• Title/Summary/Keyword: Asthma animal models

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Selonsertib, an ASK1 Inhibitor, Ameliorates Ovalbumin-Induced Allergic Asthma during Challenge and Sensitization Periods

  • So-Young Han;Dong-Soon Im
    • 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.

Improvement of Bronchial Immune Hypersensitivity Reaction by Extracts from Chrysanthemum morifolium and Scutellaria baicalensis

  • Kyoung won Cho;Sung Sun Park;Hak Joo Choi
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2020.08a
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    • pp.78-78
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    • 2020
  • This study aimed to discover functional materials derived from resources, which can improve the troublesome symptoms of a bronchus by improving bronchial hyperresponsiveness as air pollution in Korea caused by fine dust and yellow dust is getting worse. Of natural resources grown naturally in Korea, Chrysanthemum morifolium(CM), and Scutellaria baicalensis(SB) have been used as a safe raw material for drinking or medicine for a long time, and it has been found that a combination of CS73 can improve bronchial health function in experimental animal models. Analysis of serum of animal models with asthma induced by ovalbumin (chicken egg albumin) and analysis of cytokine production in BALF (Bronchoalveolar lavage fluid) showed that inflammatory indices IL-1β, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17A, IL-17F, and IL-17E were significantly reduced and that respective production of IL-2 and IFN-γ was significantly increased in the group taking extracts from CS73 when compared with the control group. These results suggested that the combination of CS73 could be used as a natural treatment for asthma. In addition, in the animal models that the combination of CS73 significantly decreased the respective production of IgE, histamine and TSLP when compared with the control group. In experimental models, the ratio of Chrysanthemum morifolium to Scutellaria baicalensis of 7 : 3 had more excellent effect than other combined experimental groups, which suggests that the above combination can be developed as a natural treatment for asthma and is valuable as a pharmaceutical composition with an effect of improving bronchial health, capable of contributing to the public health threatened by fine dust.

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Neural Mechanism in Bronchial Asthma (기관지천식에서의 신경적 기전)

  • Choi, Byoung-Whui
    • Tuberculosis and Respiratory Diseases
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    • v.41 no.2
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    • pp.73-86
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    • 1994
  • In addition to classic cholinergic and adrenergic pathways, the existence of a third division of autonomic control in the human airways has been proved. It is called a nonadrenergic noncholinergic(NANC) nervous system, and difficult to study in the absence of specific blockers. Neuropeptides are certainly suggested to be transmitters of this NANC nervous system. It is very frustrating to understand the pathophysiologic role of these peptides in the absence of any specific antagonists. However, further studies of neuropeptides might eventually lead to novel forms of treatment for bronchial asthma. Another study of the interaction between different components of the autonomic nervous system, either in ganglionic neurotransmission or by presynaptic modulation of neurotransmitters at the end-organ will elute neural control in airway disease, particularly in asthma. Studies of how autonomic control may be disordered in airway disease should lead to improvements in clinical management. Epithelial damage due to airway inflammation in asthma may induce bronchial hyperresponsiveness. Axon reflex mechanism is one of possible mechanisms in bronchial hyperresponsiveness. Epithelial damage may expose sensory nerve terminals and C-fiber nrve endings are stimulated by inflammatory mediators. Bi-directional communication between the nerves and mast cells may have important roles in allergic process. The psychological factors and conditioning of allergic reactions is suggested that mast cell activation might be partly regulated by the central nervous system via the peripheral nerves. Studies in animal models, in huamn airways in vitro and in patients with airway disease will uncover the interaction between allergic disease processes and psychologic factors or neural mechainsms.

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Effect of respiratory syncytial virus infection on regulated on activation, normal T-cells expressed and secreted production in a murine model of asthma

  • Ju, Yanghua;Choi, Seung-Jun;Lee, Hui-Su;Kim, Hyun-Sook;Won, Sul-Mui;Chun, Yoon-Hong;Yoon, Jong-Seo;Kim, Hyun-Hee;Lee, Joon-Sung
    • Clinical and Experimental Pediatrics
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    • v.54 no.11
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    • pp.456-462
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    • 2011
  • Purpose: Synthesis of regulated on activation, normal T-cells expressed and secreted (RANTES) in the airway has previously been shown to be elevated after respiratory syncytial virus (RSV) infection. However, since few studies have examined whether RSV-infected asthma patients express a higher level of RANTES than do normal individuals, we used a murine model of asthma to address this question. Methods: We prepared Dermatophagoides farinae-sensitized mice as an asthma model, and then infected them with RSV and analyzed the changes in airway responsiveness and the cell populations and cytokine levels of bronchoalveolar lavage fluid. Results: RANTES synthesis increased in response to RSV infection in both control mice and in asthma model (D. farinae) mice. However, there was no significant difference in the amount of RANTES produced following RSV infection between control and D. farinae mice. RSV infection affected neither interferon-${\gamma}$ synthesis nor airway responsiveness in either control or D. farinae mice. Conclusion: RSV infection did not induce more RANTES in a murine model of asthma than in control mice.

