Inhibitory effects of astragaloside IV on ovalbumin-induced chronic experimental asthma

Astragaloside IV, a new cycloartane-type triterpene glycoside extract of Astragalus membranaceus Bunge, has been identified for its potent immunoregulatory, antiinflammatory, and antifibrotic actions. Here we investigated whether astragaloside IV could suppress the progression of airway inflammation, airway hyperresponsiveness, and airway remodeling in a murine model of chronic asthma. BALB/c mice sensitized to ovalbumin (OVA) were chronically challenged with aerosolized OVA for 8 weeks. Astragaloside IV was orally administered at a dose of 50 mg·kg–1·day–1 during each OVA challenge. Astragaloside IV treatment resulted in significant reduction of eosinophilic airway inflammation, airway hyperresponsiveness, interleukin (IL)-4 and IL-13 levels in bronchoalveolar lavage fluid, and total immunoglobulin E levels in serum. Furthermore, astragaloside IV treatment markedly inhibited airway remodeling, including subepithelial fibrosis, smooth muscle hypertrophy, and goblet cell hyperplasia. In addition, the expression of transforming growth factor-β1 in the lung was also reduced by astragaloside IV. These data indicate that astragaloside IV may mitigate the development of characteristic features in chronic experimental asthma.

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VIWITHAN: A STANDARDIZED ASHWAGANDHA EXTRACT AMELIORATES OVALBUMININDUCED AIRWAY-INFLAMMATION AND OXIDATIVE STRESS IN MOUSE MODEL

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2021.v14i3.40119 ◽

2021 ◽

pp. 89-93

Author(s):

VASAVI HS ◽

SUDEEP HV ◽

RAMANAIAH ILLURI ◽

SHYAMPRASAD K

Keyword(s):

Oxidative Stress ◽

Airway Inflammation ◽

Transforming Growth Factor ◽

Lavage Fluid ◽

Interleukin 10 ◽

Transforming Growth Factor Β1 ◽

Lung Pathology ◽

Protective Effects ◽

Lung Weight ◽

And Oxidative Stress

Objective: Withania somnifera, commonly known as Ashwagandha, Indian ginseng, has been used in Ayurvedic and indigenous medicinal preparations for various disease conditions since long time. In the present study, we investigated the protective effects of Viwithan, a standardized proprietary extract from Ashwagandha roots, against airway-inflammation and oxidative stress modulation in an ovalbumin (OVA)-induced murine model of inflammation. Methods: Allergic asthma was initiated in BALB/c mice by sensitizing with OVA on days 1 and 14, followed by intranasal challenge with OVA on days 27, 28, and 29. Mice were administered Viwithan (200 and 400 mg/kg) by oral gavage before challenge. Then, mice were evaluated for the presence of airway inflammation, production of allergen-specific cytokine response, lung pathology, and oxidative stress modulation. Results: The results showed that treatment with Viwithan attenuated OVA-induced lung inflammation in mice. Viwithan significantly attenuated inflammatory cell infiltration into the bronchoalveolar lavage fluid and markedly reduced the levels of pro-inflammatory cytokines, interleukin-10, and transforming growth factor-β1 in lung tissues. Viwithan treatment considerably reduced the lung weight in OVA-sensitized mice. Viwithan markedly attenuated the OVA-induced generation of reactive oxygen species in lung tissues. Conclusion: Together, these results suggested that Viwithan alleviates OVA-induced airway-inflammation and oxidative stress, highlighting the potential of standardized Ashwagandha extract as a useful therapeutic agent for pulmonary fibrosis management.

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Proanthocyanidin from Grape Seed Extract Inhibits Airway Inflammation and Remodeling in a Murine Model of Chronic Asthma

Natural Product Communications ◽

10.1177/1934578x1501000210 ◽

2015 ◽

Vol 10 (2) ◽

pp. 1934578X1501000 ◽

Cited By ~ 4

Author(s):

Dan-Yang Zhou ◽

Su-Rong Fang ◽

Chun-Fang Zou ◽

Qian Zhang ◽

Wei Gu

Keyword(s):

