• Korean Journal of Acupuncture
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• 제21권3호
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• pp.97-104
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• 2004

Objective We investigated the effect of Saururus chinensis (Lour.) Baill. aquacupuncture (SCB) on anaphylaxis in mice. Methods : We conformed compound 48/80-induced mesenteric mast cell degranulation, active systemic anaphylatic shock and histamine release. Also observed acetic acid-induced vascular permeability and anti-dinitrophenyl (DNP) IgE-mediated passive cutaneous anaphylaxis. Results : SCB inhibited mesenteric mast cell degranulation and active systemic anaphylatic shock induced by compound 48/80 dose-dependently. When SCB was pretreated by intra-peritoneal injection, the serum histamine levels were reduced. SCB also significantly inhibited acetic acid-induced vascular permeability. In addition, SCB showed a significant inhibitory effect on anti-dinitrophenyl (DNP) IgE-mediated passive cutaneous anaphylaxis. Conclusion : These results indicated that SCB inhibits anaphylatic reaction.

• Biomolecules & Therapeutics
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• 제30권6호
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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.

• 생명과학회지
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• 제33권2호
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• pp.176-182
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• 2023

석곡의 줄기는 전통 동양의학에서 위를 보하고, 진액을 보충하며, 열을 내리는 것에 사용되어 왔다. 본 연구에서는 RBL-2H3 세포에서 비만세포 탈과립과 TNF-α, IL-4, histidine decarboxylase (HDC) 발현에 미치는 석곡 열수추출물(DME)의 효과를 조사하였다. DME는 PMA와 Calcium ionophore 병행처리(PMACI)에 의해 유도되는 β-hexosaminidase 분비와 TNF-α, IL-4, HDC 발현을 현저히 억제하였다. 또한 PMACI에 의해 유도되는 NF-κB, AP-1 활성과 p38 kinase, extracellular signal-regulated kinase 1/2 (ERK1/2)과 c-Jun N-terminal kinase (JNK)의 인산화가 DME 전처리에 의해 저해되었다. 이러한 결과들은DME가 비만세포 탈과립을 억제하고, MAPKs/NF-κB/AP-1 신호전달 경로를 통해 TNF-α, IL-4, HDC 발현을 억제한다는 것을 시사한다. 본 연구결과들로 보아 DME는 과민반응과 염증성 질환을 치료하는 약물로 개발될 가능성을 가지는 것으로 사료된다.

• 대한본초학회지
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• 제28권5호
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• pp.39-44
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• 2013

Objectives : Allergy is an immune dysfunction caused by degranulation from mast cells in the early phase of allergic disease. The purpose of this study was to investigate the anti-allergic effect of fermented Angelicae gigantis Radix in human mast cell line, HMC-1. Method : The Angelicae gigantis Radix was fermented by Lactobacillus acidophilus. The cell toxicity of fermented Angelicae gigantis Radix(FAGR) was determined by MTT assay. The release of ${\beta}$-hexosaminidase from HMC-1 stimulated by phorbol-12-myristate 13-acetate (PMA) plus A23187 was determined by ${\beta}$-hexosaminidase assay. Also, the concentrations of cytokines (interleukin-$1{\beta}$, -6, -8 and tumor necrosis factor-alpha) were measured by enzyme-linked immunosorbent assay. The gene expression of COX-2 from HMC-1 stimulated by phorbol-12-myristate 13-acetate (PMA) plus A23187 was determined by reverse transcription polymerase chain reaction. The release of histamine on substance P-stimulated HMC-1 was measured by histamine assay. Result : The FAGR suppressed the release of ${\beta}$-hexosaminidase, a marker of degranulation, from HMC-1 stimulated by PMA plus A23187. The FAGR inhibited the production of interleukin-$1{\beta}$, -6, -8 and tumor necrosis factor-alpha. The FAGR inhibited the expression of COX-2 mRNA. The FAGR suppressed the release of histamine on substance P-stimulated HMC-1. Conclusion : These results provide that FAGR may be beneficial in the treatment of allergic inflammatory disease.

