Ovalbumin-induced Allergic Asthma Research Articles

Protective effect of miR-138-5p inhibition modified human mesenchymal stem cell on ovalbumin-induced allergic rhinitis and asthma syndrome.

The objective of the study is to evaluate the protective effects of human mesenchymal stem cells (hMSCs) modified with miR‐138‐5p inhibitor against the allergic rhinitis and asthma syndrome (ARAS). MiR‐138‐5p or negative control was transfected into hMSCs, and fluorescence‐activated cell sorting was used to evaluate hMSC surface markers. Quantitative real‐time PCR (qRT‐PCR) was used to evaluate miR‐138‐5p, SIRT1, caspase‐3, IL‐6, IL‐1β and TNF‐α levels after TNF‐α and IL‐6 stimulations. hMSCs with or without miR‐138‐5p inhibition was intranasally administered into ARAS mice (n = 10 each group), followed by monitoring sneezing and nasal rubbing events to evaluate the allergic symptoms. Histamine, ovalbumin‐specific IgE, IgG2a, IgG1 and LTC4 release were monitored in the serum and nasal lavage fluid using enzyme‐linked immunosorbent assay. Expression of SIRT1 and HMGB1/TLR4 pathway in nasal mucosa was assessed. After miR‐138‐5p inhibitor transfection, the hMSC lineage was preserved. Binding between SIRT1 and miR‐138‐4p was observed, and miR‐138‐5p inhibition led to upregulation of SIRT1. Inhibition of miR‐138‐5p led to attenuated inflammatory responses of hMSCs upon TNF‐α and IL‐6 stimulation, and allergic symptoms in mice, as well as histamine and ovalbumin‐specific IgG release. hMSCs with miR‐138‐5p inhibition showed characteristics of activated SIRT1 and inhibited HMGB1/TLR4 pathway. Inhibition of miR‐138‐5p in hMSCs enhanced its effects in attenuating inflammatory responses and allergic reaction in the ARAS model, which is presumably regulated by SIRT1 and the HMGB1/TLR4 pathway.

4-CMTB Ameliorates Ovalbumin-Induced Allergic Asthma through FFA2 Activation in Mice.

Free fatty acid receptor 2 (FFA2, also known as GPR43), a G-protein-coupled receptor, has been known to recognize short-chain fatty acids and regulate inflammatory responses. FFA2 gene deficiency exacerbated disease states in several models of inflammatory conditions including asthma. However, in vivo efficacy of FFA2 agonists has not been tested in allergic asthma. Thus, we investigated effect of 4-chloro-α-(1-methylethyl)-N-2-thiazoylylbenzeneacetanilide (4-CMTB), a FFA2 agonist, on antigen-induced degranulation in RBL-2H3 cells and ovalbumin-induced allergic asthma in BALB/c mice. Treatment of 4-CMTB inhibited the antigen-induced degranulation concentration-dependently. Administration of 4-CMTB decreased the immune cell numbers in the bronchoalveolar lavage fluid and suppressed the expression of inflammatory Th2 cytokines (IL-4, IL-5, and IL-13) in the lung tissues. Histological studies revealed that 4-CMTB suppressed mucin production and inflammation in the lungs. Thus, results proved that FFA2 functions to suppress allergic asthma, suggesting 4-CMTB activation of FFA2 as a therapeutic tool for allergic asthma.

Deficiency of voltage-gated proton channel Hv1 aggravates ovalbumin-induced allergic lung asthma in mice

Asthma is a chronic airway inflammation that caused by many factors. The voltage-gated proton channel Hv1 has been proposed to extrude excessive protons produced by NADPH oxidase (NOX) from cytosol to maintain its activity during respiratory bursts. Here, we showed that loss of Hv1 aggravates ovalbumin (OVA)-induced allergic lung asthma in mice. The numbers of total cells, eosinophils and neutrophils in bronchoalveolar lavage fluid (BALF) of Hv1-deficiency (KO) mice are obviously increased after OVA challenge compared with that of wild-type (WT) mice. Histopathological staining reveals that Hv1-deficiency aggravates OVA-induced inflammatory cell infiltration and goblet cell hyperplasia in lung tissues. The expression of IL-4, IL-5 and IL-13 are markedly increased in lung tissues of OVA-challenged KO mice compared with that of WT mice. Furthermore, the expression levels of NOX2, NOX4 and DUOX1 are dramatically increased, while the expression levels of SOD2 and catalase are significantly reduced in lung tissues of OVA-challenged KO mice compared with that of WT mice. The production of ROS in lung tissues of KO mice is significantly higher than that of WT mice after OVA challenge. Our data suggest that Hv1-deficiency might aggravate the development of allergic asthma through increasing ROS production.

