• Journal of Pharmacopuncture
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• v.15 no.4
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• pp.32-41
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• 2012

Objectives: Rehmannia glutinosa pharmacopuncture solution (RGPS) was investigated to determine both its anti-allergic inflammatory effects on mast cells and its detailed mechanism of actions. Methods: We investigated whether RGPS suppress cytokines, enzymes, $Fc{\varepsilon}RI$ expression and $Fc{\varepsilon}RI$-mediated signaling in RBL-2H3 cells stimulated with anti-DNP IgE/DNP-HSA. The suppressive effects of RGPS on the levels of cytokines such as IL-$1{\beta}$, IL-6 and GM-CSF were measured using emzyme-linked immunospecific assay (ELISA). The mRNA expression levels of cytokines, enzymes (HDC2, COX-1, COX-2 and 5LO) and $Fc{\varepsilon}RI$ ${\alpha}{\beta}{\gamma}$ subunits were measured using reverse transcription polymerase chain reaction (RT-PCR) method. The activation of $Fc{\varepsilon}RI$-mediated signaling was examined using Western blot analyses. Results: RGPS suppressed production of proinflammatory cytokines (IL-$1{\beta}$, IL-6, and GM-CSF) in stimulated RBL-2H3 cells significantly (p < 0.05). RGPS also suppressed mRNA expression of inflammatory enzymes (HDC2, COX-1, COX-2, 5LO). In addition, mRNA expression levels of $Fc{\varepsilon}RI{\alpha}$, $Fc{\varepsilon}RI{\beta}$and $Fc{\varepsilon}RI{\gamma}$ were lowered by treatment with RGPS. Finally, RGPS prevented phosphrylation of Lyn, Syk, LAT, Gab2, PLC ${\gamma}1/2$, PI3K, Akt, cPLA2 and $I{\kappa}B{\alpha}$. Conclusions: RGPS effectively suppresses mast cell activations such as degranulation and inflammatory response via down-regulation of the $Fc{\varepsilon}RI$-mediated signaling pathways in IgE/Ag-stimulated mast cells.

• International Journal of Molecular Medicine
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• v.43 no.5
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• pp.2252-2258
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• 2019

Thymic stromal lymphopoietin (TSLP) plays an important role in allergic disorders, including atopic dermatitis and asthma. Ursolic acid (UA) has various pharmacological properties, such as antioxidant, anti-inflammatory and anticancer. However, the effect of UA on TSLP regulation has not been fully elucidated. The aim of the present study was to analyze how UA regulates the production of TSLP in the human mast cell line HMC-1. Enzyme-linked immunosorbent assay, quantitative polymerase chain reaction analysis, western blotting, caspase-1 assay and fluorescent measurements of intracellular calcium levels were conducted to analyze the regulatory effects of UA. The results revealed that UA inhibited TSLP production and mRNA expression. In addition, UA reduced the activation of nuclear factor-κB and degradation of IκBα. Caspase-1 activity was increased by exposure to phorbol myristate acetate plus calcium ionophore, whereas it was reduced by UA. Finally, UA treatment prevented an increase in intracellular calcium levels. These results indicated that UA may be a useful agent for the treatment and/or prevention of atopic and inflammatory diseases, and its effects are likely mediated by TSLP downregulation.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.19 no.3 s.31
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• pp.13-21
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• 2006

Object : We investigated the effect of Gamiokyaek-tang (GOYT) on immediate type hypersensitivity. Methods : We investigated anti-dinitrophenyl (DNP) IgE-mediated passive cutaneous anaphylaxis and acetic acid-induced vascular permeability in rodents. Also perfonned MTT assay and b-hexosaminidase activity is measured in RBL-2H3. Results : GOYT inhibited passive cutaneous anaphylaxis and acetic acid-induced vascular permeability by oral administration. All the concentrations of GOYT from 0.1 to 5 mg/ml didn't have an effect on cell viability and cytotoxicity. b-hexosaminidase release in RBL-2H3 was significantly reduced by 2 and 5 mg/ml of GOYT. Conclusion : These results indicate that GOYT have inhibition effects on immediate type hypersensitivity .