Review on the Effects of Herbal Medicine on Respiratory Diseases in In Vivo Particulate Matter Models (미세먼지 in vivo 모델에서 호흡기 질환에 대한 한약의 효과에 관한 연구 동향 분석)

  • Seong-cheon Woo;Su-won Lee;Yang-chun Park
    • The Journal of Internal Korean Medicine
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    • v.44 no.3
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    • pp.418-438
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    • 2023
  • Objective: This study was conducted to review the effects of herbal medicine on respiratory diseases induced by the treatment of particulate matter in in vivo animal models. Methods: Literature searches were performed in seven databases (Pubmed, Embase, Cochrane Library, KISS, KTKP, OASIS, and ScienceON). After the searched studies were screened based on the inclusion/exclusion criteria, the publication date, origin, used animals, induction of particulate matter models, herbal medicine used for intervention, study design, outcome measure, and results of studies were analyzed. Results: Among a total of 972 studies primarily searched, 34 studies were finally included in our study. Of this number, 29 studies induced animal models by using only particulate matter, and 5 studies induced animal models with respiratory diseases, such as asthma and chronic obstructive pulmonary disease, by using particulate matter and other materials. In the selected studies, the treatments of herbal medicine in particulate matter models suppressed oxidative stress and inflammation in lung tissue, bronchoalveolar lavage fluid, and blood as well as lung injury in histological analysis. Conclusion: The results of this study suggest that herbal medicine is effective in treating respiratory diseases induced by particulate matter. These results are also expected to be useful data for designing further studies. However, more systematically designed in vivo studies related to particulate matter are needed.

Water-extract of Helianthus annuus Seed Exhibits Potent Anti-asthma Activity In Vitro and In Vivo (해바라기씨 추출물의 천식 완화 효과)

  • Heo Jin-Chul;Park Ja-Young;Woo Sang-Uk;Chung Shin-Kyo;Jeong Kyu-Shick;Lee Jin-Man;Ma Jin-Yeol;Lee Sang-Han
    • Food Science and Preservation
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    • v.13 no.4
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    • pp.495-500
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    • 2006
  • In order to investigate whether antioxidant biomaterials inhibits IL-4 and/or IL-13 expression in vitro and in vivo, we carried out antioxidant assays by enzyme or cell-based assays with Helianthus annuus extract. Antioxidant assays include DPPH, FRAP, hydroxyl radical assays. Helianthus annuus extract exhibited SOD scavenging activity, and had different patterns by each solvent extracted reaction. DW extract inhibited oxidative stress by $H_2O_2$ that induced apoptosis. We measured $CD4^+$ cell and IL-/13 cytokine expression in a classical mouse animal model. The result show that Helianthus annuus extract showed strung inhibition of immune response in the lung. These result suggest that Helianthus annuus extract can reduce inflammation induced by n mouse asthma model.

Early Bronchoconstriction After Allergen Challenge of Nonanesthetized Guinea Pigs (Ovalbumin으로 감작된 기니픽에서 Allergen 흡입으로 인한 즉시형 기관지 수축반응에 대한 비침습적 측정)

  • Kim, Je-Hyeong;Shim, Jae-Jeong;Lee, Sung-Yong;Kwon, Young-Hwan;Lee, So-Ra;Lee, Sang-Youb;Cho, Jae-Youn;In, Kwang-Ho;Yoo, Se-Hwa;Kang, Kyung-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.1
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    • pp.99-106
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    • 1998
  • Background: Bronchial asthma is a complex disease, which is characterized by spontaneous exacerbations of airway obstruction and persistent bronchial hyperresponsiveness. Animal models have fallen short of reproducing the human disease, particularly in mimicking the spontaneous and persistent airflow obstruction that characterized in asthma. In animals, airflow obstruction is usually assessed by measuring airflow resistance during tidal breathing under such invasive technique as tracheostomy and anesthesia. A noninvasive technique for measuring pulmonary function in small animals is needed to evaluate long-term changes in lung function during the course of experimentally produced disease without sacrificing the animal. Purpose: The purpose of this study was to evaluate early bronchoconstrcition after allergen challenge and airway responsiveness (AR) to inhaled methacholine in nonanethetized, unrestrained guinea pigs. Method: Guinea pig model of asthma was sensitized by subcutaneous injection with ovalbumin and challenged by inhalation of aerosolized ovalbumin(1% wt/vol ovlabumin). Airflow obstruction of conscious guinea pig was measured as specific airway resistance (airway resistance $\times$ thoracic gas volume). Airway resistance and thoracic gas volume of conscious guinea pig were assessed by body plethysmography before challenge and at regular intervals for as long as 30 minutes after challenge. AR to aerosolized methacholine of asthma group was compared with that of control group in body plethysmography. Result: Asthma model<> developed in 13 (65%) among 20 guinea pigs, in which early responses occurred in the airways after the exposure to inhalation with ovalbumin. Airway challenge with ovalbumin caused increase in specific airway resistance, which peaked at 6 minutes and amounted to a $231.5{\pm}30.4%$ increase from baseline. AR to aerosolized methacholine of asthma model increased significantly compared with control group. Conclusion: These results have showed a useful animal model to evaluate early bronchoconstrcition after allergen challenge and airway responsiveness in nonanethetized, unrestrained guinea pigs.

