• 생명과학회지
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• 제18권10호
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• pp.1336-1341
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• 2008

기관지를 통하여 발병하는 염증은 대표적인 면역질환의 현상인데 천식이나 아토피 피부염 등에 나타난다. 신선초의 물 추출물이 항천식 활성을 나타내는지를 알아보기 위하여 ovalbumin으로 유도시킨 동물모델을 사용하였다. 마우스에 경구투여하여 폐의 조직을 Haematoxylin-Eosin 염색과 면역조직화학을 이용하여 인터루킨-4 및-13의 발현을 측정한 결과, 신선초의 물 추출물은 $CD4^+$ 세포의 수 및, 인터루킨-4 및 -13의 발현을 억제하는 것으로 나타났다. 이의 결과는 신선초의 물 추출물이 ovalbumin 으로 유도시킨 마우스의 천식 증상을 경감시키는 것으로 이의 활용이 기대된다.

• Tuberculosis and Respiratory Diseases
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• 제45권1호
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• pp.99-106
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• 1998

연구배경: 기관지 천식은 다양한 원인에 대한 기도 협착과 과민 반응을 특정으로 하는 기도 질환으로, 그 병인에 대한 연구를 임상적으로 시행하는 데에는 한계가 있어, 동물 천식 모형을 이용한 연구가 필요하다. 동물에서의 기도 저항의 측정은 주로 마취나 삽관 상태에서 침습적으로 측정되었으나, 최근 비침습적으로 의식이 있는 상태에서 일상호흡 중의 specific 기도 저항을 측정하는 방법들이 고안되었다. 이에 저자들은 기니픽에 allergen인 ovalbumin을 피하 주사하여 감작시킨 후, 의식이 있는 상태에서 ovalbumin과 methacholine을 각각 흡입시켜, 비침습적인 방법으로 specific 기도 저항을 측정함으로써 즉시형 기관지 수축 정도와 methacholine에 대한 기도 과민성의 변화를 연구하여 동물 천식 모형을 만들고자 하였다. 연구방법: 기니픽 30마리를 천식군 20마리, 대조군 10마리로 나누어, 천식군에서는 ovalbumin을 피하 주사하여 감작시킨 후, ovalbumin을 흡입(1% wt/vo1)으로 노출시켰고, 대조군은 생리 식염수를 동일한 방법으로 감작, 노출시켰다. specific 기도 저항(airway resistance $\times$ thoracic gas volume)은 의식이 있는 상태에서 비침습적으로 동물 body plethysmography를 사용하여, Pennock법으로 allergen 노출 3분전부터, 노출후 27분까지 3분 간격으로 30분간 측정하였다. Methacholine은 지속적으로 2배씩 농도를 증가하여, 각 농도에 대하여 3분 간격으로 흡입시킨 후, 통일한 방법으로 specific 기도 저항을 측정하여 기도 저항이 200% 이상 증가될 때의 methacholine 농도 ($EC_{200}R_L$)를 구하였다. 결 과: 천식군 20마리 중 65%인 13마리에서 ovalbumin 흡입에 대한 specific 기도 저항이 3분부터 증가하여 6분에 231.5%로 최고를 보이고 실험 측정 종료까지인 30분까지 대조군에 비하여 유의하게 증가된 상태로 지속되어 (p<0.001), 천식 모형이 형성되었다. Methacholine에 대한 기관지 과민 반응은 $EC_{200}R_L$가 대조군에서 평균 $0.446{\pm}0.287mg/ml$, 기하평균 $-1.429{\pm}0.976$였고, 천식군에서 형성된 천식 모형에서의 평균은 $0.149{\pm}0.075mg/ml$, 기하평균 $-2.923{\pm}0.760$으로 천식 모형에 있어서 methacholine에 대한 기관지 과민 반응이 대조군에서보다 2 배 높았다(p<0.0013).