• YAKHAK HOEJI
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• v.47 no.2
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• pp.69-77
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• 2003

Arachidonic acid (AA), which is stored in membrane glycerophospholipids, is liberated by phospholipase $A_2$ (PLA$_2$) enzymes and is sequentially converted to cyclooxygenases (COXs) and lipoxygenases (LOXs) then to various bioactive PGs, and LTs. In order to find the specific inhibitors of AA metabolism especially PLA$_2$, COX-2, 5-LO and lyso PAF acetyltransferase, 120 Korean residential plants extracts were evaluated for their inhibitory activity on PGD$_2$, LTC$_4$ production from cytokine-induced mouse bone marrow-derived mast cells (BMMC) and arachidonic acid released from phospholipid and PAF production from lyso PAF. From this screening procedure, methanol extract of ten indigenous plant such as Salix gracilistyla, Sedum kamtschaticum, Cirsium chanroenicum, Hypericum ascyron, Astilbe chinensis, Agrimonia pilosa, Aristolochia manshuriensis, Vodia daniellii, Pyrola japonica, Styrax obassia were found to inhibit production of inflammatory mediators in vitro assay system.

• The Journal of Internal Korean Medicine
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• v.25 no.2
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• pp.174-182
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• 2004

Object : This study investigates Jaeumganghwa-tang(JGT) has been used for the purpose of prevention and treatment of allergic inflammatory diseases. This study was to investigate the biological effects of JGT. Methods : Cytotoxcicity and inflammatory cytokines secretion with human mast cells(HMC-1) were examined. HMC-1 cells were stimulated with phorbol l2-myristate 13-acetate (PMA) and calcium ionophore A23l87. JGT by itself had no effect on cytotoxicity of HMC-1. The effects of JGT on the secretion of tumor necrosis factor-alpha(TNF-${\alpha}$) and interleukin(IL)-6 from HMC-1 were evaluated with enzyme-linked immunosorbent assay(ELISA). Result : It was found that JGT inhibited PMA plus A23187-induced TNF-${\alpha}$ and IL-6 secretion. JGT also inhibited the $NF-{\kappa}$B(p50) expression. Conclusion : These results suggest that JGT inhibits the secretion of inflammatory cytokines in HMC-1 cells through blockade of $NF-{\kappa}B$ activation. Taken together, these effects support a role for JGT as a therapeutic agent in treatment of allergic inflammatory diseases such as asthma.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.3
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• pp.241-247
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• 2014

To investigate the underlying mechanisms of C18 fatty acids (stearic acid, oleic acid, linoleic acid and ${\alpha}$-linolenic acid) on mast cells, we measured the effect of C18 fatty acids on intracellular $Ca^{2+}$ mobilization and histamine release in RBL-2H3 mast cells. Stearic acid rapidly increased initial peak of intracellular $Ca^{2+}$ mobilization, whereas linoleic acid and ${\alpha}$-linolenic acid gradually increased this mobilization. In the absence of extracellular $Ca^{2+}$, stearic acid ($100{\mu}M$) did not cause any increase of intracellular $Ca^{2+}$ mobilization. Both linoleic acid and ${\alpha}$-linolenic acid increased intracellular $Ca^{2+}$ mobilization, but the increase was smaller than that in the presence of extracellular $Ca^{2+}$. These results suggest that C18 fatty acid-induced intracellular $Ca^{2+}$ mobilization is mainly dependent on extracellular $Ca^{2+}$ influx. Verapamil dose-dependently inhibited stearic acid-induced intracellular $Ca^{2+}$ mobilization, but did not affect both linoleic acid- and ${\alpha}$-linolenic acid-induced intracellular $Ca^{2+}$ mobilization. These data suggest that the underlying mechanism of stearic acid, linoleic acid and ${\alpha}$-linolenic acid on intracellular $Ca^{2+}$ mobilization may differ. Linoleic acid and ${\alpha}$-linolenic acid significantly increased histamine release. Linoleic acid (C18:2: ${\omega}$-6)-induced intracellular $Ca^{2+}$ mobilization and histamine release were more prominent than ${\alpha}$-linolenic acid (C18:3: ${\omega}$-3). These data support the view that the intake of more ${\alpha}$-linolenic acid than linoleic acid is useful in preventing inflammation.