Suppressive Effect of CYM50358 S1P4 Antagonist on Mast Cell Degranulation and Allergic Asthma in Mice.

Levels of sphingosine 1-phosphate (S1P), an intercellular signaling molecule, reportedly increase in the bronchoalveolar lavage fluids of patients with asthma. Although the type 4 S1P receptor, S1P4 has been detected in mast cells, its functions have been poorly investigated in an allergic asthma model in vivo. S1P4 functions were evaluated following treatment of CYM50358, a selective antagonist of S1P4, in an ovalbumin-induced allergic asthma model, and antigen-induced degranulation of mast cells. CYM50358 inhibited antigen-induced degranulation in RBL-2H3 mast cells. Eosinophil accumulation and an increase of Th2 cytokine levels were measured in the bronchoalveolar lavage fluid and via the inflammation of the lungs in ovalbumin-induced allergic asthma mice. CYM50358 administration before ovalbumin sensitization and before the antigen challenge strongly inhibited the increase of eosinophils and lymphocytes in the bronchoalveolar lavage fluid. CYM50358 administration inhibited the increase of IL-4 cytokines and serum IgE levels. Histological studies revealed that CYM50358 reduced inflammatory scores and PAS (periodic acid–Schiff)-stained cells in the lungs. The pro-allergic functions of S1P4 were elucidated using in vitro mast cells and in vivo ovalbumin-induced allergic asthma model experiments. These results suggest that S1P4 antagonist CYM50358 may have therapeutic potential in the treatment of allergic asthma.

Human amniotic membrane mesenchymal stem cell-conditioned medium reduces inflammatory factors and fibrosis in ovalbumin-induced asthma in mice.

What is the central question of this study? Is mesenchymal stem cell-conditioned medium capable of improving the pathological alterations of ovalbumin-induced asthma in mice? What is the main finding and its importance? Our study indicated that human amniotic membrane mesenchymal stem cell-conditioned medium is capable of modulating inflammation, fibrosis, oxidative stress and the pathological consequences of ovalbumin-induced allergic asthma in mice. Paracrine factors secreted by mesenchymal stem cells (MSCs) have immunomodulatory, anti-inflammatory and antifibrotic properties, and the conditioned medium (CM) of these cells might have functional capabilities. We examined the effects of human amniotic membrane MSC-CM (hAM-MSC-CM) on ovalbumin (OVA)-induced asthma. Forty male Balb/c mice were randomly divided into the following four groups: control; OVA (sensitized and challenged with OVA); OVA+CM (sensitized and challenged with OVA and treated with hAM-MSC-CM); and OVA+Placebo (sensitized and challenged with OVA and treated with placebo). Forty-eight hours after the last challenge, serum and bronchoalveolar lavage fluid samples were collected and used for evaluation of inflammatory factors and cells, respectively. Lung tissue sections were stained with Haematoxylin and Eosin or Masson's Trichrome to evaluate pathological changes, and oxidative stress was assessed in fresh lung tissues. Treatment with hAM-MSC-CM significantly hindered histopathological changes and fibrosis and reduced the total cell count and the percentage of eosinophils and neutrophils in bronchoalveolar lavage fluid. Furthermore, it reduced serum levels of immunoglobulinE, interleukin-4, transforming growth factor-β and lung malondialdehyde. It also increased serum levels of interferon-γ and interleukin-10, in addition to the enzymatic activity of glutathione peroxidase, catalase and superoxide dismutase in lung tissue in comparison to the OVA and OVA+Placebo groups. This study showed that administration of hAM-MSC-CM can improve pathological conditions, such as inflammation, fibrosis and oxidative stress, in OVA-induced allergic asthma.

