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The aim of the present study was to establish an integrated network of DNA methylation and RNA expression in an ovalbumin (OVA)‑induced asthma model, and to investigate the epigenetically‑regulated genes involved in asthma development. Genome‑wide CpG‑DNA methylation profiling was conducted through the use of a methylated DNA immunoprecipitation microarray and RNA sequencing was performed using three lung samples from mice with OVA‑induced asthma. A total of 35,401 differentially methylated regions (DMRs) were identified between mice with OVA‑induced asthma and control mice. Of these, 3,060 were located in promoter regions and 370 of the genes containing these DMRs demonstrated an inverse correlation between methylation and gene expression. Kyoto Encyclopedia of Genes and Genomes pathway analysis identified that 368 genes were upregulated or downregulated in OVA‑induced asthma samples, including genes involved in 'chemokine signalling pathway', 'focal adhesion', 'leukocyte transendothelial migration' and 'vascular smooth muscle contraction signaling' pathways. Integrated network analysis identified four hub genes, consisting of three upregulated genes [forkhead box O1 (FOXO1), SP1 transcription factor (SP1) and amyloid β precursor protein (APP)], and one downregulated gene [RUNX family transcription factor 1 (RUNX1)], all of which demonstrated an association between DNA methylation and gene expression. These genes were highly interconnected nodes in the Ingenuity Pathway Analysis module and were functionally significant. A total of four interconnected hub genes, FOXO1, RUNX1, SP1 and APP, were identified from the integrated DNA methylation and gene expression networks involved in asthma development. These results suggested that modulating these four genes could effectively control the development of asthma.

Silica dioxide nanoparticles (SiONPs) are mainly used in the rubber industry; however, they are a major air pollutant in Asia. Thus, extensive research on this issue is required. In this study, we investigated the effects of SiONPs on asthma aggravation and elucidated the underlying mechanism using ovalbumin (OVA)-induced asthmatic mice model and in NCI-H292 cells. Mice exposed to SiONPs showed markedly increased Penh values, inflammatory cell counts, and inflammatory cytokine levels compared to OVA-induced asthmatic mice. Exposure to SiONPs also induced additional airway inflammation and mucus secretion with increases in protein expression levels of thioredoxin-interacting protein (TXNIP), NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome, and interleukin (IL)-1β compared to those in OVA-induced asthmatic mice. Treatment of SiONPs in NCI-H292 cells also significantly increased mRNA expression levels of inflammatory cytokines accompanied with elevation in the levels of TXNIP, NLRP3 inflammasome, and IL-1β proteins in a concentration-dependent manner. Taken together, exposure to SiONPs aggravated asthma development, which is closely related to inflammasome activation. Our results provide useful information about the toxicological effects of SiONPs on asthma exacerbation and suggest the need to avoid SiONP exposure especially in individuals with respiratory diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In this study, we investigated whether 4-hydroxycinnamic acid (HA) has a palliative effect on asthmatic inflammatory responses using a mouse model of ovalbumin (OVA)-induced allergic asthma. The mice were divided into five groups, each consisting of seven females (normal control phosphate-buffered saline); OVA (OVA sensitization/challenge); dexamethasone (DEX, OVA sensitization/challenge + dexamethasone 3 mg/kg); HA-10 and HA-20 OVA sensitization/challenge + HA 10 and 20 mg/kg, respectively). Mice treated with HA showed a reduction in airway hyperresponsiveness and in the number of inflammatory cells in bronchoalveolar lavage fluid (BALF) compared with asthmatic control. HA treatment also reduced the levels of interleukin (IL)-5 and IL-13 in BALF and of OVA-specific immunoglobulin E in the serum compared with asthmatic control. HA treatment relieved airway inflammation and mucus overproduction caused by OVA exposure. Additionally, HA inhibited the increases in levels of nuclear factor kappa B, inducible nitric oxide synthase, and cyclooxygenase-2 that normally occur after OVA exposure. HA treatment also reduced the activity and protein level of matrix metalloproteinase-9. Taken together, HA effectively suppressed asthmatic airway inflammation and mucus production caused by OVA exposure. These findings indicate that HA has the potential to be used as a therapeutic agent for asthma., (© 2019 John Wiley & Sons, Ltd.)

