• Biomolecules & Therapeutics
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• 제24권3호
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• pp.283-290
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• 2016

Oroxylum indicum has long been used in Asian traditional medicine to prevent and treat respiratory diseases, diabetes, diarrhea and other conditions. Oroxylin A is a flavone that is present in Oroxylum indicum and in Scutellaria baicalensis. Because the root extracts of both plants have been shown to have anti-allergic effects, the authors investigated whether oroxylin A is likely to have beneficial effects on allergic asthma using female Balb/c mice and rat RBL-2H3 mast cells. Antigen-induced degranulation was measured in vitro by measuring b-hexosaminidase activity. A murine ovalbumin-induced allergic asthma model was used to test the in vivo efficacy of oroxylin A. Sensitization and challenge of ovalbumin induced allergic asthma responses, the accumulations of eosinophils and Th2 cytokine levels in bronchoalveolar lavage fluid and lung tissues. Oroxylin A administration decreased numbers of inflammatory cells, especially eosinophils, and reduced the expression and secretion of Th2 cytokines, including IL-4 and IL-13, in lung tissues and bronchoalveolar lavage fluid. Histologic studies showed oroxylin A reduced inflammatory signs and mucin production in lungs. These findings provide evidence that oroxylin A has potential use as an anti-allergic therapeutic.

• 농촌의학ㆍ지역보건
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• 제34권3호
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• pp.316-323
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• 2009

본 연구는 천식과 골다공증유병유무와의 관련성을 알아봄으로써 골다공증의 예방 및 관리의 기초 자료로 제공하기 위해 시도되었다. 연구의 기초 자료는 ‘2008년 지역사회건강조사’ 를 이용하였다. 조사 시기는 2008년 9월부터 2008년 11월 까지였고, 충남의 7개 군 및 대전시 서구에 거주하는 19세 이상 주민 6,348명을 대상으로 하였다. 이 중 천식이 있다고 응답한 203명 및 골다공증이 있다고 대답한 465명의 특성을 질병이 없는 군의 특성과 비교하였다. 천식 유병유무와 골다공증 유병유무와는 유의한 상관관계가 있었고, 천식대상자 중에서 천식치료여부와 골다공증 유병유무와도 유의한 상관관계가 있었다. 추가로 좀 더 광범위한 연구 분석과 추적조사가 필요하리라 사료된다.

• IMMUNE NETWORK
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• 제22권6호
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• pp.45.1-45.15
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• 2022

Asthma is a chronic airway inflammatory disease characterized by reversible airway obstruction and airway hyperreactivity to various environmental stimuli, leading to recurrent cough, dyspnea, and wheezing episodes. Regarding inflammatory mechanisms, type 2/eosinophilic inflammation along with activated mast cells is the major one; however, diverse mechanisms, including structural cells-derived and non-type 2/neutrophilic inflammations are involved, presenting heterogenous phenotypes. Although most asthmatic patients could be properly controlled by the guided treatment, patients with severe asthma (SA; classified as a treatment-refractory group) suffer from uncontrolled symptoms with frequent asthma exacerbations even on regular anti-inflammatory medications, raising needs for additional controllers, including biologics that target specific molecules found in asthmatic airway, and achieving the precision medicine for asthma. This review summarizes the immunologic basis of airway inflammatory mechanisms and current biologics for SA in order to address unmet needs for future targets.

• The Korean journal of internal medicine
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• 제39권2호
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• pp.215-227
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• 2024

Asthma is characterized by airway obstruction and inflammation, and presents significant diagnostic and treatment challenges. The concept of endotypes has improved understanding of the mechanisms of asthma and has stimulated the development of effective treatment strategies. Sputum profiles may be used to classify asthma into two major inflammatory types: type 2-high (T2H) and type 2-low (T2L) asthma. T2H, characterized by elevated type 2 inflammation, has been extensively studied and several effective biologic treatments have been developed. However, managing T2L is more difficult due to the lack of reliable biomarkers for accurate diagnosis and classification. Additionally, conventional anti-inflammatory therapy does not completely control the symptoms of T2L; therefore, further research is needed to identify effective biologic treatments. This review provides new insights into the clinical characteristics and underlying mechanisms of severe T2L and investigates potential therapeutic approaches to control the disease.