• Journal of Ginseng Research
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• v.43 no.4
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• pp.635-644
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• 2019

Background: To increase the pharmacological effects of red ginseng (RG, the steamed root of Panax ginseng Meyer), RG products modified by heat process or fermentation have been developed. However, the antiallergic effects of RG and modified/fermented RG have not been simultaneously examined. Therefore, we examined the allergic rhinitis (AR)-inhibitory effects of water-extracted RG (wRG), 50% ethanol-extracted RG (eRG), and bifidobacteria-fermented eRG (fRG) in vivo. Methods: RBL-2H3 cells were stimulated with phorbol 12-myristate-13-acetate/A23187. Mice with AR were prepared by treatment with ovalbumin. Allergic markers IgE, tumor necrosis factor-${\alpha}$, interleukin (IL)-4, and IL-5 were assayed in the blood, bronchoalveolar lavage fluid, nasal mucosa, and colon using enzyme-linked immunosorbent assay. Mast cells, eosinophils, and Th2 cell populations were assayed using a flow cytometer. Results: RG products potently inhibited IL-4 expression in phorbol 12-myristate-13-acetate/A23187-stimulated RBL-2H3 cells. Of tested RG products, fRG most potently inhibited IL-4 expression. RG products also alleviated ovalbumin-induced AR in mice. Of these, fRG most potently reduced nasal allergy symptoms and blood IgE levels. fRG treatment also reduced IL-4 and IL-5 levels in bronchoalveolar lavage fluid, nasal mucosa, and reduced mast cells, eosinophils, and Th2 cell populations. Furthermore, treatment with fRG reduced IL-4, IL-5, and IL-13 levels in the colon and restored ovalbumin-suppressed Bacteroidetes and Actinobacteria populations and ovalbumin-induced Firmicutes population in gut microbiota. Treatment with ginsenoside Rd significantly alleviated ovalbumin-induced AR in mice. Conclusion: fRG and ginsenoside Rd may alleviate AR by suppressing IgE, IL-4, IL-5, and IL-13 expression and restoring the composition of gut microbiota.

• Journal of Acupuncture Research
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• v.39 no.1
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• pp.40-48
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• 2022

Background: This study was performed to determine the effects of liposome-encapsulated bee venom (BV) treatment of inflammatory factors in atopic dermatitis (AD) compared with BV treatment. Methods: AD was induced by phthalic anhydride in mice and the effects of BV liposomes were measured. Using Leica Application Suite, thickened epidermis and dermis were measured after BV liposome treatment (0.05 and 0.1 ㎍/mL). The number of stained mast cells and the concentration of immunoglobulin (Ig)E were measured. Serum IgE concentration was analyzed using an enzyme-linked immunosorbent assay. The serum concentrations of interleukin (IL)-1, IL-4, and IL-6 inflammatory cytokines were measured. The levels of messenger ribonucleic acid expression of proinflammatory cytokines and chemokines were measured using reverse transcription polymerase chain reaction. Inhibition of mitogen-activated protein kinase activation, was analyzed on western blot. To measure the transcriptional activity (NF-κB inhibition by BV liposomes), western blots (p65, p-IκB, p50, and IκB) were also performed. Results: The weight of lymph nodes, serum IgE concentrations, morphological changes in the skins from the backs of the mice, and mast cell numbers in inflamed tissues were noticeably lower in the BV liposome treatment group compared with the BV treatment group. The concentrations of pro-inflammatory cytokines (IL-1, IL-4, IL-6) and chemokines (TSLP, CCL22) were also reduced. Activation of mitogen-activated protein kinase (p-ERK and p-p38), and transcriptional activity (p65, p-IκB, p50, and IκB) was strongly suppressed in the BV liposome group. Conclusion: BV liposomes may have a better therapeutic effect than BV for the treatment of AD.