• Biomolecules & Therapeutics
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• 제31권6호
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• pp.611-618
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• 2023

Rhizome of Alisma orientale has been used as a traditional medicine for treating kidney diseases in East Asian countries. Its inhibitory effects on hypersensitivity responses have been reported for methanol extracts, with alisol B 23-acetate (AB23Ac) being the most active constituent among six terpenes in inhibiting the direct passive Arthus reaction. However, whether AB23Ac has efficacy against allergic asthma has not been tested to date. The in vivo efficacy of AB23Ac in an ovalbumin (OVA)-induced allergic asthma mouse model was evaluated by administrating AB23Ac before OVA sensitization or OVA challenge in BALB/c mice. AB23Ac suppressed antigen-induced degranulation of RBL-2H3 mast cells in a concentration-dependent manner. The administration of AB23Ac both before OVA sensitization and OVA challenge greatly lowered pulmonary resistance and the increase in immune cell counts and inflammatory responses around the peribronchial and perivascular regions. In addition, the inflammatory cytokine levels of Th1/Th2/Th17 cells in the bronchoalveolar lavage fluid decreased in the AB23Ac-treated groups. AB23Ac reduced the number of PAS-stained cells in the lungs. Furthermore, a computer modeling study indicated that AB23Ac can bind tightly to spleen tyrosine kinase (Syk). These results suggest that AB23Ac may ameliorate allergic asthma by suppressing immune responses in dendritic cells during sensitization and in mast cells during challenge periods.

• 한방안이비인후피부과학회지
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• 제24권1호
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• pp.36-44
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• 2011

Objective : Propolis (PP) has been used in oriental medicine. PP has various biological activities. However, its immunoregulatory and anti-inflammatory activities have not been well studied. In this study, I investigated these activities of PP by using ovalbumin-induced allergic asthma in mice. Methods : To examine the effect of PP on allergic asthma, mice were sensitized with $100{\mu}g$ of OVA and 1mg of aluminum potasssium sulfate (Alum; Sigma) intraperitoneally on day 0 and 7. On day 14, mice were challenged on consecutive 3 days with 5% OVA and AHR was assessed 24 hours after the last challenge. To examine severity of AHR, I examined the population of eosinophiles and T cells in spleen and lung and cytokine production in T cells. Futhermore, I examined histological changes during the OVA-induced allergic asthma. Results and Conclusion : PP reduced the population of eosinophil and CD4+ T cells on the OVA-induced AHR mice model. PP also inhibited IL-4 production but increased INF-g production in T cells. These results suggest that PP may be beneficial material for allergic 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.

• 생명과학회지
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• 제22권3호
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• pp.298-305
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• 2012

Lutein은 식물에서 발견되는 carotenoid 계열에 속하는 물질로 항산화 기능을 가지고 있는 것으로 널리 알려져 있지만, 호흡기 질환과 관련하여 아직까지 lutein의 효능과 작용 기작이 잘 알려져 있지 않다. Ovalbumin (OVA)으로 유도한 천식(asthma) 생쥐모델에서 lutein은 기도 과민성을 억제하였고, 기관지 폐포 세척액에서 OVA의 감작에 의하여 증가한 각종 염증성 지표들을 감소시켰다. 또한, OVA의 감작에 의하여 증가한 제2형 협조 T 세포(Th2 cell)의 증가된 반응을 약화시키는 결과를 볼 수 있었다. 본 실험에서 lutein이 ovalbumin (OVA)으로 유도한 천식 생쥐 모델에서 제 2형 협조 T세포의 싸이토카인과 유전자 발현을 조절할 수 있는 면역약리학적 기능을 할 수 있는 물질로서의 가능성이 있음을 확인할 수 있었다.

• 대한의생명과학회지
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• 제16권2호
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• pp.83-90
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• 2010

Hesperidin, a member of the flavanone group of flavonoids, can be isolated in large amounts from the rinds of some citrus species [e.g., Citrus aurantium L. (bitter orange), Citrus sinensis L. (sweet orange) and Citrus unshiu Marcov. (satsuma mandarin)], and has been reported to have anticarcinogenic, antihypotensive and antimicrobial properties. Despite the efficacy of these polyphenolic compounds as immune modulators, the effects of the flavonoids are poorly understood about allergic effect. In this study, we investigated whether hesperidin could influence on Th1 and Th2 balance. Allergic reactions included an increase in the number of eosinophils in bronchoalveolar lavage (BAL) fluid, an increase in inflammatory cell infiltration into the lung tissue around blood vessels and airways, airway luminal narrowing, the development of airway hyper-responsiveness (AHR). The administration of hesperidin before the last airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. Accordingly, this study may provide evidence that hesperidin plays a critical role in the amelioration of the pathogenetic process of asthma in mice. These findings provide new insight into the immunopharmacological role of hesperidin in terms of its effects in a murine model of asthma, and also broaden current perspectives in our understanding of the immunopharmacological functions of hesperidin.