Betalain Alleviates Airway Inflammation in an Ovalbumin-Induced-Asthma Mouse Model via the TGF-β1/Smad Signaling Pathway.

Global industrialization not only improved the quality life of millions but also paved the way to solving many health problems. One among them is allergic asthma, which affects approximately 20% of the global population. Poor air quality is the major culprit in allergic asthma, which not only affects the individual's health, but also impairs his or her life quality and that of family members. Asthma is a chronic pulmonary inflammatory disease characterized by excess mucus production, airway hyperresponsiveness, and bronchoconstriction. Inhalation of corticosteroids, leukotriene modifiers, and β-adrenergic agonists is one treatment prescribed to control the symptoms of asthma, but there is still no effective cure. Phytochemicals such as carotenoids, phenolics, alkaloids, and nitrogen and organosulfur compounds are proven to possess immense pharmacological properties. Betalain is one such phytochemical present in plants of the order Caryophyllales. It is a water-soluble nitrogen-based pigment proven to possess antimicrobial, antioxidant, anti-inflammatory, hepatoprotective, antilipidemic, antidiabetic, and anticancer properties. We examined the curative potential of betalain against allergic asthma in a mouse model. Betalain treatment effectively decreased lung weight and infiltration of inflammatory cells in BAL fluid, and lowered IgE, eotaxin, and cytokine levels in asthma-induced mice. It also improved pulmonary mechanics and decreased oxidative stress and nitric oxide levels. Betalain significantly decreased gene expression of TGF-β and its downstream signaling Smad proteins. Lung histology confirmed that betalain protected the lung tissue of mice from ovalbumin-induced allergic asthma. Overall, our results show that betalain is a potent antiallergic drug that effectively protects mice from ovalbumin-induced allergic asthma. With further research, it can be prescribed as a treatment for asthma in humans.

Anti-Inflammatory Activity of Extract Mixture of Annona senegalensis Pers. and Piliostigma thonningii (Schum.)

Introduction: Annona senegalensis Pers (Annonaceae) and Piliostigma thonningii (Schum.) (Leguminoseae) are two medicinal plants used, often in combination, in traditional Togolese medicine for the treatment of diseases with an inflammatory component.
 Objective: The aim of this study is to evaluate the anti-inflammatory effect of the hydro-ethanolic extract (EHEM) of the combination of A. senegalensis and P. thonningii (1: 1, m: m).
 Methods: The ovalbumin-induced allergic airway asthma model was used. Animals made asthmatic were treated with EHEM at doses of 250 and 500 mg / kg. Inflammation markers including histamine, nitric oxide (NO), vascular leakage, leukocyte infiltration in the airways, and malondialdehyde (MDA), were measured.
 Results: Compared to the SNT group, EHEM inhibits the infiltration of the airways by leukocytes (850,00 × 103 ± 50 cells / mL vs 1830 × 103 ± 53,85 cells / mL for ST500 mg / kg, P <0,05). It inhibited vascular permeability to Evans Blue (10,40 ± 0,270 μg / mL vs ST500, p<0,05). It inhibited histamine release (13,95 ± 0,937 μg / mL vs 32,78 ± 1,044 μg / mL, p<0,05) and NO production (0,211 ± 0,008 Μm vs 0,315 ± 0,022 μM, p<0,05). It finally inhibited MDA production (14,66 ± 0,533 nM / mL vs 9,014 ± 0,366 nM / mL and 7,149 ± 0,300 nM / mL, p<0,05) in lung tissue.
 Conclusion: Our results suggest that EHEM inhibits OVA-induced inflammation. These results justify the use of this combination of plants in traditional Togolese medicine.
 Keywords: Inflammation, malondialdehyde, Annona senegalensis, Piliostigma thonningii.