Background: Scrophularia buergeriana Miq. (Scrophulariaceae) (SB) has been used as an oriental medicine for the treatment of inflammatory diseases, such as neuritis and pharyngolaryngitis., Purpose: We explored the therapeutic effects of S. buergeriana ethanol extract (SBE) on airway inflammation in ovalbumin (OVA)-induced asthmatic mice and lipopolysaccharide (LPS)-stimulated RAW264.7 cells., Methods: Mice were intraperitoneally injected with OVA on days 0 and 14 to elevate the immune response. On days 21 to 23, the mice were challenged with OVA solution and SBE (20 and 40 mg/kg) was administered daily by oral gavage from days 18 to 23. RAW264.7 cells were pretreated with SBE 1 h before LPS stimulation., Results: SBE administration effectively suppressed inflammatory cell infiltration, the expression of interleukin (IL)-5, IL-13, and IL-17, immunoglobulin E, and airway hyperresponsiveness in an OVA-induced allergic asthma model. A reduction in histological alterations, including airway inflammation and mucus hypersecretion, was observed. These effects of SBE were accompanied by a decrease in matrix metalloproteinase-9 (MMP-9) expression and nuclear factor kappa B (NF-κB) phosphorylation. These responses were observed in LPS-stimulated RAW264.7 cells. SBE treatment reduced the mRNA expression of tumor necrosis factor (TNF)-α, IL-6, and MMP-9, and NF-κB phosphorylation, in LPS-stimulated RAW264.7 cells., Conclusion: Our results indicated that SBE effectively attenuated airway inflammation in an OVA-induced allergic asthma model. These properties of SBE were thought to be involved in the suppression of NF-κB phosphorylation, suggesting that the material has the potential to regulate the development of allergic asthma., Competing Interests: Conflict of interest No competing financial interests exist., (Copyright © 2019 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Dipsacus asperoides C. Y. Cheng et T. M. Ai (DA) has been used in China as a traditional medicine to treat lumbar and knee pain, liver dysfunction, and fractures. We explored the suppressive effect of DA on allergic asthma using an ovalbumin (OVA)-induced asthma model. In the asthma model, female Balb/c mice were sensitized to OVA on day 0 and 14 to boost immune responses and then exposed to OVA solution by using an ultrasonic nebulizer on days 21 to 23. DA (20 and 40 mg/kg) was administered to mice by oral gavage on days 18 to 23. Methacholine responsiveness was determined on day 24 using a plethysmography. On day 25, we collected bronchoalveolar lavage fluid, serum, and lung tissue from animals under anesthesia. DA treatment effectively inhibited methacholine responsiveness, inflammatory cell infiltration, proinflammatory cytokines such as interleukin (IL)-5 and IL-13, and immunoglobulin (Ig) E in OVA-induced asthma model. Reductions in airway inflammation and mucus hypersecretion, accompanied by decreases in the expression of inducible nitric oxide synthase (iNOS) and the phosphorylation of nuclear factor kappa B (NF-κB), were also observed. Our results indicated that DA attenuated the asthmatic response, and that this attenuation was closely linked to NF-κB suppression. Thus, this study suggests that DA is a potential therapeutic for allergic asthma.

S-Allyl cysteine (SAC) is an active component in garlic and has various pharmacological effects, such as anti-inflammatory, anti-oxidant, and anti-cancer activities. In this study, we explored the suppressive effects of SAC on allergic airway inflammation induced in an ovalbumin (OVA)-induced asthma mouse model. To induce asthma, BALB/c mice were sensitized to OVA on days 0 and 14 by intraperitoneal injection and exposed to OVA from days 21 to 23 using a nebulizer. SAC was administered to mice by oral gavage at a dose of 10 or 20 mg/kg from days 18 to 23. SAC significantly reduced airway hyperresponsiveness, inflammatory cell counts, and Th2 type cytokines in bronchoalveolar lavage fluid induced by OVA exposure, which was accompanied by reduced serum OVA-specific immunoglobulin E. In histological analysis of the lung tissue, administration of SAC reduced inflammatory cell accumulation into lung tissue and mucus production in airway goblet cells induced by OVA exposure. Additionally, SAC significantly decreased MUC5AC expression and nuclear factor-κB phosphorylation induced by OVA exposure. In summary, SAC effectively suppressed allergic airway inflammation and mucus production in OVA-challenged asthmatic mice. Therefore, SAC shows potential for use in treating allergic asthma., (Copyright © 2019. Published by Elsevier B.V.)

