• 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.

• 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.

• Korean Journal of Acupuncture
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• v.22 no.2
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• pp.107-125
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• 2005

Objectives : The aim of this study was to investigate the asthma-suppressive and immuno-regulatory effect of NR-HA(Notopterygii Rhizoma Herbal-acupuncture) at Pyesu(BL13) on OVA(ovalbumin)-induced asthma in mice. Methods : C57BL/6 mice out of all the experimental sloops, except the Normal group and the NR-HA group, were sensitized and challenged with OVA. The mice in the NR-HA group and the OVA-NR-HA group were treated with NR-HA(1%) at Pyesu(BL13). The mice in the OVA-Saline group were injected with saline at Pyesu(BL13). The mice in the OVA-Needle-prick group were treated with a single prick with an injection needle at Pyesu(BL13). NR-HA, saline injection and needle prick were administered for 8 weeks, three times a week Results : in vitro 1. The populations of granulocytes, $CD3e^-/CCR3^+$cells, $CD69^+/CD3e^+$ cells, $CD4^+\;cells\;and\;CD23^+/B220^+$ cells in the OVA-induced asthmatic mouse lungs decreased significantly by NR-HAS(Notopterygii Rhizoma Herbal-acupuncture solution). 2. The lung weight and total cells in lung of the OVA-NR-HA group decreased significantly compared with those of the OVA-Control group. 3. Total leukocytes and eosinophils in BALF of the OVA-NR-HA group decreas ed significantly compared with those of the OVA-Control group. 4. The collagen accumulation in the lung sections of the OVA-NR-HA group decreased significantly compared with that of the OVA-control group. 5. The concentrations of IL-4, IL-5, IL-13, IgE in BALF and serum of the OVA-NR-HA group decreased significantly compared with those of the OVA- Control group. 6. The numbers of $Gr-1^+/CD11b^+,\;CCR3^+,\;CD3e^+, \;CD19^+,\;CD3e^+/CD69^+$ cells in the OVA-NR-HA group decreased significantly compared with those of the OVA-Control group. 7. The mRNA expressions of $TNF-{\alpha}$, IL-5, IL-4 and IL-13 in lung of the OVA-NR-HA group decreased significantly compared with those of the OVA- Control group. 8. The NR-HA group did not show my considerable difference from the Normal group. The OVA-saline group and the OVA-Needle prick group showed suppressive effects on OVA-induced asthma however they were not statistically significant. Conclusion : These results suggest that NR-HA at Pyesu(BL13) is considered to be effective in treating asthma and to be put to practical use in the future asthma clinic.

• 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.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.3
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• pp.581-589
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• 2006

These studies were investigated the effects of Gamicheungpyehwadam-tang (CPHDT) on immune-cell regulation in association with bronchial asthma in OVA-induced mouse model. The administration of 400 mg/kg CPHDT significantly reduced the number of total cells in lung, peripheral lymph node and spleen in OVA-induced bronchial asthma mouse model. The administration of 400 mg/kg CPHDT significantly reduced $CD3^+,{\;}CD19^+$and $CD3^+,{\;}CD69^+$ cell numbers separated from lung, peripheral lymph node and spleen in OVA-induced bronchial asthma mouse model. CPHDT significantly reduced $CD3^+/CCR3^+,{\;}CD4^+,{\;}B220^+/IgE^+$, and $CD3^+/DX5^+$ cell numbers separated from lung, peripheral lymph node and spleen in OVA-induced bronchial asthma mouse model in a dose dependent manner, However, CPHDT significantly reduced $CD8^+$ cell numbers from only lung and spleen. The administration of CPHDT significantly reduced $NK^+$ cell numbers separated from lung of OVA-induced bronchial asthma mouse model in all concentrations, but 200 mg/kg CPHDT reduced $NK^+$ cell numbers separated from peripheral lymph node. These results suggest that CPHDT has anti-asthma and anti-allergy effects. In addition to, CPHDT may be useful treatment of asthma based on the further studies about the individual efficacy search of the components of CPHDT and the adding of variety drugs to CPHDT.

• 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 Korea Journal of Herbology
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• v.26 no.4
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• pp.83-88
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• 2011

Objectives : The aim of this study was to investigate the asthma-suppressive and immuno-regulatory effect of Notopterygii Rhizoma(NR) extract on OVA(ovalbumin)-induced asthma in mice. Methods : C57BL/6 mice out of all the experimental groups, except the Normal group and the NRI group, were sensitized and challenged with OVA. C57BL/6 mice were exposed to OVA three times a week for 12 weeks and analyzed by flow cytometer, ELISA, H&E stain. Results : The concentrations of IL-4, IL-5, IL-13, IgE in serum of the OVA-NRII group decreased significantly compared with those of the OVA-Control group. The number of $Gr-1^+/CD11b^+$, $CCR3^+$, $CD3^+/CD19^+$, $CD3e^+/CD69^+$cells in the OVA-NRI group decreased significantly compared with those of the OVA-Control group. The collagen accumulation in the lung sections of the OVA-NRII group decredased signi- ficantly compared with that of the OVA-Control group. Conclusions : These results suggest that Notopterygii Rhizoma(NR) would be a effective candidate for herbal-originated anti-asthmatic drug. However, this drug should be further studied for characterization of the accurate action and underlying mechanism using variant disease model in the future.

• Biomolecules & Therapeutics
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• v.31 no.2
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• pp.183-192
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• 2023

p38 MAPK has been implicated in the pathogenesis of asthma as well as pro-allergic Th2 cytokines, orosomucoid-like protein isoform 3 (ORMDL3), regulation of sphingolipid biosynthesis, and regulatory T cell-derived IL-35. To elucidate the role of p38 MAPK in the pathogenesis of asthma, we examined the effect of NJK14047, an inhibitor of p38 MAPK, against ovalbumin (OVA)-induced allergic asthma; we administrated NJK14047 before OVA sensitization or challenge in BALB/c mice. As ORMDL3 regulation of sphingolipid biosynthesis has been implicated in childhood asthma, ORMDL3 expression and sphingolipids contents were also analyzed. NJK14047 inhibited antigen-induced degranulation of RBL-2H3 mast cells. NJK14047 administration both before OVA sensitization and challenge strongly inhibited the increase in eosinophil and lymphocyte counts in the bronchoalveolar lavage fluid. In addition, NJK14047 administration inhibited the increase in the levels of Th2 cytokines. Moreover, NJK14047 reduced the inflammatory score and the number of periodic acid-Schiff-stained cells in the lungs. Further, OVA-induced increase in the levels of C16:0 and C24:1 ceramides was not altered by NJK14047. These results suggest that p38 MAPK plays crucial roles in activation of dendritic and mast cells during sensitization and challenge periods, but not in ORMDL3 and sphingolipid biosynthesis.

• 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.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.6
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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.