Augmented angiogenic transcription factor, SOX18, is associated with asthma exacerbation

Background Asthma characterized by airway hyperresponsiveness, inflammation, fibrosis, and angiogenesis. SRY-related HMG-box 18 (SOX18) is an important transcription factor involved in angiogenesis, tissue injury, wound-healing, and in embryonic cardiovascular and lymphatic vessels development. The role of angiogenic transcription factors, SOX18 and the related, prospero homeobox 1 (PROX1) and chicken ovalbumin upstream promoter transcription factor II (COUP-TFII), in asthma has had limited study. Objective In this study, we aimed to elucidate the role of SOX18 in the pathogenesis of bronchial asthma. Methods Plasma SOX18 protein was measured in control subjects, and subject with stable or exacerbated asthma. SOX18, PROX1, and COUP-TFII protein was measured by western blot, and immunohistochemistry in a murine model of ovalbumin-induced allergic asthma (OVA). SOX18, PROX1, and COUP-TFII protein was measured in lung human microvascular endothelial cells (HMVEC-L) and normal human bronchial epithelial (NHBE) cells treated with house dust mite (Der p1). Results Plasma SOX18 tended to be higher in subject with asthma compared to control subjects and increased more during exacerbation as compared to stable disease. In mice, OVA challenge lead to increased lung SOX18, PROX1, COUP-TFII, mucous gland hyperplasia and submucosal collagen. In NHBE cells, SOX18, PROX1 and COUP-TFII increased following Der p1 treatment. SOX18 protein increased in HMVEC-L following Der p1 treatment. Conclusion These results suggest that SOX18 may be involved in asthma pathogenesis and be associated with asthma exacerbation.

Mechanistic investigation of PPARγ-facilitated anti-asthmatic effects of Galangin (Norizalpinin): Insights from in silico and in vivo analyses

Peroxisome proliferator-activated receptor gamma (PPARγ) is a multifaceted ligand-activated transcription factor that regulates inflammatory responses in asthma pathophysiology. The present study corroborates PPARγ-mediated anti-asthmatic action of the flavonoid, galangin (norizalpinin). In silico molecular interactions reveal that galangin formed three H-bonds (Glu291, Leu340 and Ser342) and a π-sigma bond (Arg288) with PPARγ, contributing to the binding affinity and stability of the complex. In vivo studies explore the role of galangin as a propitious PPARγ agonist in mitigating airway inflammation, thereby excluding ligand-independent action of PPARγ. Accordingly, oral administration of galangin significantly ameliorated airway hyperresponsiveness, inflammation and goblet cell hyperplasia by the suppression of IL-4, 5, 13, 17, TNF-α, NO, ROS, EPO, IgE and increase of IFN-γ in ovalbumin-induced allergic asthma model. PPARγ expression (mRNA and protein) studies were performed to elucidate a possible mechanism by which galangin modulates. Furthermore, to eliminate PPARγ-independent effects of galangin, a specific PPARγ antagonist (GW9662) was administered, which dramatically reversed the effects of galangin on PPARγ up-regulation, confirming the pleiotropic role of galangin as a PPARγ agonist in asthma therapeutics. Taken together, our findings communicate that PPARγ plays as a master regulator in the anti-asthmatic action of galangin.

Rubusoside alleviates the ovalbumin-induced mice allergic asthma by modulating the NF-κB activation.

The anti-inflammatory and anti-asthmatic effects of rubusoside (Rbs) were investigated in the ovalbumin (OVA)-induced asthmatic mice, followed by effective attenuation of Rbs treatment on the airway hyperresponsiveness and reduction of inflammatory cells inside the bronchoalveolar lavage fluid (BALF). The mitigation of inflammatory infiltration as a result of Rbs treatment was histologically observed in these mice lungs. Rbs contributed to the decrease of inflammatory cytokines (TNF-α, IL-13, IL-6, IL-5, and IL-4) inside the BALF of mice with asthma. A decline of OVA-dependent IgE and IgG1 inside the serum was also noticed in these mice. Rbs was proved to enhance the mRNA level of Foxp3 inside the mice lung affected with asthma while decrease that of IL-17A, IL-23, and RORγt. NF-κB pathway activation elicited by OVA was suppressed by Rbs inside the pulmonary tissues. Rbs played significantly in the reduction of airway inflammation induced by OVA which with modulating NF-κB pathway activation. PRACTICAL APPLICATIONS: Simultaneous therapy with medicine and food is strategically significant for disease prevention and treatment in traditional Chinese medicine. Rbs is a diterpene glycoside isolated from Rubus suavissimus. The anti-inflammatory and anti-asthmatic mechanism dependent of Rbs need further study clinically. The goal of current investigation is to explore the anti-inflammatory as well as anti-asthmatic activity of Rbs in mouse models of OVA-induced experimental allergic asthma. Results of the present study are scientifically supportive for the use of Rbs as an adjunctive reagent for clinical treatment of allergic asthma.

