• Archives of Pharmacal Research
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• 제28권12호
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• pp.1350-1357
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• 2005

Nuclear factor kappa B (NF-$\kappa$B) regulates the expression of multiple cytokines, chemokines, and cell adhesion molecules that are involved in the pathogenesis of asthma. We investigated the anti-asthmatic effects and the mechanism of action of DA-9201, an extract of the black rice, in a mouse model of asthma. Mice immunized with ovalbumin (OVA) were administered with DA-9201 (30, 100 or 300 mg/kg) or dexamethasone (DEXA, 3 mg/kg) for 2 weeks and challenged with aerosolized OVA during the last 3 days. Anti-asthmatic effects were assessed by means of enhanced pauses, level of total lgE and Th2 cytokines in plasma or bronchoalveolar lavage fluid (BALF), the percentage of eosinophils in BALF, and histopathological examination. The expression of NF-$\kappa$B in nuclear and cytoplasmic fraction and its DNA-binding activity in lung tissues were analyzed by means of Western blotting and electrophoretic gel mobility shift assay (EMSA), respectively. DA-9201 significantly reduced airway hyperrespon-siveness (AHR), total lgE level in plasma and BALF, IL-4, IL-5, and IL-13 levels in BALF, and the percentage of eosinophils in BALF. Tissue inflammation was significantly improved by DA­9201 treatment. In addition, DA-9201 dramatically suppressed the expression of NF-$\kappa$B and its DNA-binding activity. These results suggest that DA-9201 may be useful for the treatment of asthma and its efficacy is related to suppression of NF-$\kappa$B pathway.

• 대한한의학회지
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• 제24권1호
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• pp.74-83
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• 2003

Background : Production of cytokines by bronchial epithelial cells may contribute to the local accumulation of inflammatory cells in patients with bronchial asthma. In many recent studies, molecular biological methods have been used to investigate the role of cytokines in pathogenesis and new therapeutic targets of asthma. Objective : We aimed to identify the dose-dependent inhibitory effects of Socheongryong-tang and Socheongryong-tang plus Sasam (Adenophorae Radix) on the mRNA expressions of Interleukin (IL)-6, IL-8 and granulocyte macrophage colony stimulating factor (GM-CSF) involved in the asthma model. Materials and Methods : In this study, BEAS-2B cell lines, human epithelial cells, were used. These cells were stimulated by tumor necrosis factor $(TNF)-{\alpha},{\;}IL-1{\beta}$ and histamine for artificial inflammatory expression. ${\beta}-actin$ messenger RNA (mRNA) was used for the internal standard. After each 24 hours of the Socheongryong-tang (小靑龍湯) and Socheongryong-tang plus Sasam (小靑 龍湯加沙蔘) treatment, total cellular RNAs were collected by applying RNAzol directly to the living cells. Then the transcriptional activities of IL-6, IL-8 and GM-CSF were measured by RT-PCR with electrophoresis. Results : In the Socheongryong-tang (小靑龍湯) study, the mRNA expressions of IL-6, IL-8 and GM-CSF were significantly inhibited compared to that of the control group (p<0.05). In the Socheongryong-tang plus Sasam (小靑龍湯加沙蔘) study, the mRNA expressions of IL-6, IL-8 and GM-CSF were significantly inhibited compared to that of the control group (p<0.05). Conclusions : This study shows that Socheongryong-tang (小靑龍湯) and Socheongryong-tang plus Sasam (小靑龍湯加沙蔘) have dose-dependent inhibitory effects on the mRNA expressions of IL-6, IL-8 and GM-CSF in human epithelial cells, so these herbal medicines may inhibit the inflammatory process of asthma. Advanced studies are required to investigate the mechanisms of inhibition by herbal medicine in the asthma model.

