• Biomolecules & Therapeutics
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• v.30 no.6
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• pp.520-528
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• 2022

Mast cells are an effector cell that plays a pivotal role in type I hypersensitive immune responses. Mast cells exist in connective tissues, such as skin and mucosal tissue, and contain granules which contain bioactive substances such as histamine and heparin in cells. The granules of mast cells are secreted by antigen stimulation to cause the type I allergic hypersensitivity. In addition, stimulated by antigen, mast cells synthesize and secrete various eicosanoids and cytokines. While AT9283 is known to have anticancer effects, the therapeutic effect of AT9283 on allergic disorders is completely unknown. In this study, it was found that AT9283 reversibly inhibited antigen-IgE binding-induced degranulation in mast cells (IC₅₀, approx. 0.58 μM) and suppressed the secretion of the inflammatory cytokines IL-4 (IC₅₀, approx. 0.09 μM) and TNF-α (IC₅₀, approx. 0.19 μM). For a mechanism of mast cell inhibition, while not inhibiting Syk phosphorylation, AT9283 suppressed the activation of LAT, a downstream substrate protein of Syk, in a dose-dependent manner. As expected, AT9283 also inhibited the activation of PLCγ1 and Akt, downstream signaling molecules of Syk/LAT, and MAP kinases such as JNK, Erk1/2, and P38. In an in vitro protein tyrosine kinase assay, AT9283 directly inhibited Syk activity. Next, AT9283 dose-dependently inhibited passive cutaneous anaphylaxis (PCA), an IgE-mediated allergic acute response, in mice (ED50, approx. 34 mg/kg, p.o.). These findings suggest that AT9283 has potential to use as a new drug for alleviating the symptoms of IgE-mediated allergic disorders.

• Advances in Traditional Medicine
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• v.1 no.2
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• pp.21-28
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• 2000

We compared the effect between CAS and WAS(root, stem) on mast cell-mediated allergic reaction. CAS, WAS-root and WAS-stem, significantly inhibited compound 48/80-induced systemic allergic reaction(1g/kg) and histamine release from RPMC(1mg/ml). CAS, WAS-root and WAS-stem also inhibited passive cutaneous anaphylactic reaction. In addition, IgE-induced $TNF-{\alpha}$ secretion from RBL-2H3 was inhibited by pretreatment of CAS, WAS-root or WAS-stem$(0.01{\mu}g/ml)$. Taken together, inhibitory effect on mast cell-mediated allergic reactions of WAS-root is greater than those of WAS-stem but less than those of CAS.

• Biomolecules & Therapeutics
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• v.12 no.4
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• pp.235-241
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• 2004

Gagam-danguiemja (GDGJ), a traditional Korean prescription, has been used as therapeutics for atopic allergic diseases such as atopic dermatitis. To evaluate the atopic allergic effect of modified GDGJ, we investigated a possible effect of GDGJ on mast cell-mediated allergic reaction, cytokinases secretion and mRNA expression in vivo and in vitro. Mast cells are a potent source of mediators that regulate the inflammatory response in allergic reaction. In mice orally administered by GDGJ (0.01, 0.1 and 1.0 g/kg) for 1 h, compound 48/80-induced ear oedema was significantly reduced. TNF-${\alpha}$, IL-8, and IL-6 secretion were inhibited by GDGJ in the human mast cell line (HNC-1). But TNF-${\alpha}$, IL-8, and IL-6 mRNA expression were not inhibited by GDGJ at the dose of 0.01 mg/ml. These findings may help in understanding the mechanism of action of this herbal medication, leading to the control of mast cells in atopic allergic reaction like AD.

• 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.

• The Korea Journal of Herbology
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• v.29 no.3
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• pp.79-85
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• 2014

Objectives : In this study, we attempted to evaluate the effects of Careswell on human mast cell-mediated allergy inflammation in vitro and pruritogen-induced scratching behavior in vivo. Method : The Careswell was extract by distilled water. The anti-itching effects of Careswell were investigated on the compound 48/80 ($50{\mu}g/kg$) or histamine ($100{\mu}g/kg$) induced scratching behavior male ICR mice for 30 min by an observer blind. Terfenadine (10 mg/kg) was used as a positive control drug. The cell toxicity of Careswell was determined by 3-(4,5-dimethylthiazole-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay. The regulatory effect of Careswell on interleukin (IL)-6 and tumor necrosis factor (TNF)-${\alpha}$ levels was determined by enzyme-linked immunosorbent assay (ELISA) in phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI) stimulated human mast cells (HMC-1). Also, we evaluated the effect of Careswell on PMACI induced the activation of Nuclear factor-kappa B (NF-${\kappa}B$) into nucleus by Western blot analysis. Result : The results revealed that the oral administration of Careswell (200 mg/kg, p.o.) attenuated the compound 48/80 or histamine-induced scratching behavior in mice. We showed that Careswell significantly reduced the PMACI-induced the production of IL-6 (0.5-1 mg/ml) and TNF-${\alpha}$ (0.1-1 mg/ml). Additionally, Careswell significantly inhibited the activation of NF-${\kappa}B$ in PMACI-stimulated HMC-1. Conclusion : Collectively, the findings of this study provide us with a novel insight into the pharmacological actions of Careswell as a potential molecule for use in the treatment of allergic inflammation diseases.