Effect of Tiotropium Bromide on Airway Inflammation and Programmed Cell Death 5 in a Mouse Model of Ovalbumin-Induced Allergic Asthma.

Rationale We previously demonstrated increased expression of programmed cell death 5 (PDCD5) in asthmatic patients and ovalbumin-induced allergic asthma. International guidelines (GINA 2019) have included the use of tiotropium bromide for chronic treatment of the most severe and frequently exacerbated asthma in patients ≥6 years old, who do not have good response to inhaled corticosteroids. Objective To explore the role of tiotropium and its effect on PDCD5 level in a mouse model of chronic asthma. Methods We divided 12 female mice into 2 groups: untreated asthma (n = 6) and tiotropium-treated asthma (n = 6). The impact of tiotropium was assessed by histology of lung tissue and morphometry. Pulmonary function was tested by using pressure sensors. The number of cells in bronchoalveolar lavage fluid (BALF) was detected. Levels of PDCD5, active caspase-3, and muscarinic acetylcholine receptors M2 (ChRM2) and M3 (ChRM3) were examined. Results Tiotropium treatment significantly reduced airway inflammation and remodeling in asthmatic mice and intensified the lung function. PDCD5 level was reduced with tiotropium (p < 0.05). Moreover, active caspase-3 level was decreased with tiotropium (p < 0.001), and ChRM3 level was increased. Conclusions Tiotropium treatment may alleviate the pathological changes with asthma by regulating apoptosis.

Immunomodulatory and Anti-Inflammatory Potential of Curcumin for the Treatment of Allergic Asthma: Effects on Expression Levels of Pro-inflammatory Cytokines and Aquaporins.

Curcumin is well known for possessing anti-inflammatory properties and for its beneficial effects in the treatment of asthma. Current study investigates the immunomodulatory and anti-inflammatory effects of curcumin using mouse model of ovalbumin-induced allergic asthma. BALB/c mice were immunized with ovalbumin on day 0 and 14 to induce allergic asthma. Animals were treated with two different doses of curcumin (20mg/kg and 100mg/kg) and methylprednisolone from day 21 to 28. Mice were also daily challenged intranasally with ovalbumin during treatment period, and all groups were sacrificed at day 28. Histopathological examination showed amelioration of allergic asthma in treated groups as evident by the attenuation of infiltration of inflammatory cells, goblet cell hyperplasia, alveolar thickening, and edema and vascular congestion. Curcumin significantly reduced total and differential leukocyte counts in both bronchoalveolar lavage fluid and blood. Reverse transcription polymerase chain reaction analysis showed significantly suppressed mRNA expression levels of IL-4 and IL-5 (pro-inflammatory cytokines), TNF-α, TGF-β (pro-fibrotic cytokines), eotaxin (chemokine), and heat shock protein 70 (marker of airway obstruction) in treated groups. Attenuation of these pro-inflammatory markers might have led to the suppression of airway inflammation. The expression levels of aquaporin-1 (AQP) and AQP-5 were found significantly elevated in experimental groups which might be responsible for reduction of pulmonary edema. In conclusion, curcumin significantly ameliorated allergic asthma. The anti-asthmatic effect might be attributed to the suppression of pro-inflammatory cytokines, and elevation of aquaporin expression levels, suggesting further studies and clinical trials to establish its candidature in the treatment of allergic asthma.

