• Biomolecules & Therapeutics
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• v.29 no.5
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• pp.492-497
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• 2021

Levels of sphingosine 1-phosphate (S1P), an intercellular signaling molecule, reportedly increase in the bronchoalveolar lavage fluids of patients with asthma. Although the type 4 S1P receptor, S1P₄ has been detected in mast cells, its functions have been poorly investigated in an allergic asthma model in vivo. S1P₄ functions were evaluated following treatment of CYM50358, a selective antagonist of S1P₄, in an ovalbumin-induced allergic asthma model, and antigen-induced degranulation of mast cells. CYM50358 inhibited antigen-induced degranulation in RBL-2H3 mast cells. Eosinophil accumulation and an increase of Th2 cytokine levels were measured in the bronchoalveolar lavage fluid and via the inflammation of the lungs in ovalbumin-induced allergic asthma mice. CYM50358 administration before ovalbumin sensitization and before the antigen challenge strongly inhibited the increase of eosinophils and lymphocytes in the bronchoalveolar lavage fluid. CYM50358 administration inhibited the increase of IL-4 cytokines and serum IgE levels. Histological studies revealed that CYM50358 reduced inflammatory scores and PAS (periodic acid-Schiff)-stained cells in the lungs. The pro-allergic functions of S1P₄ were elucidated using in vitro mast cells and in vivo ovalbumin-induced allergic asthma model experiments. These results suggest that S1P₄ antagonist CYM50358 may have therapeutic potential in the treatment of allergic asthma.

• 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.

• Korean Journal of Pharmacognosy
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• v.50 no.4
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• pp.277-284
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• 2019

Rumex crispus is known to have anticancer, antioxidant, antibacterial, and bone loss inhibitory activities. Mast cells are critical immune cells that induce a type 1 IgE-mediated allergic reaction. However, there are no reports of inhibitory effects of Rumex crispus on mast cells and allergic reactions. In this study, we performed some experiments to investigate whether Rumex crispus ethanol extract(RCE) has any inhibitory effect on antigen-induced type I allergic response in vitro and in vivo. RCE inhibited degranulation of IgE-mediated mast cells(IC₅₀, ~57 ㎍/ml) and cytokine production such as TNF-α and IL-4 in a dose-dependent manner. In vivo, RCE significantly inhibited passive cutaneous anaphylaxis(PCA)(ED₅₀, ~198 mg/kg) in mice. Furthermore, RCE inhibited degranulation of MCs in ear tissue of mice with PCA. Mechanism studies showed that RCE inhibited the activation of Syk and Syk-dependent pathway such as LAT, PLC-γ, Akt, and MAP Kinase. Our results demonstrate for the first time that RCE inhibits type I hypersensitive response by suppressing the activity of Syk in mast cells, thereby reducing degranulation and cytokine production. Taken together, RCE could be used as a novel therapeutic material to suppress allergic diseases.

• BMB Reports
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• v.28 no.3
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• pp.210-215
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• 1995

Effects of staurosporine, genistein and pertussis toxin on PMA-induced superoxide generation and degranulation in neutrophils were investigated. Their effects were also examined in C5a-stimulated superoxide generation. PMA-induced superoxide generation was inhibited by staurosporine but was not affected by pertussis toxin. Genistein enhanced the stimulatory effect of PMA in a dose dependent fashion. C5a-induced superoxide generation was inhibited by staurosporine, genistein and pertussis toxin. An NADPH oxidase system of resting neutrophils was activated by PMA, and the stimulatory effect of PMA was inhibited by staurosporine but was not affected genistein and pertussis toxin. The activity of NADPH oxidase in the membrane fraction of PMA-activated neutrophils was not affected by staurosporine and genistein. PMA-induced acid phosphatase release was inhibited by staurosporine and genistein, whereas the effect of pertussis toxin was not detected. These results suggest' that the role of protein tyrosine kinase in neutrophil activation mediated by direct activation of protein kinase C may be different from receptor-mediated activation. The action of protein kinase C on the respiratory burst might be affected by the change of protein tyrosine kinase activity.

• The Korean Journal of Food And Nutrition
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• v.15 no.4
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• pp.382-385
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• 2002

It is well known that the Petasites japonicum have been used for a long time in traditional medicine for the treatment of allergic diseases such as lacquer poisoning and asthma. Anti-allergic actions of Petasites japonicum extracts were asessed by testing their effects on the degranulation of mast cells. For this, hexosaminidase released (degranulation marker) from RBL-2H3 cells(mast cell line) was used. At the concentration of 300 $\mu\textrm{g}$/mL of the methanol, ethylacetate and hot water extract, the degranulation of RBL-2H3 cells were inhibited 83.33, 69.75 and 35.4%, respectively. These results suggest that the Petasites japonicum could be provide a effective resource for the control of allergic diseases.

• 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.

