGAM in presented models. Results : WONGAM and SINWONGAM showed the inhibitory effect on the histamine release from rat peritoneal mast cells or human mast cells without cytotoxicity. WONGAM and SINWONGAM blocked anaphylactic shock and decreased the IgE production. Furthermore, WONGAM and SINWONGAM inhibited the productions of TNF-α and IL-6 in compound 48/80-induced anaphylaxis mice model. Conclusion : These results indicated that WONGAM and SINWONGAM would have protect effect on allergic responses through the inhibition of allergic mediators and pro-inflammatory cytokines. This study may facilitate the development on Glycyrrhiza new varieties for allergy.

• Journal of Periodontal and Implant Science
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• v.26 no.2
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• pp.376-395
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• 1996

The neuropeptide substance P(SP) has been recognized to modulate immune systems, with close proximity between peptidergic sensory nerve endings and immune cells. These include the macrophage and neutrophil activation, IL-2 production in T cell, augmentation of Ig synthesis, mast cell degranulation, $PGE_2$ and collagenase secretion in synoviocytes. In this study I examined SP-induced various biological activities such as antimicrobial action, cytokine production, and mast cell degranulation in the presence or absence of other inflammatory cell activators. Antimicrobial studies showed that undifferentiated HL-60 cells were not affected by SP. However, SP significantly enhanced antimicrobial action of TPA-treated or dbcAMP-treated HL-60 cells which had been differentiated into PMN or macrophage/monocyte. I could not find synergistic relationship between SP and LPS in parallel experiments of the above. SP did not induce IL-l production from murine macrophage cell line RAW264.7 whether costimulated with LPS or not. Mast cell degranulation was occured only when stimulated with high dose ($10^{-5}M$) of SP and the degree of this activation was slightly reduced by simultaneous application of $MIP-1{\alpha}$. In addition, CGRP which is known to be a common coexisting neuropeptide with SP within specific fibers did not augment the function of SP on mast cell degranulation. These results suggest that immunoregulatory activities of SP could be mediated through direct upregulation of various functions of immune cells and also upregulation of responsiveness of immune cells to other immune activators.

• The Journal of Internal Korean Medicine
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• v.30 no.1
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• pp.9-23
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• 2009

Objectives : Asthma is a chronic inflammatory disorder of the airways by many cells such as mast cells, Th2 lymphocytes and eosinophile. The present study was aimed to evaluate the effects of Salviae miltiorrhizae (SM) on T cell cytokine production, mast cells. and eosinophils, Methods : We screened 13 herbs to find compounds with potential to control Th cytokine production. using concanavalin A (con A)-activated splenocyte cultures. Con A-activated $IFN-\gamma$ and IL-4 levels in supernatants of splenocyte cultures. Bone marrow derived mast cells (BMMC) were incubated with SM and then the expressions of membrane proteins of BMMC were analyzed by fluorescence activated cell sorter (FACS). BALB/c mice sensitized to ovalbumin (OVA) were challenged with aerosolized OVA for 6 weeks. During the last weeks some mice were treated with SM. Then eosinophils in bronchoalveolar lavage fluid (BALf) were counted and pathologic changes of lung tissue were observed with hematoxylin-eosin stain. Results : SM increased $IFN-\gamma$ level on splenocyte culture significantly. but had no significant effects on expressions of ICAM-1, CD62L, integrin $a_4$. c-kit, IL-3 receptors. CD11a, or IgE receptors of BMMC. SM treatment significantly inhibited eosinophil infiltrates in BALf and peribronchial lung inflammation. Conculusions : The present data suggested that SM may have an effect on Th cytokine secretion and eosinophils associated with asthma responses. Therefore SM might be of therapeutic value in treating asthma.