• Journal of Pharmaceutical Investigation
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• 제41권6호
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• pp.355-362
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• 2011

This work was performed to investigate the protective effect of ethanol extract (AEx) from acorn (Quercus acutissima CARR.) against allergic mediated responses in asthma model cells and mice. The AEx inhibited antigen-stimulated cytokine production such as interleukin (IL)-4, IL-13 and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and AEx also inhibited intracellular reactive oxygen species (ROS) generation against IgE-mediated allergic response in rat basophilic leukaemia RBL-2H3 cells. The ovalbumin (OVA)-sensitized mice were orally administered with AEx (100 or 300 mg/kg) and authentic tannic acid (75 mg/kg) every day for 15 days. Increased TNF-${\alpha}$ production by OVA-sensitization/challenge was significantly reduced by administration of AEx. The serum triglyceride levels of asthma mice were significantly reduced after feeding for 15 days with tannic acid or AEx. The mice fed with tannic acid or AEx also exhibited a significant reduction in body weights compared to those of asthma control group. The AEx increased the heme oxygenase (HO)-1 mRNA expression in the asthma model mice and showed DPPH radical scavenging activity. These results indicate that AEx protects against IgEmediated allergic and OVA-induced asthmatic responses via direct and indirect antioxidant activities. Reduced triglyceride and body weights may provide additional protective benefits of AEx on allergic asthma.

• 동의생리병리학회지
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• 제20권6호
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• pp.1593-1597
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• 2006

We hope to evaluate the effects of Gami-Choakwiyeum (GCKY) on the PPAR-${\gamma}$’ in the OVA induced asthma mouse model. Female BALB/c mice, 8 weeks of age and free of murine specific pathogens were used. Mice were sensitized by intraperitoneal injection of OVA emulsified in aluminum hydroxide in a total volume of 200 ${\mu}{\ell}$ on one day and 14 days. On 21, 22, and 23 days after the initial intraperitoneal injection of OVA, the mice were challenged using an ultrasonic nebulizer. GCKY was administered 7 times by oral gavage at 24 hour intervals fromdays 19 after intraperitoneal injection of OVA. Bronchoalveolar lavage was perfromed 72 hours after the last challenge, and total cell numbers in the BAL fluid were counted. Also, the level of PPAR-${\gamma}$ of normal and OVA-induced asthma moused with/without administration of GCKY were measured by Western blot analysis. For the histologic examination, the specimens were stained with hematoxylin 2 and eosin-Y.(H & E). Numbers of total cells were increased significantly at 72 h after OVA inhalation compared with numbers of total cells in the normal and the administration of GCKY. Especially, the increased numbers of eosinophils in BAL fluids after OVA inhalation were significantly increased. However, the numbers of eosinophils reduced by the administration of GCKY. Western blot analysis revealed that PPAR-${\gamma}$ levels in nuclear level were increased slightly after OVA inhalation compared with the levels in the normal group. After the administration of GCKY, PPAR-${\gamma}$ levels in cytosolic and nuclear levels at 72 h after OVA inhalation were markedly increased. On pathologic examination, there were many acute inflammatory cells around the alveoli, bronchioles, and airway lumen of mice with OVA-induced asthma compared with inflammatory cells in the normal group. However, acute inflammatory cells around alveoli, bronchioles, and airway lumen markedly decreased after administration of GCKY, GCKY can increase a PPAR-${\gamma}$ level and could be an effective treatment in asthma patients through the PPAR-${\gamma}$ mechanism for bronchial asthma.

• The Korean Journal of Physiology and Pharmacology
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• 제25권6호
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• pp.555-564
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• 2021