• 생약학회지
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• 제51권4호
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• pp.317-324
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• 2020

Mast cells play a key role in IgE-mediated allergic response. We investigated whether Swertia pseudochinensis Hara extract (SPE) inhibits IgE-mediated allergic response in mast cells and an allergic animal model. Additionally, we explored SPE's mechanism of action in mast cells. Our results showed that SPE inhibited both antigen-stimulated degranulation and the production of TNF-α and IL-4 in bone marrow-derived mast cells (BMMCs) and rat basophilic leukemia (RBL)-2H3 cells. SPE also suppressed allergic response in IgE-mediated passive cutaneous anaphylaxis (PCA) in mice. As for the mechanism of action of SPE in mast cells, it inhibited the activation of Syk kinase, a critical signaling protein in the FcεRI-mediated signaling pathway, and also the activation of LAT, a downstream adaptor protein of Syk. We further observed the reduced activation of mitogen-activated protein (MAP) kinases (P38, ERK1/2, and JNK) and Akt in mast cells. Our results described for the first time that SPE has an anti-allergic effect by suppressing mast cells through the inhibition of Syk kinase. Therefore, SPE may be useful for the treatment of type I allergic diseases.

• 대한소아치과학회지
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• 제28권1호
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• pp.72-81
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• 2001

Dendroaspis natriuretic peptide (DNP)는 최근에 green Mamba snake Dendroaspis angusticeps의 독(venom)에서 발견된 17개의 아미노산 disulfide링 구조를 포함하는 38개 아미노산 펩티드로 natriuretic peptide family와 그 구조가 비슷하다. Natriuretic peptide family는 사람과 흰쥐 비만세포로부터 히스타민을 유리시킨다고 알려져 있다. 그러나 DNP가 비만 세포로부터 히스타민을 유리 시키는 여부는 밝혀져 있지 않다. 본 연구는 DNP가 흰쥐 복강 비만세포로부터 히스타민을 유리시키는 여부와 함께 히스타민 유리기전을 구명하고자 실시되었다. 다양한 농도의 DNP를 흰쥐 복강 비만세포에 처리한 다음, 비만세포의 탈과립을 도립 광학현미경으로 관찰하였다. 히스타민 유리량은 방사효소법으로 측정하였고 세포내 칼슘 유입량과 cyclic GMP의 수준은 방사면역법으로 측정하였다. DNP는 흰쥐 복강 비만세포를 탈과립시켰고 농도가 증가함에 따라 비만세포로부터 히스타민 유리량이 증가되었다. 또한 DNP는 농도 증가에 비례하여 비만세포 안으로 세포밖의 칼슘을 유입시켰으며 세포안의 cyclic GMP의 수준을 증가시켰다. 이상의 결과로 미루어, DNP는 비만세포 안의 cyclic GMP와 칼슘의 농도를 증가시켜 비만세포로부터 히스타민을 유리시키는 것으로 생각된다.

• 생명과학회지
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• 제21권10호
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• pp.1364-1369
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• 2011

제 1형 과민반응은 비만세포에 의해 매개되는 알러지 반응으로서, 예기치 못한 알러젠에 의해 비만세포가 활성화 되어 탈 과립 되면서 히스타민등과 같은 여러 가지 매개체들을 분비하면서 과도하게 면역반응을 유도하게 된다. 주박(Korean rice wine lees)은 청주, 약주 등의 술을 걸러내는 과정에서 생기는 양조 부산물로서, 최근들어 청주를 걸러내는 과정에서 생기는 술 지게미의 생리기능에 대한 연구가 활발하게 진행되고 있다. 본 연구에서는 주박의 ethyl acetate (EA) 추출물을 이용하여 비만세포에서의 탈과립 억제 효과를 측정하였다. 그 결과 주박 EA 추출물이 탈과립의 표지인 ${\beta}$-hexosaminidase의 양을 농도 의존적으로 억제하는 것을 관찰하였고, 이러한 탈과립억제 현상이 다양한 사이토카인 중 IL-3과 IL-13의 양을 감소시킴으로써 매개된다는 사실을 RT-PCR을 통해 확인하였다. 또한 쥐에서 passive cutaneous anaphylaxis (PCA)를 유도하여 EA를 경구투여 했을 때 anaphylactic 증상을 효과적으로 억제하는 것을 관찰하였다. 이러한 결과들은 주박 EA 추출물이 항 알러지 약물의 개발에 잠재적인 후보물질이 될 수 있음을 시사한다.