• Herbal Formula Science
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• v.31 no.4
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• pp.315-325
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• 2023

Objectives : Recently, research has been actively conducted on the efficacy of complexes based on oriental medicine prescriptions for improving immune activity and allergies. In this study, In this study, we aimed to examine the effect of Angelica gigas Nakai and Corni fructus extract (AC), medicinal herbs, among candidate drugs derived through preliminary experiments with various components of oriental medicine prescriptions for allergies, on allergies in RBL-2H3 cells. Methods : We evaluated the effect of the ethanol extract of Ulmus on the allergic inflammatory response in anti-DNP-IgE activated DNP-HSA in RBL-2H3 cells. Cell toxicity was determined by WST-1 assay and the markers of degranulation such as beta-hexosaminidase, histamine, TNF-α and IL-6 production of inflammatory mediators and FcεRI-mediated expression. Results : The results showed that treatment with AC extract (20, 40 and 80㎍/㎖) noncytotoxic levels and significantly inhibited the release of β-hexosaminidase, histamine and the production of TNF-α and IL-6 in RBL-2H3 by the antigen stimulation. Conclusions : These results indicate that AC extract exhibits anti-allergic activity through inhibition of degranulation and inhibition of inflammatory mediators and cytokine release. These findings suggest that AC extract may have potential as a prophylactic and therapeutic agent for the treatment of various allergic diseases.

• Journal of Acupuncture Research
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• v.19 no.2
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• pp.65-77
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• 2002

Objective : This study was undertaken to determine which compound of Bee Venom for herb-acupuncture has cytotoxicity on mouse mast cell line. Methods : We compared crude bee venom and its compounds such as melittin, mast cell degranulating peptide (MCD peptide), apamin with control groups on cytotoxicity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results & Conclusion : 1. Crude bee venom showed significant cytotoxic effect(p<0.01) in 1 hour treatment with $1{\mu}g/m{\ell}$ in comparison with control group in 1 hour treatment with low concentration of $10-4{\mu}g/m{\ell}$, $10-3{\mu}g/m{\ell}$, $10-2{\mu}g/m{\ell}$, $10-1{\mu}g/m{\ell}$ and $1{\mu}g/m{\ell}$, but it showed no significant cytotoxic effect in 6 hours treatment. 2. Melittin group showed no significant cytotoxic effect in comparison with control group in 1 and 6 hours treatment with low concentration of $10-4{\mu}g/m{\ell}$, $10-3{\mu}g/m{\ell}$, $10-2{\mu}g/m{\ell}$, $10-1{\mu}g/m{\ell}$ and $1{\mu}g/m{\ell}$. 3. MCD peptide and Apamin group showed no significant cytotoxic effect in comparison with control group in 1 and 6 hours treatment with low concentration of $10-4{\mu}g/m{\ell}$ $10-3{\mu}g/m{\ell}$, $10-2{\mu}g/m{\ell}$, $10-1{\mu}g/m{\ell}$ and $1{\mu}g/m{\ell}$. 4. Crude bee venom showed significant cytotoxic effect(p<0.01) in 1 and 6 hours treatment in comparison with control group in 1 and 6 hours treatment with high concentration of $10{\mu}g/m{\ell}$, $20{\mu}g/m{\ell}$ and $102{\mu}g/m{\ell}$. 5. Melittin group showed significant cytotoxic effect(p<0.01) in 1 hour treatment in comparison with control group in 1 hour treatment with high concentration of $10{\mu}g/m{\ell}$ but it showed no significant cytotoxic effect in 6 hours treatment. 6. Crude bee venom and its compounds have more cytotoxic effect in 1 hour treatment than in 6 hours treatment. It means cytotoxicity tends to decrease according to the treatment time.