• Biomolecules & Therapeutics
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• v.32 no.4
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• pp.460-466
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• 2024

Asthma is characterized by chronic inflammation and respiratory tract remodeling. Peroxisome proliferator-activated receptors (PPARs) play important roles in the pathogenesis and regulation of chronic inflammatory processes in asthma. The role of PPARγ has been studied using synthetic PPARγ agonists in patients with asthma. However, involvement of PPARα/δ has not been studied in asthma. In the present study, we investigated if elafibranor, a PPARα/δ dual agonist, can modulate ovalbumin (OVA)-induced allergic asthma, which is a potential drug candidate for non-alcoholic fatty liver in obese patients. Elafibranor suppresses antigen-induced degranulation in RBL-2H3 mast cells without inducing cytotoxicity in vitro. In mice with OVA-induced allergic asthma, the administration of elafibranor suppressed OVA-induced airway hyper-responsiveness at a dose of 10 mg/kg. Elafibranor also suppressed the OVA-induced increase in immune cells and pro-inflammatory cytokine production in the bronchoalveolar lavage fluid (BALF). Histological studies suggested that elafibranor suppressed OVA-induced lung inflammation and mucin hyper-production in the bronchial airways. In addition, elafibranor suppressed OVA-induced increases in serum immunoglobulin E and IL-13 levels in BALF. Conversely, the present study suggests that elafibranor has the potential for use in patients with allergic asthma.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.24 no.1
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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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• v.32 no.4
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• pp.451-459
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• 2024

Apoptosis signal-regulating kinase 1 (ASK1) is an upstream signaling molecule in oxidative stress-induced responses. Because oxidative stress is involved in asthma pathogenesis, ASK1 gene deficiency was investigated in animal models of allergic asthma. However, there is no study to investigate whether ASK1 inhibitors could be applied for asthma to date. Selonsertib, a potent and selective ASK1 inhibitor, was applied to BALB/c mice of an ovalbumin (OVA)-induced allergic asthma model. Selonsertib suppressed antigen-induced degranulation of RBL-2H3 mast cells in a concentration-dependent manner. The administration of selonsertib both before OVA sensitization and OVA challenge significantly reduced airway hyperresponsiveness, and suppressed eosinophil numbers and inflammatory cytokine levels in the bronchoalveolar lavage fluid. Histopathologic examination elucidated less inflammatory responses and reduced mucin-producing cells around the peribronchial regions of the lungs. Selonsertib also suppressed the IgE levels in serum and the protein levels of IL-13 in the bronchoalveolar lavage fluid. These results suggest that selonsertib may ameliorate allergic asthma by suppressing immune responses and be applicable to allergic asthma.

• The Journal of Internal Korean Medicine
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• v.29 no.2
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• pp.456-468
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• 2008

Objective : The purpose of this study was to investigate the effects of Gamisagunja-tang(GS) on the airway hyper-reactivity (AHR), cytokine production and T cell activation during the ovalbumin (OVA)-induced allergic asthma in mice. Materials and Methods : BALB/c mice were sensitized and challenged with 100 mg of OVA and 1 mg of aluminum potassium sulfate intraperitoneally on days 1 and 7. On day 14, mice were challenged on 3 consecutive days with 5% OVA. AHR and bronchoalveolar fluid (BALF), total inflammatory cell count and the production of cytokines were measured. Results : GS significantly suppressed the infiltration of inflammatory cells in the lung tissue and AHR. GS significantly down regulated the production of IL-4, IL-5 and increases of $INF-{\gamma}$ in BALF. GS reduced the population of eosinophils from lung and spleen in OVA-induced allergic asthma. GS reduced the population of $CD4^{+}$ $CD69^{+}$ $CD25^{-}$ T cells in OVA-induced allergic asthma Conclusion : These results suggest that GS may inhibit the production of IL-4, IL-5 and infiltration of eosinophils and be beneficial oriental medicine for allergic asthma.