• 동아시아식생활학회지
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• 제14권5호
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• pp.425-437
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• 2004

Medicinal plants are of great importance in providing healthcare to a large portion of the population in Korea. A number of plants are described in Dong-Ui-Bo-Gam for use in the treatment of allergic disorders, namely psoriasis, eczema, bronchial asthma, etc. In this study, we evaluated the effect of AllerQ, which is multi-complexes of various plants extracts such like Mori folium, Scutellaria baicallensis, Glycyrrhiza uralnsis, Mentha sacharinensis and Poncirus trifoliata on compound 48/80 induced anaphylactic shock, ovalbumin induced asthma in vivo and anti-IgE antibody induced hypersensitivity in vitro. We found antianaphylactic or antiallergic properties of AllerQ when given orally. AllerQ for prophylactic treatment for anaphylactic shocks have produced good results. AllerQ may modulate various aspects of immune function and allergic inflammation. In the present study, we analyse the effects of AllerQ on mast cell degranulation, mortality, cAMP/cGMP, O₂, H₂O₂ level, cyokine production and on the elicitation of IgE-mediated mast cell-dependent allergic inflammation in vivo and in vitro. We have established that AllerQ inhibited histamine release, cAMP/cGMP, O₂, H₂O₂ level, IL-4, tumor necrosis factor-alpha(TNF-α) and IL-6 production without having any significant physical change. These effects have been observed in mast cell(in vitro) and serum(in vivo) derived from three different origins that were activated by either immunological or non-immunological stimuli. These results suggest that the antianaphylactic and antiasthma tic action of AllerQ may be associated with an increase in the intracellular inhibition of the cAMP phosphodiesterase. Furthermore, AllerQ identified as potent inhibitors on O₂, H₂O₂ and cytokine activity. these data suggest that AllerQ may have an inhibitory role in mast cell-mediated allergic inflammation, and thus might be considered as an useful functional food.

• 대한본초학회지
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• 제32권6호
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• pp.9-15
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• 2017

Objectives : Traditional medicines isolated from natural products often have positive effects in the prevention and healing of various immune disorders, such as allergy and atopic inflammation. Scrophulariae Radix (SR) been used in oriental medicine used for treatment of acute and chronic inflammatory diseases. Mast cells are known to play important roles in the initiation of allergic reactions. In this study, we investigated the effects of SR ethanol extract on inflammatory responses in IgE-stimulated RBL-2H3 mast cells. Methods : Rat basophilic leukemia RBL-2H3 cells were purchased from Korean Cell Line Bank (KCLB No. 22256). Cell viability was measured by MTT assay. Assays for ${\beta}-Hexosaminidase$ Secretion : RBL-2H3 cells were sensitized with dinitrophenyl-ImmunoglobulinE (DNP IgE). The next antigen DNP-BSA ($25ng/m{\ell}$) was added for 10 minutes and the reaction was terminated after 5 minutes in the ice bath. To determine ${\beta}-Hexosaminidase$ release, supernatants were aliquoted into 96-well plates. Samples were mixed with substrate solution and incubated for 1 h at $37^{\circ}C$. Absorbance was measured with a spectrophotometer at 405 nm. IL-4 and tumor necrosis $factor-{\alpha}$($TNF-{\alpha}$) concentrations in cell culture supernatants were measured using enzyme-linked immunosorbent assay (ELISA) kits. Results : The cytotoxicity of SRE in RBL-2H3 cells was less than 5%. SRE inhibited DNP-IgE-imduced degranulation of mast cells in RBL-2H3 cells. Also significantly decreased the levels of inflammatory cytokine, IL-4 and TNF-alpha. In this study, the SRE showed potential anti-allergic and antiinflammatory. Conclusions : These results indicate that SRE could be inhibit the allergic response through suppressing the mast cell activation.

• 약학회지
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• 제41권5호
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• pp.647-651
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• 1997

We studied the effects of the powders of Spirulina platensis (SPP) on anaphylactic reactions. SPP inhibited systemic anaphylaxis induced by compound 48/80 in rats. SPP also inhibited local anaphylaxis activated by anti-dinitrophenyl(DNP) IgE. Moreover, SPP dose-dependently inhibited histamine release in rat peritoneal mast cells activated by compound 48/80 or anti DNP-IgE. These results suggest that SPP may contain compounds with actions that inhibit mast cell degranulation in the rat.