Genipin is a natural compound isolated from the fruit of Gardenia jasminoides with various pharmacological effects. In this study, we investigated whether genipin effectively alleviates allergic responses in a murine model of ovalbumin (OVA)-induced asthma. The mice were administered an intraperitoneal injection of OVA on day 0 and 14 to boost the immune response; genipin was then administered from day 18 to 23 by oral gavage. On days 21 to 23, mice were OVA-challenged using am ultrasonic nebulizer, and airway hyperresponsiveness (AHR) was determined on day 24 by plethysmography. Genipin significantly reduced the inflammatory cell count in bronchoalveolar lavage fluids (BALF) and AHR, which were accompanied by lower interleukin-5 (IL-5), IL-13 and OVA-specific immunoglobulin (Ig) E levels in the BALF or serum from OVA-induced asthmatic mice. In histology, genipin significantly decreased airway inflammation and mucus hypersecretion in OVA-induced asthmatic mice. Additionally, genipin inhibited OVA-induced increases in the expression of inducible nitric oxide synthase and cyclooxygenase-2 proteins. Further, genipin reduced the activity and protein levels of matrix metalloproteinase-9 in lung tissue from OVA induced asthmatic mice. Overall, genipin effectively alleviated the asthmatic inflammatory response in an OVA-induced asthmatic model. Therefore, our results suggest that genipin has therapeutic potential for treating asthma., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Artemisia argyi is a traditional herbal medicine in Korea and commonly called as mugwort. It is traditionally used as food source and tea to control abdominal pain, dysmenorrhea, uterine hemorrhage, and inflammation., Aim of the Study: We investigated the effects of A. argyi (TOTAL) and dehydromatricarin A (DA), its active component on ovalbumin (OVA)-induced allergic asthma., Materials and Methods: The animals were sensitized on day 0 and 14 by intraperitoneal injection of OVA with aluminum hydroxide. On day 21, 22 and 23 after the initial sensitization, the animals received an airway challenge with OVA for 1h using an ultrasonic nebulizer. TOTAL (50 and 100mg/kg) or DA (10 and 20mg/kg) were administered to mice by oral gavage once daily from day 18-23. Airway hyperresponsiveness (AHR) was measured 24h after final OVA challenge., Result: TOTAL and DA treated animals reduced inflammatory cell counts, cytokines and AHR in asthmatic animals, which was accompanied with inflammatory cell accumulation and mucus hypersecretion. Furthermore, TOTAL and DA significantly declined Erk phosphorylation and the expression of MMP-9 in asthmatic animals., Conclusion: In conclusion, we indicate that Total and DA suppress allergic inflammatory responses caused by OVA challenge. It was considered that A. argyi has a potential for treating allergic asthma., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Copper oxide nanoparticles (CuONPs), metal oxide nanoparticles were used in multiple applications including wood preservation, antimicrobial textiles, catalysts for carbon monoxide oxidation and heat transfer fluid in machines. We investigated the effects of CuONPs on the respiratory system in Balb/c mice. In addition, to investigate the effects of CuONPs on asthma development, we used a murine model of ovalbumin (OVA)-induced asthma. CuONPs markedly increased airway hyper-responsiveness (AHR), inflammatory cell counts, proinflammatory cytokines and reactive oxygen species (ROS). CuONPs induced airway inflammation and mucus secretion with increases in phosphorylation of the MAPKs (Erk, JNK and p38). In the OVA-induced asthma model, CuONPs aggravated the increased AHR, inflammatory cell count, proinflammatory cytokines, ROS and immunoglobulin E induced by OVA exposure. In addition, CuONPs markedly increased inflammatory cell infiltration into the lung and mucus secretions, and MAPK phosphorylation was elevated compared to OVA-induced asthmatic mice. Taken together, CuONPs exhibited toxicity on the respiratory system, which was associated with the MAPK phosphorylation. In addition, CuONPs exposure aggravated the development of asthma. We conclude that CuONPs exposure has a potential toxicity in humans with respiratory disease.