• Biomolecules & Therapeutics
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• 제17권4호
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• pp.388-394
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• 2009

The cytokines which is produced by allergen-specific T helper (Th) cells play a pivotal role in the pathogenesis of asthma. Asthma is caused by exaggerated T-helper 2 (Th2)-based immune responses. It is suggested that controlling such Th2-based response is necessary for asthma therapy. The current therapies for asthma focus primarily on control of symptoms and suppression of inflammation, without affecting the underlying cause. So, we examined that anti-asthmatic drugs might have play a certain role in Th2/Th1 balance. Splenocytes isolated from ovalbumin (OVA)-sensitized mice cultured with anti-asthmatic drugs. It is well known that Th2 and Th1 immune responses can balance one another, as Th2 mediators suppress Th1 responses and Th1 mediators similarly inhibit Th2 responses. But salmeterol inhibits both of Th1 and Th2 mediators, which salmeterol is a suppressor of immune responses not only a suppressor of Th2-based immune responses. Aminophylline is a weak suppressor of immune responses. But ipratropium and cromoglycate don't have any suppressor effect to Th2-driven responses. They only have suppressor effect to Th1 immune responses. Salmeterol, ipratropium, aminophylline, and cromoglycate augmented mRNA levels of CRTH2, EP2, and IP2 receptors in OVA-sensitized splenocytes. It is well known that the up-regulation of CRTH2 - $PGD_2$ receptor - results in restraint of eosinophil recruitment and that the increment of IP and EP2 - $PGI_2$ and $PGE_2$ receptor, respectively - may induce the accumulation of cAMP that decrease the effector function of T cells. Moreover salmeterol and cromoglycate increase the mRNA expression of $PGD_2$ synthase. These findings indicate that anti-asthma agents may alleviate the immunological responses that cause the asthmatic diseases.

• 디지털융복합연구
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• 제14권6호
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• pp.317-323
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• 2016

본 연구의 목적은 백삼, 오미자, 맥문동, 길경, 감초 등으로 구성된 백삼복합물이 난알부민으로 유도된 천식 마우스에서의 천식개선에 대한 융복합 연구를 통한 효능을 확인하는 것입니다. 난알부민으로 천식을 유발한 마우스에 백삼복합물을 100 mg/kg과 300 mg/kg을 경구 투여한 후 혈청 내 Th2 사이토카인 IL-4, IL-5, IL-13을 루미넥스를 이용하여 측정하였다. 또한, 혈청과 혈액 내 난알부민 특이-IgE 수치와 호산구, BALF 내 총 세포수는 자동혈구계산기 및 현미경을 통해 측정하였다. 그 결과, 혈청 내 IL-4, IL-5, IL-13 및 난알부민 특이-IgE 수치가 대조군에 비해 각각 감소하였다. 또한, 혈액 내 호산구 및 BALF 내 총 세포수 역시 감소를 보였다. 이러한 결과는 백삼복합물이 Th2 사이토카인과 천식 요인에 대해 감소가 나타나 효과적인 항천식 치료 약물로서 사용될 수 있음을 시사하는 바이다.

• Tuberculosis and Respiratory Diseases
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• 제82권1호
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• pp.71-80
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• 2019

Background: Efficacy and safety of tiotropium bromide, a muscarinic receptor antagonist, in treatment of asthma have been reported. However, its effect on airway remodeling in chronic asthma of the elderly has not been clearly verified. The objective of this study was to investigate the effect of tiotropium and expression of muscarinic receptors as its related mechanism in an aged mouse model of chronic asthma with airway remodeling. Methods: BALB/c female mice age 6 weeks, 9 and 15 months were sensitized and challenged with ovalbumin (OVA) for three months. Tiotropium bromide was administered during the challenge period. Airway hyperresponsiveness (AHR) and pulmonary inflammation were measured. Parameters of airway remodeling, and expression levels of $M_2$ and $M_3$ receptors were examined. Results: Total cell with eosinophils, increased in the OVA groups by age, was decreased significantly after treatment with tiotropium bromide, particularly in the age group of 15 months. AHR and levels of interleukin (IL)-4, IL-5, and IL-13 were decreased, after tiotropium administration. In old aged group of 9- and 15-months-treated groups, hydroxyproline contents and levels of ${\alpha}$-smooth muscle actin were attenuated. Tiotropium enhanced the expression of $M_2$ but decreased expression of $M_3$ in all aged groups of OVA. Conclusion: Tiotropium bromide had anti-inflammatory and anti-remodeling effects in an aged mouse model of chronic asthma. Its effects seemed to be partly mediated by modulating expression $M_3$ and $M_2$ muscarinic receptors. Tiotropium may be a beneficial treatment option for the elderly with airway remodeling of chronic asthma.