• The Korean Journal of Food And Nutrition
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• v.36 no.3
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• pp.172-184
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• 2023

The objective of this study was to determine the efficacy of a natural product of cherry tree (Prunus serrulata var. spontanea: PS) as a test substance for improving cytokine and ovalbumin-specific IgE using an ovalbumin-induced asthma disease model of 5-week-old male BALB/c mice. Lung tissue pathology was analyzed to confirm anti-inflammatory and asthmatic effects. As a result of examining the effect on changes in inflammatory cells in bronchoalveolar lavage fluid in an ovalbumin-induced asthma disease model by administering the PS sample, total cells, eosinophil, neutrophil, lymphocyte, and monocytes were significantly decreased. Concentrations of cytokine-based TNF-alpha and IL-4 and immunoglobulin E in serum were significantly increased in the asthma-inducing negative control group than in the normal group. However, high concentrations of PS decreased them. In histopathological examination of the lung tissue, it was confirmed that inflammatory cells infiltrated around the alveoli and bronchioles were increased in ovalbumin-induced asthma disease model. After administration of cherry tree extract, bronchiolar morphological changes such as mucosal thickening were slightly improved. From the above results, it was confirmed that extract of cherry tree significantly reduced inflammation expression and tissue damage in alveolar tissues. It was also confirmed that the cherry tree extract had an excellent efficacy in improving asthma inflammation.

• The Korea Journal of Herbology
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• v.30 no.1
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• pp.25-32
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• 2015

Objectives : In this study, we investigated the effect of Cassia obtusifolia Linne (Cassiae Semen; CS) extract on ovalbumin (OVA)-induced allergic asthma in mice. Methods : CR was extracted with 70% ethanol. For in vitro study, HMC-1, human mast cells were treated with CS extract at 0.2 and $0.5mg/m{\ell}$ for 1 h, and then stimulated with compound (C) 48/80 for 30 min. Primary spleenocytes were isolated from the spleen of mice, treated with CS extract for 1 h, and then stimulated with ConA for 24 h. For in vivo study, mice were sensitized at day 0, 7 and 14 with 0.2% OVA and then airway challenged using neublizer at day 21, 23, 25, and 27 to induced allergic asthma. CS extract at doses of 100 and 300 mg/kg body weight was orally administered during OVA challenge once per a day. The levels of allergic mediators such as histamine, OVA-specific IgE, IL-4, and $IFN-{\gamma}$ were measured in the sera of mice or culture supernatants by EIA and ELISA, respectively. The expression of IL-4 and $IFN-{\gamma}$ gene was determined by RT-PCR. The histopathological change of lung tissues was observed with hematoxylin and eosin (H&E) and Periodic acid Schiff (PAS) staining. Results : The treatment of CS extract in HMC-1 cells significantly inhibited C48/80-induced degranulation, and histamine release. The treatment of CS extract in spleenocytes suppressed the expression of IL-4 and $IFN-{\gamma}$ mRNA. The administration of CS extract in OVA-induced asthmatic mice significantly decreased the levels of OVA-specific IgE, and IL-4 in a dose-dependent manner with OVA-control group. In addition, CS extract inhibited the infiltration of inflammatory cells and bronchiolar damage with epithelial thickening in lung tissues of OVA-induced asthma mice, and also mucin accumulation. Conclusions : These results indicate that CS extract prevents asthmatic damage through regulating the allergic immune response.

• The Korea Journal of Herbology
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• v.29 no.4
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• pp.1-8
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• 2014

Objectives : The root bark of Morus alba L. (Mori Cortex Radidus; MCR) has been traditionally used to reduce heat from the lungs, soothe asthma, and edema and to promote urination. In this study, we investigated the effect of MCR ethanol extract on ovalbumin (OVA)-induced allergic asthma in mice. Methods : Mice were sensitized at day 0, 7 and 14 with 0.2% OVA and then airway challenged at day 21, 23, 25, 27 and 29 to induce allergic asthma. MCR extracts at doses of 50 and 100 mg/kg body weight (bw) were orally administered during OVA challenge once per a day. The levels of allergic mediators such as histamine, OVA-specific IgE, IFN-${\gamma}$ and IL-4 were measured in the sera of mice by ELISA. The histopathological change of lung tissues was observed with hematoxylin and eosin (H&E) staining. Results : MCR extract significantly decreased not only the serum levels of histamine, OVA-specific IgE, and IL-4 compared with those of OVA control group, but significantly increased the serum level of IFN-${\gamma}$. In H&E staining, MCR extract inhibited the infiltration of inflammatory cells and bronchiolar damage with epithelial thickening in lung tissues of OVA-induced asthma mice. Conclusions : These results indicate that MCR extract inhibits lung damage by asthma through regulating the allergic immune response, suggesting that MCR may be used as a useful agent for the treatment of allergic asthma.