Zingiber mioga (Thunb.) Roscoe (ZM) is a traditional medicine, used to treat inflammatory diseases. The present study aimed to evaluate the inhibitory effects of ZM on the inflammatory response in lipopolysaccharide (LPS)‑stimulated RAW264.7 murine macrophage cells and in a mouse model of ovalbumin (OVA)‑induced allergic asthma. Mice received OVA sensitization on day 0 and 14, and were challenged with OVA between days 21 and 23. ZM was administered to the mice at a dose of 30 mg/kg, 1 h prior to OVA challenge. In LPS‑stimulated RAW264.7 cells, ZM significantly decreased nitric oxide (NO) and tumor necrosis factor (TNF)‑α production in a concentration‑dependent manner, and mRNA expression of inducible NO synthase (iNOS), TNF‑α and matrix metalloproteinase (MMP)‑9 was reduced. In addition, treatment with ZM decreased the inflammatory cell count in bronchoalveolar lavage fluid from the mice, and reduced the expression of interleukin (IL)‑4, IL‑5, IL‑13, eotaxin and immunoglobulin E. ZM also reduced airway hyperresponsiveness in OVA‑challenged mice, and attenuated the infiltration of inflammatory cells and mucus production in the airways, with a decrease in the expression of iNOS and MMP‑9 in lung tissue. In conclusion, the results of the present study indicate that ZM effectively inhibits inflammatory responses. Therefore, it may be that ZM has potential as a therapeutic agent for use in inflammatory diseases.

Thuja orientalis (TO) may be used as a herbal remedy for the treatment of numerous inflammatory diseases. In the present study, the effects of TO were evaluated on airway inflammation in ovalbumin (OVA)‑induced allergic asthma and RAW264.7 murine macrophage cells. The effects of TO on the production of proinflammatory mediators, were determined in RAW264.7 cells that had been stimulated with lipopolysaccharide (LPS). Furthermore, an in vivo experiment was performed on mice that were sensitized to OVA and then received an OVA airway challenge. TO was administered by daily oral gavage at a dose of 30 mg/kg, 21‑23 days after the initial OVA sensitization. TO was shown to reduce nitric oxide production and reduce the relative mRNA expression levels of inducible nitric oxide synthase (iNOS), interleukin (IL)‑6, cyclooxygenase‑2, matrix metalloproteinase (MMP)‑9, and tumor necrosis factor‑α in RAW264.7 cells stimulated with LPS. In addition, TO markedly decreased the inflammatory cell counts in bronchial alveolar lavage fluid, reduced the levels of IL‑4, IL‑5, IL‑13, eotaxin and immunoglobulin E, and reduced airway hyperresponsivenes, in the OVA sensitized mice. Furthermore, TO attenuated airway inflammation and mucus hypersecretion, induced by the OVA challenge of the lung tissue. TO also reduced the expression of iNOS and MMP‑9 in lung tissue. In conclusion, TO exerted anti‑inflammatory effects in an OVA‑induced allergic asthma model, and in LPS‑stimulated RAW264.7 cells. These results suggest that TO may be a useful therapeutic agent for the treatment of inflammatory diseases, including allergic asthma.

Asthma is a common chronic inflammatory airway disease that is recognized as a major public health problem. In this study, we evaluated the effects of melatonin on allergic asthma using a murine model of ovalbumin (OVA)-induced allergic asthma and BEAS-2B cells. To induce allergic asthma, the mice were sensitized and airway-challenged with OVA. Melatonin was administered by intraperitoneal injection once per day at doses of 10 and 15 mg/kg from days 21 to 23 after the initial OVA sensitization. We investigated the effects of melatonin on proinflammatory cytokines and matrix metalloproteinase-9 (MMP-9) activity and expression in tumor necrosis factor (TNF)-α-stimulated BEAS-2B cells. The administration of melatonin significantly decreased the number of inflammatory cells, airway hyperresponsiveness, and immunoglobulin (Ig) E with reductions in interleukin (IL)-4, IL-5, and IL-13. Melatonin attenuated the airway inflammation and the mucus production in lung tissue and significantly suppressed elevated MMP-9 expression and activity induced by an OVA challenge. In TNF-α-stimulated BEAS-2B cells, treatment with melatonin significantly reduced the levels of proinflammatory cytokines and lowered the expression and activity of MMP-9. These results indicate that melatonin effectively suppressed allergic asthma induced by an OVA challenge. The results suggest a potential role for melatonin in treating asthma., (Copyright © 2014. Published by Elsevier GmbH.)