• Biomolecules & Therapeutics
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• 제29권5호
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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.

• 한방안이비인후피부과학회지
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• 제28권4호
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• pp.74-91
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• 2015

Background and Objective : Asthma is a chronic inflammatory disease at the mucosa and is associated with excess production of Th2 cytokine and eosinophil accumulation in lung.Gamchomahwang-tangextract(GME) is one of the well known prescription used in oriental medicine for treating asthma. This study was designed to compare the anti-asthmatic effect of GME according to the ratio of 2 compounds.Methods : To examine the effects of GME on asthma, mice were sensitized with 100 ㎍ of OVA and 1 ㎎ of aluminum potassium sulfate(Alum; Sigma) intraperitoneally on day 1 and 15. From day 22, mice were challenged on 3 consecutive days with 5% OVA. The anti-asthmatic effects of GME were evaluated by enhanced pause(Penh), bronchoalveolar lavage fluids (BALF), inflammatory cytokine production and genes expression, serum IgE production. and histological change in lung tissue. GMEⅠ consists of ES and GU in the proportion 2:1(300 ㎎/㎏ group), GMEⅡ consist of ES and GU in the proprtion 4:1(300 ㎎/㎏ group).Results : GMEⅠ,Ⅱ generally inhibited lung inflammation, inflammatory cells infiltration and cytokine production and gene expression such as IL-4, IL-5 and IL-13 in BALF and serum IgE level. GMEⅡ significantly reduced the cytokine production and gene expression such as IL-4, IL-5 and IL-13 in BALF and GMEⅠ decreased cytokine production of IL-4, IL-13 in BALF and gene expression of IL-4, IL-5 in Lung. GMEⅡ potently inhibited the development of Penh and also reduced the number of eosinophil during OVA-induced AHR(airway hyper-reactivity). Overall the results show that GMEⅡ has more effect on inhibiting production, gene expression of cytokine, serum IgE level and development of Penh than GMEⅠ. Consequently, GMEⅡ might be more effective than GMEⅠ at inhibiting allergic asthma on the OVA-induced mice model.Conclusion : These results indicate that GME has a deep inhibitory effects on airway inflammation and hyperresponsiveness in mice model of asthma and that suppression of IL-4, IL-5, IL-13 expression and decrease of IL-4, IL-5, IL-13 production in BALF might contribute this effect. Hence, the results indicate that GME might be useful herbal medicine of allergic asthma. As a result, GMEⅡ mght be superior to GMEⅠ in the aspect of anti-asthmatic effect on the OVA-induced mice model.

• Journal of Ginseng Research
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• 제45권4호
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• pp.482-489
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• 2021

Background: Asthma is an incurable hyper-responsive disease of the pulmonary system that is caused by various allergens, including indoor and outdoor stimulators. According to the Global Asthma Network, 339 million people suffered from asthma in 2018, with particularly severe forms in children. Numerous treatments for asthma are available; however, they are frequently associated with adverse effects such as growth retardation, neurological disorders (e.g., catatonia, poor concentration, and insomnia), and physiological disorders (e.g., immunosuppression, hypertension, hyperglycemia, and osteoporosis). Methods: Korean Red Ginseng has long been used to treat numerous diseases in many countries, and we investigated the anti-asthmatic effects and mechanisms of action of Korean Red Ginseng. Eighty-four BALB/c mice were assigned to 6 treatment groups: control, ovalbumin-induced asthma group, dexamethasone treatment group, and 3 groups treated with Korean Red Ginseng water extract (KRGWE) at 5, 25, or 50 mg/kg/day for 5 days. Anti-asthmatic effects of KRGWE were assessed based on biological changes, such as white blood cell counts and differential counts in the bronchoalveolar lavage fluid, serum IgE levels, and histopathological changes in the lungs, and by examining anti-asthmatic mechanisms, such as the cytokines associated with Th1, Th2, and Treg cells and inflammation pathways. Results: KRGWE affected ovalbumin-induced changes, such as increased white blood cell counts, increased IgE levels, and morphological changes (mucous hypersecretion, epithelial cell hyperplasia, inflammatory cell infiltration) by downregulating cytokines such as IL-12, IL-4, and IL-6 via GATA-3 inactivation and suppression of inflammation via NF-κB/COX-2 and PGE₂ pathways. Conclusion: KRGWE is a promising drug for asthma treatment.