Growth Factor ◽

Airway Inflammation ◽

Murine Model ◽

Transforming Growth Factor ◽

Immunoglobulin E ◽

Airway Remodeling ◽

Grape Seed ◽

Total Serum ◽

Chronic Asthma ◽

Tgf Β1

Asthma is characterized by airway inflammation and airway remodeling. Our previous study revealed that grape seed proanthocyanidin extract (GSPE) could inhibit asthmatic airway inflammation and airway hyper-responsiveness by down-regulation of inducible nitric oxide synthase in a murine model of acute asthma. The present study aimed to evaluate GSPE's effects on airway inflammation and airway remodeling in a chronic asthmatic model. BALB/c mice were sensitized with ovalbumin (OVA) and then were challenged three times a week for 8 weeks. Airway responsiveness was measured at 24 h after the last OVA challenge. HE staining, PAS staining, and Masson staining were used to observe any airway inflammation in the lung tissue, airway mucus secretion, and subepithelial fibrosis, respectively. The cytokines levels in the lavage fluid (BALF) in addition to the total serum immunoglobulin E (IgE) levels were detected by ELISA. Furthermore, lung collagen contents, α-smooth muscle actin (α-SMA), and transforming growth factor-β1 (TGF-β1) expression in the airway were assessed by hydroxyproline assay, immunohistochemistry, andWestern blot analysis, respectively. GSPE administration significantly suppressed airway resistance as well as reduced the amount of inflammatory cells, especially the eosinophil count, in BALF. Additionally, the GSPE treatment markedly decreased interleukin (IL)-4, IL-13, and vascular endothelial growth factor (VEGF) levels in BALF in addition to the total serum IgE levels. A histological examination demonstrated that GSPE significantly ameliorated allergen-induced lung eosinophilic inflammation and decreased PAS-positive epithelial cells in the airway. The elevated hydroxyproline contents, lung α-SMA contents, and TGF-β1 protein expression that were observed in the OVA mice were also inhibited by GSPE. In conclusion, GSPE could inhibit airway inflammation and airway remodeling in a murine model of chronic asthma, thus providing a potential treatment for asthma.

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Lignosus rhinocerotis Cooke Ryvarden ameliorates airway inflammation, mucus hypersecretion and airway hyperresponsiveness in a murine model of asthma

PLoS ONE ◽

10.1371/journal.pone.0249091 ◽

2021 ◽

Vol 16 (3) ◽

pp. e0249091

Author(s):

Malagobadan Johnathan ◽

Siti Aminah Muhamad ◽

Siew Hua Gan ◽

Johnson Stanslas ◽

Wan Ezumi Mohd Fuad ◽

...

Keyword(s):

Airway Inflammation ◽

Airway Hyperresponsiveness ◽

Therapeutic Potential ◽

Indigenous Communities ◽

Lavage Fluid ◽

Hot Water ◽

Sprague Dawley ◽

Cell Hyperplasia ◽

Mucus Hypersecretion ◽

Lignosus Rhinocerotis

Lignosus rhinocerotis Cooke. (L. rhinocerotis) is a medicinal mushroom traditionally used in the treatment of asthma and several other diseases by the indigenous communities in Malaysia. In this study, the effects of L. rhinocerotis on allergic airway inflammation and hyperresponsiveness were investigated. L. rhinocerotis extract (LRE) was prepared by hot water extraction using soxhlet. Airway hyperresponsiveness (AHR) study was performed in house dust mite (HDM)-induced asthma in Balb/c mice while airway inflammation study was performed in ovalbumin (OVA)-induced asthma in Sprague-Dawley rats. Treatment with different doses of LRE (125, 250 and 500 mg/kg) significantly inhibited AHR in HDM-induced mice. Treatment with LRE also significantly decreased the elevated IgE in serum, Th2 cytokines in bronchoalveolar lavage fluid and ameliorated OVA-induced histological changes in rats by attenuating leukocyte infiltration, mucus hypersecretion and goblet cell hyperplasia in the lungs. LRE also significantly reduced the number of eosinophils and neutrophils in BALF. Interestingly, a significant reduction of the FOXP3+ regulatory T lymphocytes was observed following OVA induction, but the cells were significantly elevated with LRE treatment. Subsequent analyses on gene expression revealed regulation of several important genes i.e. IL17A, ADAM33, CCL5, IL4, CCR3, CCR8, PMCH, CCL22, IFNG, CCL17, CCR4, PRG2, FCER1A, CLCA1, CHIA and Cma1 which were up-regulated following OVA induction but down-regulated following treatment with LRE. In conclusion, LRE alleviates allergy airway inflammation and hyperresponsiveness, thus suggesting its therapeutic potential as a new armamentarium against allergic asthma.

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Targeted inhibition of β-catenin alleviates airway inflammation and remodeling in asthma via modulating the profibrotic and anti-inflammatory actions of transforming growth factor-β1

10.21203/rs.3.rs-32854/v1 ◽

2020 ◽

Author(s):

Rujie Huo ◽

Xinli Tian ◽

Qin Chang ◽

Dai Liu ◽

Chen Wang ◽

...