• Journal of the korean academy of Pediatric Dentistry
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• v.26 no.2
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• pp.350-364
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• 1999

The distribution of mast cells and nerves were investigated in the submandibular and sublingual glands of postnatal rats, using morphometric, histochemical and immunohistochemical techniques. Mast cells were observed in the submandibular and sublingual glands of postnatal development. Number of mast cells gradually increased in both glands following development. At birth, mast cells were relatively fewer in submandibular gland than those in sublingual gland, and they were mainly distributed in parenchymal tissues. At $2{\sim}4$ weeks, most of the mast cells were observed in the connective tissues, surrounding neurovascular elements, but some mast cells were closely related with the acini of submandibular gland. PGP 9.5 immunoreactive nerve fibers were found in the submandibular and sublingual glands of all developmental age. The nerve fibers were showed in varicose shape, and mainly located in adjacent area of ducts and vascular components of both glands. The number of nerve fibers were increased rapidly until 8 weeks, but they were not increased any more until 24 weeks. Therefore, it is suggested that mast cells and nerve fibers related with each other, and that their interactions may play roles not only in maturation of secretory units but also growth and differentiation of the tubular structures of the rat submandibular and sublingual glands during postnatal development.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.254.2-254.2
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• 2002

Mast cells play an important role in inflammation by functioning as a source of histamine, tryptase, and proinflammatory cytokines. Lonicera Japonica (Caprifoliaceae. Lc) has been used to treat inflammation. We investigated whether the water extract of Lonicera Japonica(Lc) inhibit production of inflammatory mediators such as tryptase and tumor-necrosis factor (TNF)-${\alpha}$, and phosphorylation of extracellular signal-regulated kinase(ERK) in trypsin-stimulated HMC-1. (omitted)

• Journal of the korean academy of Pediatric Dentistry
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• v.28 no.1
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• pp.72-81
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• 2001

Dendroaspis natriuretic peptide (DNP), recently isolated from the venom of the green Mamba snake Dendroaspis angusticeps, is a 38-amino acid peptide containing a 17-amino acid disulfide ring structure similar to that of the natriuretic peptide family. The natriuretic peptide family was known to induce histamine release from human and rat mast cells, but there are no published data concerning the effects of DNP on histamine release from mast cells. The purpose of this study is to investigate whether DNP induces the histamine release from rat peritoneal mast cells (RMPCs) and to determine the mechanism of DNP-induced histamine release from RPMCs. After treatment of the various doses of DNP in RPMCs, the mast cell degranulation was observed with inverted microscopy and the histamine release was measured by radio-enzymatic assay. Calcium uptake and intracellular cyclic GMP level were measured by radioimmunoassays. DNP induced the mast cell degranulation. DNP released the histamine and increased the calcium uptake and the level of intracellular cyclic GMP of RPMCs, in a dose-dependent manner. The results indicate that DNP is capable of inducing histamine release from RPMCs by increasing of calcium uptake and intracellular cyclic GMP level.

• Journal of Ginseng Research
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• v.46 no.4
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• pp.550-560
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• 2022

Background: The effect of ginsenoside Rh2 (G-Rh2) on mast cell-mediated anaphylaxis remains unclear. Herein, we investigated the effects of G-Rh2 on OVA-induced asthmatic mice and on mast cell-mediated anaphylaxis. Methods: Asthma model was established for evaluating airway changes and ear allergy. RPMCs and RBL-2H3 were used for in vitro experiments. Calcium uptake, histamine release and degranulation were detected. ELISA and Western blot measured cytokine and protein levels, respectively. Results: G-Rh2 inhibited OVA-induced airway remodeling, the production of TNF-α, IL-4, IL-8, IL-1β and the degranulation of mast cells of asthmatic mice. G-Rh2 inhibited the activation of Syk and Lyn in lung tissue of OVA-induced asthmatic mice. G-Rh2 inhibited serum IgE production in OVA induced asthmatic mice. Furthermore, G-Rh2 reduced the ear allergy in IgE-sensitized mice. G-Rh2 decreased the ear thickness. In vitro experiments G-Rh2 significantly reduced calcium uptake and inhibited histamine release and degranulation in RPMCs. In addition, G-Rh2 reduced the production of IL-1β, TNF-α, IL-8, and IL-4 in IgE-sensitized RBL-2H3 cells. Interestingly, G-Rh2 was involved in the FcεRI pathway activation of mast cells and the transduction of the Lyn/Syk signaling pathway. G-Rh2 inhibited PI3K activity in a dose-dependent manner. By blocking the antigen-induced phosphorylation of Lyn, Syk, LAT, PLCγ2, PI3K ERK1/2 and Raf-1 expression, G-Rh2 inhibited the NF-κB, AKT-Nrf2, and p38MAPK-Nrf2 pathways. However, G-Rh2 up-regulated Keap-1 expression. Meanwhile, G-Rh2 reduced the levels of p-AKT, p38MAPK and Nrf2 in RBL-2H3 sensitized IgE cells and inhibited NF-κB signaling pathway activation by activating the AKT-Nrf2 and p38MAPK-Nrf2 pathways. Conclusion: G-Rh2 inhibits mast cell-induced allergic inflammation, which might be mediated by the AKT-Nrf2/NF-kB and p38MAPK-Nrf2/NF-κB signaling pathways.