• YAKHAK HOEJI
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• v.40 no.6
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• pp.679-683
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• 1996

The current study evaluates the capacity of eugenol to regulate immediate allergic reaction by control of histamine release. Administrations of eugenol (1M/kg, i.p.) at 60 min b efore and 5, 10 min after the compound 48/80 treatment (8mg/kg, i.p.) were shown the mortality rates as 0, 44.4, and 77.8%, respectively. A 60 min before administered group revealed a significant inhibition of serum histamine release compared with those of 5 and 10 min after the compound 48/80 injection. Eugenol (6-48mM) was also showed a dose-dependent activity on the compound 48/80-induced histamine release from the highly purified population of Alcian Blue-positive peritonea] mast cells. These results indicate that in vitro treatment with exogenous eugenol inhibited the active response of mast cell populations and modulated its characteristics.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.13 no.1
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• pp.141-156
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• 2000

Cloves are the dried flower buds of Syzygium aromaticum (L.) Mere et Perry (Myrtaceae). They have been successfully used for the management of various allergic disorders by oral administration in Korea. In this study, the author investigated the effect of an aqueous extract of Syzygium aromaticum on immediate-type hypersensitivity by anal administration. Anal administration of Syzygium aromaticum showed a marked inhibition rate in systemic hypersensitivity with a dose of 1 mg/kg 1 hr before intraperitoneal injection of compound 48/80. Anal administration of Syzygium aromaticum significantly reduced plasma histamine contents induced by compound 48/80. Anal administration of Syzygium aromaticum (1 mg/kg) also inhibited to $61.4\%$ (P<0.01) local a1lergic reaction activated by anti-dinitrophenyl (DNP) IgE. In addition, Syzygium aromaticum dose-dependently inhibited the histamine release from the peritoneal mast cells by compound 48/80 or anti-DNP IgE. When Syzygium aromaticum was added, the level of cAMP in peritoneal mast cells transiently and significantly increased about 47-fold at 10 second compared with that of basal cells. These results provide evidence that anal therapy of Syzygium aromaticum may be beneficial in the treatment of systemic and local immediate-type hypersensitivity by inhibition of histamine release from mast cells in vivo and in vitro.

• Korean Journal of Pharmacognosy
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• v.40 no.3
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• pp.218-223
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• 2009

The roots of Rumecis Radix have been used for the treatment of heat phlegm, jaundice, constipation, scabies and uterine hemorrhage. The aim of this study was to confirm whether Rumecis Radix water extract (RJWE) has a preventive effect on the development of atopic dermatitis (AD) in 2,4-dinitrochlorobenzene (DNCB)-applied BALB/c mice. Oral administration (12.5 mg/kg, 25 mg/kg) and topical application (0.5 mg/mouse, 1.0 mg/mouse) of RJWE decreased the development of AD-like skin lesions, ear swelling, spleen weight and total serum IgE. RJWE significantly also inhibited the infiltration of mast cells in the dorsal skin. Furthermore, the release of histamine from rat peritoneal mast cells (RPMCs) was suppressed significantly. These results suggest that the inhibitory effect of RJWE on AD might be associated with mast cells.

• Journal of Veterinary Clinics
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• v.30 no.2
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• pp.131-133
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• 2013

A 9-year-old, intact female Jindo dog weighing 23 kg was presented to the Veterinary Medical Teaching Hospital of Chungnam National University with a history of two months of ocular discharge. Initial ocular examination showed a 2 cm elongated mass arising from the ventral bulbar conjunctiva of the left eye. Ocular ultrasound, performed to rule out any orbital and intraocular involvement, was negative. Thoracic radiographs and abdominal ultrasonography revealed no abnormalities. Fine needle aspiration (FNA) of mass was performed. Aspiration cytology showed the presence of a round cell population mostly characterized. A moderate amount of eosinophils was present among round cells. The mass was excised and identified hitologically as a mast cell tumor. Six months after surgical treatment, thoracic radiographs and abdominal ultrasonography did not reveal any clinical signs of local recurrence or metastatic disease.

• Korean Journal of Medicinal Crop Science
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• v.14 no.5
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• pp.282-288
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• 2006

The effects of extracts from various Oriental medicinal herbs on mast-cell-mediated allergic reactions were investigated in this study. Out of these extracts, the medicinal herb Atractylodis rhizoma alba exhibited the most potent activity in the cells, with $IC_50$ values of $20.5\;{\mu}g/ml$, by DNP-BSA and $33.04\;{\mu}g/ml$, by compound 48/80. Similar to the in vitro activity, Atractylodis rhizoma alba inhibited compound-48/80-induced systemic anaphylaxis by 31.3% at 300 mg/kg in mice. It also suppressed the secretion of $TNF-{\alpha}$, a major pro-inflammatory cytokine in the cells. These results may suggest that Atractylodis rhizoma alba shows anti-allergic activity in compound 48/80-induced anaphylactic mice through the inhibition of mast cells.