• Archives of Pharmacal Research
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• v.22 no.3
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• pp.320-323
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• 1999

The anti-allergic actions of the leaves of Castanea crenata (Fagaceae) were studied. The water extract demonstrated potent anti-allergic actions in in vivo and in vitro experiments. The oral or intraperitoneal administration of the extract (100 or 200 mg/kg) caused a significant inhibition of the 48 hr-PCA (up to 90%) and the vascular permeability induced by histamine or serotonin in rats (about 80%). The anaphylactic release of ${\beta}$-hexosaminidase for RBL-2H3 cells was also significantly inhibited by the extract in as dose-dependent manner with an IC50 value of 230 $\mu\textrm{g}$/ml. The activity-guided fractionation of the extract, based on the determination of inhibitor effect upon the release of ${\beta}$-hexosaminidase, led to the isolation of quercetin as an active principle responsible for the inhibition of degranulation.

• Biomolecules & Therapeutics
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• v.29 no.4
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• pp.427-433
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• 2021

Free fatty acid receptor 2 (FFA2, also known as GPR43), a G-protein-coupled receptor, has been known to recognize short-chain fatty acids and regulate inflammatory responses. FFA2 gene deficiency exacerbated disease states in several models of inflammatory conditions including asthma. However, in vivo efficacy of FFA2 agonists has not been tested in allergic asthma. Thus, we investigated effect of 4-chloro-α-(1-methylethyl)-N-2-thiazoylylbenzeneacetanilide (4-CMTB), a FFA2 agonist, on antigen-induced degranulation in RBL-2H3 cells and ovalbumin-induced allergic asthma in BALB/c mice. Treatment of 4-CMTB inhibited the antigen-induced degranulation concentration-dependently. Administration of 4-CMTB decreased the immune cell numbers in the bronchoalveolar lavage fluid and suppressed the expression of inflammatory Th2 cytokines (IL-4, IL-5, and IL-13) in the lung tissues. Histological studies revealed that 4-CMTB suppressed mucin production and inflammation in the lungs. Thus, results proved that FFA2 functions to suppress allergic asthma, suggesting 4-CMTB activation of FFA2 as a therapeutic tool for allergic asthma.

• Korean Journal of Veterinary Research
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• v.31 no.3
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• pp.343-353
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• 1991

In order to investigate the histopathological, mechanism of Rompun-induced shock, the development of mammary carcinoma, the numerical changes and the morphological findings of the mast cells appeared in the carcinoma were microscopically observed in the rat treated with DMBA and each chemical of compound 48/80 and Rompun. Also mast cell degranulation induced by Rompun was observed with electron microscope. The results observed were summarized as follows: Tumor appeared in 100% of the animals. Tumors grew more rapidly to $10{\times}10mm$ in rats depleted of mast cells ($37.7{\pm}4.2$ days) than was observed in the control group ($42.5{\pm}4.7$ days) (p<0.005). The mean number of tumors per rat was $2.8{\pm}1.3$ in the compound 48/80- treated group in contrast to $3.4{\pm}1.3$ in the control group. No significant difference was apparent in the tumor induction time of Rompun treated group compared with the compound 48/80-treated group, but the tumor measuring at least $10{\times}10mm$ appeared more quickly in the Rompun treated group than in the control group (p<0.005). The numbers of mast cells in the control group were inclined to increase significantly according to the mammary tumor development (p<0.005). In contrast, the mast cells were fewer significantly in the compound 48/80-treated group and Rompun-treated group than in the control group (p<0.005). The numbers of mast cells in the compound 48/80-treated group and Rompun-treated group were inclined to reduce significantly according to the stages of the mammary carcinoma growth in contrast to the control group respectively. The ultrastructural morphologies of mast cells at 30 minutes after Rompun injection were appeared many normal granules in the cytoplasm, but many normal and degranulated granules were scattered along the cell membrane. And at 1 hour after Rompun injection mast cell granules were disappeared nearly or rarely seen. many long cytoplasmic projections were folded back to adhere to their own surface membrane. and mast cells resulted in a reduced size of these cells. Otherwise. compound 48/80 caused extensive degranulation of mast cells by disrupting cell membrane. but mast cell degranulation by Rompun was observed exocytosis of granules through a channel. From the above results. it is concluded that the Rompun may give rise to the dealth of animals as a shock caused by mast cell degranulation.

• Korean Journal of Plant Resources
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• v.30 no.6
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• pp.662-669
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• 2017

Rubia cordifolia has been used to treat diseases for many years in China and India. Although the biological properties and major compounds of R. cordifolia have been extensively studied, the underlying mechanisms of its biological effects remain elusive. In terms of immunological effects, anti-inflammation effect of macrophage (Raw 264.7) simply has been reported. In this study, R. cordifolia was extracted in 70% ethanol and the extract did not affect to macrophage (Raw 264.7) pro-inflammation and T cell (Molt-4). However, in mast cell (RBL-2H3), it showed inhibition of degranulation. The inducing inhibitory effect on degranulation was related to concentration dependent variation in phosphorylation of ERK-1/2 and upregulating the JNK phosphorylation in RBL-2H3 cells. Based on these data, we concluded that R. cordifolia newly have anti-allergenic effects in RBL-2H3 and might be used as a therapeutic agent to treat or prevent allergic diseases such as asthma and atopic dermatitis.