• Journal of Life Science
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• v.22 no.3
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• pp.298-305
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• 2012

The general term flavonoids is often used to categorize a family of natural compounds that are highly abundant in all higher plants, and which in recent years have attracted scientific interest as therapeutics. Lutein is a xanthophyll and one of 600 known naturally occurring carotenoids. It is found in green vegetables such as spinach and kale, and has been demonstrated to exert anti-inflammatory activities. However, its anti-allergic effect in the Th1/Th2 immune response is poorly understood. In this study, we attempt to determine whether lutein regulates inflammatory mediators in an ovalbumin (OVA)-induced murine asthma model. To address this, mice were sensitized and challenged with OVA, and then treated with lutein before the last OVA challenge. Administration of lutein significantly suppressed the OVA-induced airway hyper-responsiveness. It also resulted in a significant alleviation of the infiltration of inflammatory cells into the bronchoalveolar lavage. Additionally, lutein attenuated the increased expression of Th2 responses in OVA-challenged mice. These results demonstrate that lutein is a potent inhibitor that reduces Th2 immune responses. Furthermore, they show that the immunopharmacological function is mediated by a pathway that involves and is regulated by Th2 immune response.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.20 no.3
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• pp.107-117
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• 2007

Objective : Kumsoouyukkun-joen extract(KSE) has been used treating asthma for a long time in korea. In the present study, I examined the effects of KSE on the ovalbumin(OVA)-induced airway hyper-reactivity(AHR). Methods : To examine the effects of KSE on asthma, mice were sensitized with $100{\mu}g$ of OVA and 1 mg of aluminum potassium sulfate(Alum; Sigma)intraperitoneally on day 0 and 7. On day 14, mice were challenged on 3 consecutive days with 5% OVA and AHR was assessed 24 hrs after the last challenge. To examine severity of AHR, I examined eosinophil population and cytokine production in bronchoaveloar lavage fluid(BALF) and stained with hematoxylin and eosin in lung and also measured enhanced pause(Penh) in AHR from mice. Results and Conclusion : KSE potently inhibited the development of Penh and also reduced the number of eosinophil during OVA-induced AHR. KSE also inhibited cytokines production such as IL-4, IL-5 in BALF. Furthermore, KSE inhibited percentage of eosinophil in BALF. These results suggest that KSE may be beneficial oriental medicine for AHR.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.5
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• pp.1159-1165
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• 2006

This study was done to investigate the effects of Gamisojaganggi-tang(GSGT) on immunopathologic changes in OVA-induced asthma model of mice. Pathologic indicators associated with this immune disease, which include cytokines, the number of immune-cells, immunoglobin E (IgE), were examined, and histological changes of bronchial tissues were also examined. The administration of GSGT significantly reduced the lung weight compared with control mice of OVA-induced asthma model. The administration of GSGT significantly reduced the number of total cells in BALF compared with control mice of OVA-induced asthma model. The administration of GSGT significantly reduced the number of eosinophil in BALF compared with control mice of OVA-induced asthma model. The administration of GSGT insignificantly increased the number of monocyte in BALF compared with control mice of OVA-induced asthma model. The administration of GSGT significantly reduced the number of lymphocyte in BAL compared with control mice of OVA-induced asthma model. The administration of GSGT significantly reduced the gene expression of eotaxin in lung tissue compared with control mice of OVA-induced asthma model. The administration of GSGT insignificantly reduced the IL-4 and IL-5 production in BALF compared with control mice of OVA-induced asthma model. The administration of GSGT insignificantly reduced the levels of total IgE and ovalbumin-specific IgE in BALF. The administration of GSGT significantly reduced the levels of ovalbumin-specific IgE whereas the serum levels of total IgE were insignificantly reduced compared with control mice of OVA-induced asthma model. The administration of GSGT moderately reduced bronchial alveolar narrowing, bronchiovascular edema and increase in the size of alveolar space, which shown in control mice of OVA-induced asthma model, in a dose dependent manner. Furthermore, GSGT reduced invasion of inflammatory cells, and proliferation of smooth muscle cells in bronchial tissue. These results suggested that GSGT has suppressive effects on pathologic changes associated with disease progression in asthma through the modulation of immune system. GSGT has potential to use as an anti-asthmatic agents.