Total glucosides of peony improve ovalbumin-induced allergic asthma by inhibiting mast cell degranulation

Paeonia lactiflora Pall. (peony) is a medicinal plant used in the Xiaoqinglong decoction, a commonly prescribed traditional Chinese medicine for asthma. The main active ingredients of peony roots-described as the total glucosides of peony (TGP)-have anti-inflammatory, immunomodulatory, and protective effects on endothelial cells, and they are known to improve rheumatoid arthritis. This study explored the underlying mechanism of TGP activity in the treatment of allergic asthma. Allergic asthma was induced in BALB/c mice by administering injections of ovalbumin (OVA) mixed with aluminum hydroxide gel and inhaling nebulized OVA. The OVA-sensitized mice were treated with TGP by oral gavage, and the potentially anti-asthmatic treatment effect was studied by testing airway hyperresponsiveness, classifying and counting of leukocytes, performing cytokine assays, and analyzing the lung histopathology. The β-hexosaminidase activity was assayed as a biomarker to evaluate the effect of TGP on mast cell degranulation. The mechanism of TGP was explored by monitoring the Ca2+ influx level in mast cells (RBL-2H3) using a Ca2+ fluorescent probe technique. In mice with OVA-induced allergic asthma, TGP reduced airway hyperresponsiveness and improved lung tissue pathology, which included a decrease in inflammatory cell infiltration and collagen deposition. TGP also significantly lowered BALF leukocyte, eosinophil, and neutrophil counts, along with chemokines and cytokines, such as eotaxin, TNF-α, IL-4, and MIP-1α, in serum and lungs of OVA-challenged mice. These effects were further confirmed with the decrease of β-hexosaminidase release and the inhibition of Ca2+ influx in mast cell degranulation. Our findings suggest that TGP improved OVA-induced allergic asthma in mice mainly by suppressing Ca2+ influx-dependent mast cell degranulation.

A Novel Oral Glutarimide Derivative XC8 Suppresses Sephadex-Induced Lung Inflammation in Rats and Ovalbumin-induced Acute and Chronic Asthma in Guinea Pigs.

Corticosteroids are the preferred option to treat asthma, however, they possess serious side effects and are inefficient in 10% of patients. Thus, new therapeutic approaches for asthma treatment are required. To study the efficacy of a novel glutarimide derivative XC8 in a Sephadex-induced lung inflammation in rats as well as in acute and chronic ovalbumin-induced allergic asthma in guinea pigs. Rats were treated with 0.18-18 mg/kg of XC8 intragastrically 4 times (24 h and 1 h prior to and 24 h and 45 h after endotracheal administration of Sephadex). The number of inflammatory cells in bronchoalveaolar lavages (BAL) was determined. Guinea pigs were treated with 0.045 -1.4 mg/kg (acute asthma) or with 1.4 and 7.0 mg/kg of XC8 (chronic asthma) intragastrically following the sensitization with ovalbumin and during aerosol challenge. Lung inflammation, numbers of eosinophils (BAL and lung tissue), goblet cells, degranulating mast cells and specific airway resistance (sRAW) were determined. The comparator steroid drug budesonide (0.5 mg/kg for rats and 0.16 mg/kg for guinea pigs) was administered by inhalation. XC8 reduced influx of eosinophils into BAL in Sephadex-induced lung inflammation model in rats (by 2.6-6.4 times). Treatment of acute asthma in guinea pigs significantly reduced eosinophils in guinea pigs in BAL (from 55% to 30%-39% of the total cell count) and goblet cells in lung tissue. In a model of acute and chronic asthma, XC8 reduced significantly the number of eosinophils and degranulating mast cells in the lung tissue. Treatment with XC8 but not with budesonide decreased the specific airway resistance in acute and chronic asthma model up to the level of naive animals. XC8 induced a profound anti-inflammatory effect by reducing eosinophils in BAL and eosinophils and degranulating mast cell numbers in the airway tissue. The anti-asthmatic effect of XC8 is comparable to that of budesonide. Moreover, in contrast to budesonide, XC8 was capable to reduce goblet cells and airway resistance.

Therapeutic Potential of Morin in Ovalbumin-induced Allergic Asthma Via Modulation of SUMF2/IL-13 and BLT2/NF-kB Signaling Pathway.