Siegesbeckia glabrescens (SG) is a plant growing in Korea that is used as a traditional medicine for various inflammatory diseases. In this study, we investigated the protective effects of SG extract on allergic asthma in an ovalbumin (OVA)-induced asthma murine model and lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Female BALB/c mice were sensitized by intraperitoneal injection of OVA on days 0 and 14 and then challenged with OVA from days 21 to 23. SG (30mg/kg) was administered by oral gavage 1h before the OVA challenge. LPS-stimulated RAW264.7 cells were evaluated to determine their levels of nitric oxide (NO). The SG significantly reduced the number of inflammatory cells in bronchoalveolar lavage (BAL) fluid and also reduced IL-4, IL-5, IL-13, eotaxin and immunoglobulin E in OVA-sensitized/challenged mice. SG also effectively reduced airway inflammation and mucus overproduction in lung tissue in addition to decreasing the expression of iNOS and COX-2. In LPS-stimulated RAW264.7 cells, SG treatment significantly reduced the levels of NO. These findings indicate that SG effectively suppressed inflammatory responses, and its effects appear to be related to reduction in iNOS and COX-2 expression. Therefore, we suggest that SG may have potential use as a therapeutic agent for inflammatory diseases such as allergic asthma., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Picrasma quassioides (D.Don) Benn. (PQ) is used in traditional medicine for the treatment of inflammatory conditions, including gastritis. This study aimed to evaluate the inhibitory effects of PQ on the inflammatory responses in mice with allergic asthma induced by ovalbumin (OVA) and in lipopolysaccharide (LPS)‑stimulated RAW264.7 cells. To induce allergic asthma, the mice underwent OVA sensitization on days 0 and 14 and then were challenged with OVA from days 21‑23. The mice were administered 15 and 30 mg/kg doses of PQ 1 h prior to the OVA challenge. The PQ treatment decreased the inflammatory cell count in the bronchoalveolar lavage fluid of the mice and reduced the levels of interleukin (IL)‑4, IL‑5, IL‑13 and immunoglobulin (Ig)E when compared with those in the OVA group. The PQ treatment also reduced the airway hyperresponsiveness induced by the OVA challenge, attenuated the recruitment of inflammatory cells and the mucus production in the airways of the mice. In the LPS‑stimulated RAW264.7 cells, the PQ treatment reduced the overexpression of inducible nitric oxide synthase (iNOS). The results indicated that PQ inhibits inflammatory responses in mice with OVA‑sensitized/challenged allergic asthma and in LPS‑stimulated RAW264.7 cells. These effects were considered to be associated with the suppression of iNOS expression. Therefore, PQ may have the potential to treat airway inflammatory diseases, including allergic asthma.

EC-18 is a synthetic monoacetyldiaglyceride that is a major constituent in antlers of Sika deer (Cervus nippon Temmenick). In this study, we evaluated the protective effects of EC-18 on Th2-type cytokines, eosinophil infiltration, and other factors in an aluminum hydroxide/ovalbumin (OVA)-induced murine asthma model. Mice were sensitized on days 0 and 14 by intraperitoneal injection of OVA with aluminum hydroxide. On days 21, 22 and 23 after the initial sensitization, the mice received an airway challenge with OVA for 1h using an ultrasonic nebulizer. EC-18 was administered to mice by oral gavage at doses of 30mg/kg and 60mg/kg once daily from day 18 to 23. Methacholine responsiveness was measured 24h after the final OVA challenge, and the bronchoalveolar lavage fluid (BALF) was collected 48h after the final OVA challenge. EC-18 significantly reduced methacholine responsiveness, T helper type 2 (Th2) cytokines, eotaxin-1, immunoglobulin (Ig) E, IgG, and the number of inflammatory cells. In addition, EC-18-treated mice exhibited the reduction in the expression of inducible nitric oxide synthase (iNOS) in lung tissue. In the histological analysis using hematoxylin-eosin stain and periodic acid-Schiff stain, EC-18 attenuated the infiltration of inflammatory cells into the airway and reduced the level of mucus production. Our results showed that EC-18 effectively suppressed the asthmatic response induced by OVA challenge. These effects were considered to be associated with iNOS suppression. In conclusion, this study suggests that EC-18 may be a therapeutic agent for allergic asthma., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Homoegonol is a lignan derived from styraxlignolide A, which was isolated from Styrax japonica, a medicinal plant widely used for treatment of inflammatory diseases in Korea. We investigated the efficacy of homoegonol for the treatment of allergic asthma using an ovalbumin (OVA)-induced murine asthma model. The mice were sensitized through intraperitoneal injections of OVA on days 0 and 14. On days 21, 22 and 23 after the initial OVA sensitization, the mice were received OVA airway challenge. Homoegonol was administered by oral gavage at a dose of 30 mg/kg 1 h prior to the OVA challenge. The homoegonol-treated mice exhibited reduced inflammatory cell counts and Th2 cytokines in BALF, AHR, and IgE in the serum compared with the OVA-sensitized/challenged mice. The histological analysis of the lung tissue revealed that the administration of homoegonol attenuated the airway inflammation and the mucus overproduction in airway epithelial lesions induced by OVA through a reduction in expression of inducible nitric oxide synthase and matrix metalloproteinase-9. These findings indicate that homoegonol effectively suppresses the asthmatic responses induced by OVA challenge and suggests that homoegonol exhibits potential as therapeutic drug for allergic asthma.