Keyword(s):

Airway Inflammation ◽

Transforming Growth Factor ◽

Cell Model ◽

Airway Remodeling ◽

Inhibitory Effect ◽

Transforming Growth Factor Β1 ◽

Alveolar Type ◽

Anti Inflammatory ◽

Targeted Inhibition ◽

Tgf Β1

Abstract Background and objective TGF-β1 is a key cytokine involved in airway inflammation and airway remodeling in asthma, owing to its anti-inflammatory and profibrotic effects. In our previous study, we found that the knockdown of cytosolic β-catenin mitigated the profibrogenic effect of TGF-β1 without affecting its anti-inflammatory effect. However, the exact role of targeting β-catenin in asthma is not yet fully demonstrated. In the present study, we investigated the effect and mechanism of targeting β-catenin in OVA-challenged asthmatic rats with airway inflammation and remodeling features. Methods We integrated experimental asthma model and asthma related cell model to explore the effect of targeting β-catenin on airway inflammation and remodeling of asthma. Results Blocking β-catenin with ICG001, a small molecule inhibitor of β-catenin/TCF via binding to CBP, attenuated airway inflammation by increasing the level of the anti-inflammatory cytokines IL-10, IL-35, and reducing the level of proinflammation cytokine IL-17. Suppressing β-catenin with ICG001 has an inhibitory effect on airway remodeling via reducing the level of TGF-β1 and the expression of MMP-7 and Snail, upregulating expression of E-cadherin, downregulating expressions of α-SMA and Fn. Inhibiting β-catenin with ICG001 suppressed TGF-β1-induced proliferation and activation of lung fibroblast (CCC-REPF-1) cells, and blocked TGF-β1-induced, blocked TGF-β1 induced EMT of alveolar type II epithelial (RLE-6TN) cells. Conclusions Blockade of β-catenin/TCF not only prevents TGF-β1 induced EMT and profibrogenic effects involved in pathological remodeling of airway, but also alleviates airway inflammation in asthma by balancing proinflammatory and anti-inflammatory cytokine.

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Relaxin Reverses Airway Remodeling and Airway Dysfunction in Allergic Airways Disease

Endocrinology ◽

10.1210/en.2008-1457 ◽

2009 ◽

Vol 150 (6) ◽

pp. 2692-2699 ◽

Cited By ~ 27

Author(s):

Simon G. Royce ◽

Yu R. Miao ◽

Melissa Lee ◽

Chrishan S. Samuel ◽

Geoffrey W. Tregear ◽

...

Keyword(s):

Mouse Model ◽

Airway Inflammation ◽

Airway Hyperresponsiveness ◽

Structural Changes ◽

Airway Remodeling ◽

Vehicle Control ◽

Matrix Metalloproteinase 2 ◽

Collagen Deposition ◽

Cell Hyperplasia ◽

Novel Treatment

Mice deficient in the antifibrotic hormone relaxin develop structural changes in the airway that resemble airway remodeling, and demonstrate exaggerated remodeling changes in models of allergic airways disease (AAD). Relaxin expression in asthma has not been previously studied. We evaluated the efficacy of relaxin in the treatment of established airway remodeling in a mouse model of AAD. Relaxin expression in mouse AAD was also examined by immunohistochemistry and real-time PCR. BALB/c mice with established AAD were treated with relaxin or vehicle control (sc for 14 d), and effects on airway remodeling, airway inflammation, and airway hyperresponsiveness (AHR) were assessed. Relaxin expression was significantly reduced in the airways of mice with AAD compared with controls. Recombinant relaxin treatment in a mouse model of AAD reversed collagen deposition and epithelial thickening, and significantly improved AHR (all P < 0.05 vs. vehicle control), but did not influence airway inflammation or goblet cell hyperplasia. Relaxin treatment was associated with increased matrix metalloproteinase-2 levels, suggesting a possible mechanism for its antifibrotic effects. Endogenous relaxin expression is decreased in murine AAD, whereas exogenous relaxin represents a novel treatment capable of reversing established airway remodeling and AHR.

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Targeted inhibition of β-catenin alleviates airway inflammation and remodeling in asthma via modulating the profibrotic and anti-inflammatory actions of transforming growth factor-β1

Therapeutic Advances in Respiratory Disease ◽

10.1177/1753466620981858 ◽

2021 ◽

Vol 15 ◽

pp. 175346662098185

Author(s):

Rujie Huo ◽

Xinli Tian ◽

Qin Chang ◽

Dai Liu ◽

Chen Wang ◽

...