Allergic asthma is a chronic immune-inflammatory disorder, characterized by airway inflammation and airway hyperresponsiveness (AHR). Morin is a natural flavonoid reported to exhibit inhibitory action against IgE-mediated allergic response. To determine the efficacy of murine model of ovalbumin (OVA)-induced AHR inhibition by morin and decipher the molecular mechanism involved. Sprague-Dawley rats were sensitized and challenged with OVA to induce AHR. Rats received treatment with morin (10, 30 and 100 mg/kg, p.o.) for the next 28 days. Morin (30 and 100 mg/kg) significantly and dose-dependently attenuated (p < 0.01 and p < 0.001) OVA-induced alterations in pulse oxy and lung function test, increased bronchoalveolar lavage fluid cell counts, elevated total protein and albumin levels in serum, BALF, and lungs, increased serum total and OVA-specific IgE levels and, elevated oxidative stress levels in the lung. RT-PCR analysis revealed that morin treatment (30 and 100 mg/kg) significantly (p < 0.001) up-regulated SUMF2 mRNA expression in lungs whereas mRNA expressions of BLT2, NF-κB, and Th2-cytokine (TNF-α, IL-1β, IL-4, IL-6, and IL-13) were down-regulated significantly and dose-dependently (p < 0.01 and p < 0.001). Also, histologic and ultrastructural studies showed that morin significantly inhibited (p < 0.001) OVAinduced perivascular and peribranchial inflammatory infiltration and interstitial fibrosis. Morin exhibited inhibitory effect against OVA-induced allergic asthma by activation of SUMF2 which impeded IL-13 expression and in turn attenuated Th2-cytokines, BLT2, NF-κB, and IgE levels to ameliorate AHR. Thus, our findings suggested that morin could be considered as a potential alternative therapeutic agent for the management of allergic asthma.

Suppressive effects of type I angiotensin receptor antagonists, candesartan and irbesartan on allergic asthma

The effects of candesartan and irbesartan, antagonists of the type I angiotensin II receptor, were investigated on allergic asthma. The antigen-induced degranulation was measured by evaluating β-hexosaminidase activity in vitro. Additionally, a murine ovalbumin-induced allergic asthma model was used to test the in vivo efficacy. It was observed that while candesartan inhibited the antigen-induced degranulation in rat RBL-2H3 mast cells, irbesartan did not. Administration of candesartan and irbesartan decreased the number of immune cells in the bronchoalveolar lavage fluid and reduced the expression of Th2 (IL-4, IL-5, and IL-13) and Th1 cytokines (IL-2 and IFN-γ) in the lung tissues of mice with ovalbumin-induced allergic asthma. Histological studies revealed that both antagonists reduced inflammation and mucin production in the lungs. Therefore, these findings provide evidence that candesartan and irbesartan could have potential applications as anti-allergic agents.

A role of mast cells in ovalbumin-induced mouse allergic asthma responses suppressed by natural product mixture (Hwangchango)

A role of mast cells in ovalbumin-induced mouse allergic asthma responses suppressed by natural product mixture (Hwangchango)

Comparative research of the curative effects of pinelliae rhizoma and pinelliae rhizoma praeparatum cum alumine on ovalbumin-induced allergic asthma in rats

Aim: This study was designed to compare the curative effects of Pinelliae Rhizoma (RPT) and Pinelliae Rhizoma Praeparatum cum Alumine (QPT) on ovalbumin (OVA)-induced allergic asthma in rats. Materials and Methods: Asthmatic rats were prepared by intraperitoneal injection and inhalation of OVA, and RPT and QPT at the doses of 120 and 240 mg/kg/day were administered orally for consecutive 7 days. Then, histopathological changes of the lung tissues were examined; levels of interleukin (IL)-4 and interferon (IFN)-γ in the bronchoalveolar lavage fluids (BALFs) and immunoglobulin (Ig) E in the serum were measured by enzyme-linked immunosorbent assay; eosinophils (EOS) in BALFs were also determined. Furthermore, the expressions of mucin 5AC (MUC5AC) and AQP-5 in the lung tissues were determined by quantitative real-time fluorogenic polymerase chain reaction and western blot assays. Besides, high-performance liquid chromatography-LTQ-Orbitrap-Elite-MS analysis was applied to compare the constituent's difference between the RPT and QPT. Results: The present results revealed that both the RPT and QPT have the potential curative effects for treating OVA-induced asthma in rats via inhibiting inflammatory reactions (suppressing EOS influx, IgE secretion, and release of IL-4 whereas increasing the release of IFN-γ) and modulating the mRNA and protein expressions of MUC5AC and AQP-5. In addition, our results also evidenced that QPT exhibited a better curative effect on allergic asthmatic rats compared to RPT. Conclusion: Our results are beneficial for confirming the traditional Chinese medicinal theory of “QPT is good at removing dampness to reduce phlegm.” Abbreviations used: BALF: Bronchoalveolar lavage fluid; ELISA: Enzyme-linked immunosorbent assay; EOS: Eosinophils; IFN: Interferon; IL: Interleukin; OVA: Ovalbumin; qRT-PCR: Quantitative real-time fluorogenic polymerase chain reaction; QPT: Rhizoma Pinelliae Praeparatum cum Alumine; RIPA: Radioimmunoprecipitation assay; RPT: Pinelliae Rhizoma; SDS-PAGE: Sodium dodecyl sulfate-polyacrylamide gel electrophoresis; TCM: Traditional Chinese medicine.