Pycnogenol® (PYC) is a standardized extracts from the bark of the French maritime pine (Pinus maritime) and used as a herbal remedy for various diseases. In this study, we evaluated the effects of PYC on airway inflammation using a model of ovalbumin (OVA)-induced allergic asthma and RAW264.7 cells. PYC decreased nitric oxide production and reduced the interleukine (IL)-1β and IL-6 levels in LPS-stimulated RAW264.7 cells. PYC also reduced the expression of inducible nitric oxide synthase (iNOS) and matrix metalloproteinase (MMP)-9 and enhanced the expression of hemeoxygenase (HO)-1. In the in vivo experiment, PYC decreased the inflammatory cell count and the levels of IL-4, IL-5, IL-13, and immunoglobulin (Ig) E in BALF or serum. These results are consistent with the histological analysis findings, which showed that PYC attenuated the airway inflammation and mucus hypersecretion induced by OVA challenge. In addition, PYC enhanced the expression of HO-1. In contrast, PYC inhibited the elevated expression of iNOS and MMP-9 proteins induced by OVA challenge. In conclusion, PYC exhibits protective effects against OVA-induced asthma and LPS-stimulated RAW264.7 cells. These results suggest that PYC has potential as a therapeutic agent for the treatment of allergic asthma., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Diallyl disulfide (DADS) is a major organosulfur compound found in garlic oil that is widely used as a flavoring agent. In this study, we evaluated the effects of DADS on airway inflammation using an ovalbumin-induced model of allergic asthma and RAW264.7 cells. DADS decreased nitric oxide production with a reduction in the levels of interleukins (IL)-1β and IL-6 in RAW264.7 cells stimulated with LPS. DADS also reduced the expression of proinflammatory proteins including inducible nitric oxide synthase (iNOS), nuclear factor (NF)-κB, and matrix metalloproteinase (MMP)-9, and it enhanced the expression of antioxidant proteins including Nrf-2 and hemeoxygenase (HO)-1. In in vivo experiments, DADS decreased the inflammatory cell count in the bronchoalveolar lavage fluid (BALF) with IL-4, IL-5, IL-13, and immunoglobulin (Ig) E. These results were consistent with the histological analysis. DADS attenuated the airway inflammation and mucus hypersecretion induced by OVA challenge. In addition, DADS induced the activation of Nrf-2 and the expression of HO-1. In contrast, DADS reduced the activation of NF-κB, iNOS and MMP-9. In conclusion, DADS reduced the airway inflammation via regulation of Nrf-2/HO-1 and NF-κB. These results suggest that DADS might represent a useful new oral therapy to treat allergic asthma., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

EBM84 is a traditional herbal medicine and a combination of extracts obtained from Pinellia ternata and Zingiber officinale. It is traditionally used to treat vomiting, nausea, sputum and gastrointestinal disorders, and functions is an effective expectorant. In this study, we evaluated the protective effects of EBM84 on asthmatic responses, particularly mucus hypersecretion in an ovalbumin (OVA)-induced murine model of asthma. We also analyzed EBM84 composition using high performance liquid chromatography. Animals were sensitized on days 0 and 14 via intraperitoneal injection using 20 µg OVA. On days 21, 22 and 23 after initial sensitization, the mice received an airway challenge with OVA (1% w/v in PBS) for 1 h using an ultrasonic nebulizer (NE-U12). EBM84 was administered by gavage to the mice at doses of 16.9, 33.8 and 67.5 mg/kg once daily from days 18 to 23. EBM84 administration significantly lowered elevated levels of interleukin (IL)-4, IL-13, eotaxin and immunoglobulin (Ig)E in the bronchoalveolar lavage fluid or plasma. Airway inflammation and mucus hypersecretion were attenuated following EBM84 administration. EBM84 also inhibited the overexpression of mucin 5AC (MUC5AC) induced by OVA challenge in lung tissue. This result was consistent with the immunohistochemistry results. Our results indicate that EBM84 effectively inhibited airway inflammation and mucus hypersecretion via the downregulation of T helper 2 (Th2) cytokines, which reduced MUC5AC expression. Therefore, EBM84 has potential as a useful medicine for the treatment of allergic asthma.