• 한방안이비인후피부과학회지
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• 제27권3호
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• pp.84-95
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• 2014

Objective : Ephedra sinica (ES) has has been used as remedy of allergic diseases for a long time in Korea. In the present study, we investigated the anti-allergic effects of ES on experimental allergic asthma mouse model using ovalbumin (OVA). Methods : BALB/c mice were sensitized and challenged with 100 ug of OVA and 1 mg of aluminum potassium sulfate of 0.2 ml phosphate-buffered saline(PBS) intraperitoneally on day 1 and 15. mice were challenged on 3 consecutive days with 5% OVA and AHR was assessed 24 h after the last challenge. we examined the lung histology, airway hyper sensitivity, total inflammatory cell count in bronchoaveloar lavage fluid(BALF), Th2-associated cytokines production and IgE production. Results : ES potently inhibited the lung damage and the development of Penh. ES also reduced the number of BAL cells during OVA-induced allergic asthma. Furthermore, ES inhibited cytokines production such as IL-4, IL-13 productions, and IgE level of serum. Conclusion : These results suggest that ES may inhibit the production of IL-4, IL-13, IgE and infiltration of inflammatory cell and be beneficial oriental medicine for allergic asthma.

• 한방안이비인후피부과학회지
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• 제27권3호
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• pp.96-105
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• 2014

Objective : Glycyrrhiza uralensis Fisch (GUF) has been used as remedy of allergic diseases for a long time in Korea. In the present study, we investigated the anti-allergic effects of GUF on experimental allergic asthma mouse model using ovalbumin (OVA). Methods : BALB/c mice were sensitized and challenged with 100 ug of OVA and 1 mg of aluminum potassium sulfate of 0.2 ml phosphate-buffered saline (PBS) intraperitoneally on day 1 and 15. Mice were challenged on 3 consecutive days with 5% OVA and AHR was assessed 24 hrs after the last challenge. We examined total inflammatory cell number in bronchoaveloar lavage fluid (BALF), Th2-associated cytokine productions and lung histology. Results : GUF potently inhibited the development of airway hypersensitivity and also reduced the number of BAL cells during OVA-induced allergic asthma. GUF also inhibited cytokine productions such as IL-4, IL-13 in lung tissue. Furthermore, GUF treatment inhibited allergic airway inflammation. Conclusion : These results suggest that GUF may inhibit the production of IL-4, IL-13 and infiltration of inflammatory cell and be beneficial oriental medicine for allergic asthma.

• IMMUNE NETWORK
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• 제16권3호
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• pp.165-175
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• 2016

Ambroxol is used in COPD and asthma to increase mucociliary clearance and regulate surfactant levels, perhaps through anti-oxidant and anti-inflammatory activities. To determine the role and effect of ambroxol in an experimental model of asthma, BALB/c mice were sensitized to ovalbumin (OVA) followed by 3 days of challenge. Airway hyperresponsiveness (AHR), lung cell composition and histology, and cytokine and protein carbonyl levels in bronchoalveolar lavage (BAL) fluid were determined. Ambroxol was administered either before the first OVA challenge or was begun after the last allergen challenge. Cytokine production levels from lung mononuclear cells (Lung MNCs) or alveolar macrophages (AM) were also determined. Administration of ambroxol prior to challenge suppressed AHR, airway eosinophilia, goblet cell metaplasia, and reduced inflammation in subepithelial regions. When given after challenge, AHR was suppressed but without effects on eosinophil numbers. Levels of IL-5 and IL-13 in BAL fluid were decreased when the drug was given prior to challenge; when given after challenge, increased levels of IL-10 and IL-12 were detected. Decreased levels of protein carbonyls were detected in BAL fluid following ambroxol treatment after challenge. In vitro, ambroxol increased levels of IL-10, IFN-γ, and IL-12 from Lung MNCs and AM, whereas IL-4, IL-5, and IL-13 production was not altered. Taken together, ambroxol was effective in preventing AHR and airway inflammation through upregulation of Th1 cytokines and protection from oxidative stress in the airways.