We investigated the effects of naringenin and morin on IL-5 and ROS production in PMA+ionomycin-treated EL-4 cells with the corroboration of their antioxidant and anti-inflammatory properties using an asthma-induced mouse model. The EL-4 cell line was used to study the outcomes of naringenin or morin, followed by cell viability studies. Western blot analysis and ELISA test were used to determine Th2 mediated cytokines. In vivo studies were carried out on BALB/c mice to induce allergic asthma using ovalbumin administered intraperitoneally. Intracellular ROS was determined using 2',7'-dichlorodihydrofluorescein diacetate, followed by serum enzymatic (AST and ALT) estimations and inflammatory cell count in the bronchoalveolar lavage fluid (BALF) and lung tissues. Histopathological studies were conducted to examine lung tissue-stained architecture. Our findings suggested that naringenin and morin significantly suppressed IL-5 and ROS production via various pathways. Interestingly, by reducing NFAT activity, naringenin and morin stimulated HO-1 expression, thereby suppressing IL-5 secretion due to regulating the transcription factor Nrf2 via P13/Akt or ERK/JNK signalling pathways in EL-4 cells, demonstrating the involvement of HO-1 expression in inhibiting asthmatic inflammation. The increased inflammatory cells in the BALF were substantially decreased by both naringenin and morin, followed by inhibition in the elevated Th-2 cytokines levels. The TNF-α protein levels in an allergic asthma mouse model were significantly reduced by suppressing Akt phosphorylation and eosinophil formation. Recent findings confirmed that naringenin and morin possess the potential to control asthma-related immune responses through antioxidant and anti-inflammatory properties, indicating potential therapeutic agents or functional foods.

• 한국약용작물학회지
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• 제23권3호
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• pp.237-244
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• 2015

In this study, essential oils were extracted from the leaf of Chamaecyparis obtusa (CLEO), indigenous to Korea, CLEO constituents were analysed, and the effects of CLEO on airway hyperresponsiveness (AHR) and airway inflammation (AI) were investigated in Ovalbumin (OVA)-induced asthma mouse model. Terpenoid components among identified CLEO constituents made up more than 80%. The CLEO-treated group in comparison to the control group showed reduced AHR, the decrease of eosinophil number in the bronchoalveolar lavage fluid (BALF), reduced specific anti-OVA IgE level in the serum, and a significant reduction in Th2 cytokines levels in the BALF with concentration. We concluded that CLEO have an alleviating effect on asthma-like symptoms such as AHR and AI. Further studies about antiasthmatic effect are necessary on the focus of single component of CLEO.

• Tuberculosis and Respiratory Diseases
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• 제81권1호
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• pp.80-87
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• 2018

Background: Asthma is a disease of chronic airway inflammation with heterogeneous features. Neutrophilic asthma is corticosteroid-insensitive asthma related to absence or suppression of $T_H2$ process and increased $T_H1$ and/or $T_H17$ process. Macrolides are immunomodulatory drug that reduce airway inflammation, but their role in asthma is not fully known. The purpose of this study was to evaluate the role of macrolides in neutrophilic asthma and compare their effects with those of corticosteroids. Methods: C57BL/6 female mice were sensitized with ovalbumin (OVA) and lipopolysaccharides (LPS). Clarithromycin (CAM) and/or dexamethasone (DXM) were administered at days 14, 15, 21, 22, and 23. At day 24, the mice were sacrificed. Results: Airway resistance in the OVA+LPS exposed mice was elevated but was more attenuated after treatment with CAM+DXM compared with the monotherapy group (p<0.05 and p<0.01). In bronchoalveolar lavage fluid study, total cells and neutrophil counts in OVA+LPS mice were elevated but decreased after CAM+DXM treatment. In hematoxylin and eosin stain, the CAM+DXM-treated group showed less inflammation additively than the monotherapy group. There was less total protein, interleukin 17 (IL-17), interferon ${\gamma}$, and tumor necrosis factor ${\alpha}$ in the CAM+DXM group than in the monotherapy group (p<0.001, p<0.05, and p<0.001). More histone deacetylase 2 (HDAC2) activity was recovered in the DXM and CAM+DXM challenged groups than in the control group (p<0.05). Conclusion: Decreased IL-17 and recovered relative HDAC2 activity correlated with airway resistance and inflammation in a neutrophilic asthma mouse model. This result suggests macrolides as a potential corticosteroid-sparing agent in neutrophilic asthma.