Resveratrol Attenuates Allergic Asthma and Associated Inflammation in the Lungs Through Regulation of miRNA-34a That Targets FoxP3 in Mice.

Asthma is a chronic inflammatory disease of airways mediated by T-helper 2 (Th2) cells involving complex signaling pathways. Although resveratrol has previously been shown to attenuate allergic asthma, the role of miRNA in this process has not been studied. We investigated the effect of resveratrol on ovalbumin-induced experimental allergic asthma in mice. To that end, BALB/c mice were immunized with ovalbumin (OVA) intraperitoneally followed by oral gavage of vehicle (OVA-veh) or resveratrol (100 mg/kg body) (OVA-res). On day 7, the experimental groups received intranasal challenge of OVA followed by 7 days of additional oral gavage of vehicle or resveratrol. At day 15, all mice were euthanized and bronchioalveolar fluid (BALF), serum and lung infiltrating cells were collected and analyzed. The data showed that resveratrol significantly reduced IL-5, IL-13, and TGF-β in the serum and BALF in mice with OVA-induced asthma. Also, we saw a decrease in CD3+CD4+, CD3+CD8+, and CD4+IL-4+ cells with increase in CD4+CD25+FOXP3+ cells in pulmonary inflammatory cell infiltrate in OVA-res group when compared to OVA-veh. miRNA expression arrays using lung infiltrating cells showed that resveratrol caused significant alterations in miRNA expression, specifically downregulating the expression of miR-34a. Additionally, miR-34a was found to target FOXP3, as evidenced by enhanced expression of FOXP3 in the lung tissue. Also, transfection studies showed that miR-34a inhibitor upregulated FOXP3 expression while miR-34a-mimic downregulated FOXP3 expression. The current study suggests that resveratrol attenuates allergic asthma by downregulating miR-34a that induces increased expression of FOXP3, a master regulator of Treg development and functions.

Anti-allergic effects of salvianolic acid A and tanshinone IIA from Salvia miltiorrhiza determined using in vivo and in vitro experiments

Salvia miltiorrhiza root has been used in Asian traditional medicine for the treatment of cardiovascular diseases, asthma, and other conditions. Salvianolic acid B from S. miltiorrhiza extracts has been shown to improve airway hyperresponsiveness. We investigated the effects of salvianolic acid A, tanshinone I, and tanshinone IIA from S. miltiorrhiza in allergic asthma by using rat RBL-2H3 mast cells and female Balb/c mice. Antigen-induced degranulation was assessed by measuring β-hexosaminidase activity in vitro. In addition, a murine ovalbumin-induced allergic asthma model was used to test the in vivo efficacy of salvianolic acid A and tanshinone IIA. Tanshinone I and tanshinone IIA inhibited antigen-induced degranulation of mast cells, but salvianolic acid A did not. Administration of salvianolic acid A and tanshinone IIA decreased the number of immune cells, particularly eosinophils in allergic asthma-induced mice. Histological studies showed that salvianolic acid A and tanshinone IIA reduced mucin production and inflammation in the lungs. Administration of salvianolic acid A and tanshinone IIA reduced the expression and secretion of Th2 cytokines (IL-4 and IL-13) in the bronchoalveolar lavage fluid and lung tissues of mice with ovalbumin-induced allergic asthma. These findings provide evidence that salvianolic acid A and tanshinone IIA may be potential anti-allergic therapeutics.