• Bulletin of the Korean Chemical Society
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• v.28 no.10
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• pp.1725-1728
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• 2007

Mast cells are key effector cells in the early phase allergic inflammation and in diverse immunological and pathological processes. In order to understand the effect on reduction of the anti-dinitrophenyl (DNP) IgE antibody-induced β-hexosaminidase release in RBL-2H3 rat mast cells, a novel series of 4-senecioyloxymethyl- 6,7-dimethoxycoumarins (SMDC) was prepared by reacting 4-chloromethyl-6,7-dimethoxycoumarin with various carboxylic acids. Compounds 8-11 with cyclic moiety such as phenyl, thiophenyl, pyridinyl, and furanyl group were found to inhibit-hexosaminidase release more potently (5.98-9.62 μM) than compounds 3- 7 and 12 with acyclic moiety (19.32-76.78 μM). Furthermore, compounds 8 and 9 inhibited IgE-induced ear swelling and significantly reduced systemic passive cutaneous anaphylaxis reaction in mice.

• Natural Product Sciences
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• v.16 no.3
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• pp.185-191
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• 2010

Mast cell-mediated allergic disease is involved in many diseases such as anaphylaxis, asthma and atopic dermatitis. The discovery of drugs for the treatment of allergic disease is an important subject in human health. In the present study, the effect of water extract of Gleditsiae Spina (WGS) (Leguminosae), on compound 48/80-induced systemic allergic reaction, anti-DNP IgE antibody-induced local allergic reaction, and histamine release from human mast cell line (HMC-1) cells were studied. In addition, the effect of WGS on phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187 (A23187)-induced gene expression and secretion of pro-inflammatory cytokines were investigated using HMC-1 cells. WGS was anally administered to mice for high and fast absorption. WGS inhibited compound 48/80-induced systemic allergic reaction. WGS dose-dependently decreased the IgE-mediated passive cutaneous anaphylaxis. WGS reduced histamine release from HMC-1 cells. In addition, WGS decreased the gene expression and secretion of pro-inflammatory cytokines in PMA plus A23187-stimulated HMC-1 cells. These findings provide evidence that WGS could be a candidate as an antiallergic agent.

• Korean Journal of Plant Resources
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• v.28 no.3
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• pp.321-328
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• 2015

Alpiniae officinarum Rhizoma (the rhizome of Alpinia officinarum Hance, known as lesser galangal), a family of Zingiberaceae, has been used to reduce pain of infection and inflammatory diseases in Asian countries. The present study was focused to evaluate the inhibitory degranulation effect of Alpiniae officinarum Rhizoma extract in RBL-2H3 rat basophilic leukemia cells. Cell viability was measured by MTT assay. RBL-2H3 cells were stimulated by phorbol 12-myristate 13-acetate and calcium ionophore A23187. Mast cell degranulation was analyzed by measuring release of β-hexosaminidase in RBL-2H3 cell. Gene expression was measured by qRT-PCR and signaling molecules were detected by immunoblotting. The Alpiniae officinarum Rhizoma extract suppressed β-hexosaminidase release in dose-dependent manner and inhibited cycloxygenase-2 and tumor necrosis factor-α gene expression. Furthermore, it was found that Alpiniae officinarum Rhizoma extract reduced mitogen-activated protein kinases, especially phosphorylated p38, at 0.75 ㎎/㎖ of Alpiniae officinarum Rhizoma extract concentrations. These data show that Alpiniae officinarum Rhizoma extract has immunosuppressive effect in mast cell induced allergic inflammation.