• Journal of Preventive Medicine and Public Health
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• 제30권2호
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• pp.428-436
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• 1997

Objectives : The purpose of this paper is to estimate the completeness of the Korean Medical Insurance Data in childhood asthma. Methods : Capture-recapture method was used to estimate the prevalence of childhood asthma and case ascertainment rate(completeness) of Korean Medical Insurance Data using two source model, 'Korean Medical Insurance Committee Data (KMICD)' and 'Nationwide Study of Asthma and Allergies in Korean Children'. The asthma cases were restricted to those who were born from 1981 to 1989 and were identified by their Resident Register Number. Asthma cases in Korean Medical Insurance Data were defined as cases coded by ICD-9 493 and ICD-10 J45. In 'Nationwide Study of Asthma and Allergies in Korean Children', asthma cases were defined as the children who had been diagnosed asthma and had experienced symptoms of asthma during the past 12 months. The defined cases in two data sources were matched by 13 digits Resident Register Number. The numbers of matched patients in two data sources were 245 of 32,825 eligible total subjects. Chapman and Wittes' nearly unbiased estimation was used for capture-recapture analysis of two data sources. Results : Observed prevalence rate of childhood asthma was 5.3% and estimated prevalence rate by capture-recapture analysis was 11.6%. The highest prevalence rate was observed in 6-7 age group and the older the rate decreased. The completeness (the proportion of cases ascertained by KMICD to the total observed cases by two data sources) was 20.6%, and ranged form 10.8% to 28.8% by area. Conclusions : Invalid diagnosis of cases might overestimate the prevalence of child-hood asthma and might underestimate the completeness of Korean Medical Insurance Committee Data in this study.

• 생명과학회지
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• 제17권3호통권83호
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• pp.396-401
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• 2007

천식이 유발된 Balb/c마우스와 동일한 조건의 IL-10 KO 마우스에 천식의 원인으로 알려진 DEP와 지하철역내에서 채집한 PM (10 ${\mu}g/m^3$)을 inhalation chamber,에 넣고 하루 4시간씩 흡입시킨 후 시료들을 채취하여 ICAM-1, VCAM-1의발현을 살펴 천식증상의 악화에 DEP와 PM이 어데한 영향을 미치는지 확인하였다. 본 실험의 결과 천식이 유발된 일반 Balb/c 마우스에 있어서는 DEP와 PM의 노출에 의하여 ICAM-1 및 VCAM-1의 발현이 세기관지 주위 조직들에서 미약하게 증가하였다. 그러나 IL-10 KO 마우스의 경우 DEP와 PM을 노출시켰을 때 ICAM-1 및 VCAM-1의 발현이 아주 강하게 증가하였다. 따라서, 본 결과는 IL-10에 대한 항체요법이 천식증상의 완화에 쓰일 수 있는 가능성을 암시하며, 한편 자동차 배기가스와 지하철 미세분진의 발생을 예방할 경우 천식과 관련한 세기관지의 염증을 완화시킬 수 있음을 간접적으로 증명한 것이라 할 수 있다.

• 동의생리병리학회지
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• 제16권6호
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• pp.1217-1222
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• 2002

This study was aimed to find out Kami-Chungsangboha-tang's effects on allergic asthma using Egg-White Implant(EWI) method model recommended by Siqueira et al. Kami-Chungsangboha-tang has widely been prescribed and used in Oriental Medicine for controlling and curing of the symptoms of Asthma(dyspnea, wheezing, cough, sputum, chest discomfort). The Previous studies have demonstrated that Kami-Chungsangboha-tang had analgesic, sedative, anticonvulsive and antihistamine effects. But it was uncertain whether Kami-Chungsangboha-tang could inhibit the allergic reaction, so alleviate the symptoms of allergic asthma. With such aim, the respiratory patterns and eosinophil infiltration in the tracheal mucosa of rats with experimentally induced allergic asthma (using EWI method) were mainly observed. The results are as follows ; 1. Kami-Chungsangboha-tang decreased the number of malformed respiration with respect to control group (p<0.02). 2. Kami-Chungsangboha-tang decreased the number of eosinophils infiltrated in tracheal mucosa with respect to control group (p<0.05). Depending upon above results, it is considered that Kami-Chungsangboha-tang has the inhibitory effects on the process of allergic asthma and suggested that it could be used in relieving patients of the symptoms caused by allergic asthma.