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Anti-Immunomodulating Activities in Mycelial Filtrates and Culture Broth of Cordyceps ochraceostromat (동충하초의 균사 및 배양액에 의한 면역 활성 비교)

  • Heo, Jin-Chul;Nam, Sung-Hee;Lee, Kwang-Gil;Yeo, Joo-Hong;Yoon, Chul-Sik;Park, Chul-Hong;Nam, So-Hyun;Son, Min-Sik;Chung, Shin-Kyo;Lee, Sang-Han
    • Food Science and Preservation
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    • v.16 no.2
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    • pp.253-258
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    • 2009
  • This study investigated the effects of mycelium and culture supernatant of Cordyceps ochraceostromat(Co) on air way hyper-responsiveness, pulmonary immune cell infiltration, and Th2 cytokine expression in animal models of atopy and asthma. After ConA(+/-) activation of mouse primary spleen cells, decreased IL-4 and IL-13 cytokine production were seen in the presence of Co mycelium extracts and culture supernatant. The asthma model involved mice sensitized to ovalbumin by i.p. injection treatment; Co mycelium extract was also injected. The atopy model was the dinitrofenylbenzene-treated mouse ear. Ear thicken ing induced by DNFB was decreased by Co mycelium extract, and the extract also inhibited lung cell infiltration in ovalbumin-induced asthmatic mice. The results thus indicated that the Co mycelial extract reduced the undesirable immune responses seen in asthma and atopy.

Anti-hyperglycemic Effect of Bangpungtongseong-san on Type II Diabetes Animal Models (제2형 당뇨 동물모델을 이용한 방풍통성산의 고혈당 개선효과)

  • Ko, Moon Hee;Cho, Hyun Woo;Nho, Jong Hyun
    • Korean Journal of Medicinal Crop Science
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    • v.28 no.4
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    • pp.287-297
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    • 2020
  • Background: Type II diabetes is considered as one of the common diseases. Bangpungtongseongsan (BPS) has been used as a traditional medicine for treating obesity and hypertension in Korea. According to previous reports, it has anti-obesity, anti-chronic asthma, anti-oxidant, and anti-inflammatory properties. However, the effects of BPS on type II diabetes have not yet been elucidated. Thus, in this sutudy, we evaluated the water extracts of BPS using type II diabetes animal models. Methods and Results: Each group was orally administered with BPS (170, 850 and 1,700 mg/kg) for approximately 13 weeks. A mixture of 150 mg/kg metformin and 10 mg/kg sitagliptin (MS) was used as a positive control. The glycated hemoglobin (HbA1c) and glucose levels, and hematological parameters including blood urine nitrogen, creatinine, low density lipoprotein and total cholesterol, were measured using blood samples. Treatment with 170 mg/kg BPS decreased the HbA1c and glucose levels in blood without affecting the weights of the animals. However, threatment with 1,700 mg/kg BPS reduced the weights and fatty liver, and increased the blood glucose level in type II diabetes animal models Conclusions: These results indicate that a low dose of BPS for 13 weeks, which reduces HbA1c and blood glucose levels, could be used for the treatment of type II diabetes. However, further studies are required to elucidate how active ingredients of BPS influence HbA1c and glucose levels in blood.

Immunotherapy of Autoimmune Diseases with Nonantibiotic Properties of Tetracyclines

  • Chan-Su Park;Sang-Hyun Kim;Chong-Kil Lee
    • IMMUNE NETWORK
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    • v.20 no.6
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    • pp.47.1-47.13
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    • 2020
  • Tetracyclines, which have long been used as broad-spectrum antibiotics, also exhibit a variety of nonantibiotic activities including anti-inflammatory and immunomodulatory properties. Tetracyclines bind to the 30S ribosome of the bacteria and inhibit protein synthesis. Unlike antimicrobial activity, the primary molecular target for the nonantibiotic activity of tetracycline remains to be clarified. Nonetheless, the therapeutic efficacies of tetracyclines, particularly minocycline and doxycycline, have been demonstrated in various animal models of autoimmune disorders, such as multiple sclerosis, rheumatoid arthritis, and asthma. In this study, we summarized the anti-inflammatory and immunomodulatory activities of tetracyclines, focusing on the mechanisms underlying these activities. In addition, we highlighted the on-going or completed clinical trials with reported outcomes.