Keyword(s):

Airway Inflammation ◽

Transforming Growth Factor ◽

Epithelial Mesenchymal Transition ◽

Cell Model ◽

Airway Remodeling ◽

Transforming Growth Factor Β1 ◽

Mesenchymal Transition ◽

Molecule Inhibitor ◽

Anti Inflammatory ◽

Targeted Inhibition

Background: TGF-β1 is a key cytokine involved in both airway inflammation and airway remodeling in asthma because of its anti-inflammatory and profibrotic effect. In our previous study, we found that knockdown of cytosolic β-catenin alleviated the profibrogenic effect of TGF-β1 without influencing its anti-inflammatory effect. However, the exact role of targeting β-catenin in asthma is not yet fully demonstrated. In the present study, we investigated the effect and mechanism of targeting β-catenin in OVA-challenged asthmatic rats with airway inflammation and remodeling features. Methods: We integrated experimental asthma model and asthma related cell model to explore the effect of targeting β-catenin on airway inflammation and remodeling of asthma. Results: Blocking β-catenin with ICG001, a small molecule inhibitor of β-catenin/TCF via binding to cAMP-response elementbinding protein, attenuated airway inflammation by increasing levels of anti-inflammation cytokines IL-10, IL-35 and decreasing levels of T helper (Th)2 cells and Th17 cytokine. Suppressing β-catenin by ICG001 inhibited airway remodeling via reducing the level of TGF-β1 and the expressions of Snail, MMP-7, MMP-9 and, up-regulating expression of E-cadherin, down-regulating expressions of α-SMA and Fn. Inhibition of β-catenin with ICG001 suppressed TGF-β1 induced proliferation and activation of CCC-REPF-1, blocked TGF-β1 induced epithelial–mesenchymal transition (EMT) of RLE-6TN. Conclusion: Blockade of β-catenin/TCF not only prevents TGF-β1 induced EMT and profibrogenic effects involved in pathological remodeling of airway, but also alleviates airway inflammation in asthma by balancing pro-inflammatory and anti-inflammatory cytokine. In conclusion, targeting β-catenin specifically via inhibition of β-catenin/TCF might be a new therapeutic strategy for asthma. The reviews of this paper are available via the supplemental material section.

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FSTL1 aggravates cigarette smoke-induced airway inflammation and airway remodeling by regulating autophagy

BMC Pulmonary Medicine ◽

10.1186/s12890-021-01409-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ying Liu ◽

Jiawei Xu ◽

Tian Liu ◽

Jinxiang Wu ◽

Jiping Zhao ◽

...

Keyword(s):

Lung Function ◽

Airway Inflammation ◽

Cigarette Smoke ◽

Airway Remodeling ◽

Critical Factor ◽

Lavage Fluid ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Copd Patients ◽

Impaired Lung Function

Abstract Background Cigarette smoke (CS) is a major risk factor for Chronic Obstructive Pulmonary Disease (COPD). Follistatin-like protein 1 (FSTL1), a critical factor during embryogenesis particularly in respiratory lung development, is a novel mediator related to inflammation and tissue remodeling. We tried to investigate the role of FSTL1 in CS-induced autophagy dysregulation, airway inflammation and remodeling. Methods Serum and lung specimens were obtained from COPD patients and controls. Adult female wild-type (WT) mice, FSTL1± mice and FSTL1flox/+ mice were exposed to room air or chronic CS. Additionally, 3-methyladenine (3-MA), an inhibitor of autophagy, was applied in CS-exposed WT mice. The lung tissues and serum from patients and murine models were tested for FSTL1 and autophagy-associated protein expression by ELISA, western blotting and immunohistochemical. Autophagosome were observed using electron microscope technology. LTB4, IL-8 and TNF-α in bronchoalveolar lavage fluid of mice were examined using ELISA. Airway remodeling and lung function were also assessed. Results Both FSTL1 and autophagy biomarkers increased in COPD patients and CS-exposed WT mice. Autophagy activation was upregulated in CS-exposed mice accompanied by airway remodeling and airway inflammation. FSTL1± mice showed a lower level of CS-induced autophagy compared with the control mice. FSTL1± mice can also resist CS-induced inflammatory response, airway remodeling and impaired lung function. CS-exposed WT mice with 3-MA pretreatment have a similar manifestation with CS-exposed FSTL1± mice. Conclusions FSTL1 promotes CS-induced COPD by modulating autophagy, therefore targeting FSTL1 and autophagy may shed light on treating cigarette smoke-induced COPD.

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Transforming growth factor-β1 induces bronchial epithelial cells to mesenchymal transition by activating the Snail pathway and promotes airway remodeling in asthma

Molecular Medicine Reports ◽

10.3892/mmr.2013.1728 ◽

2013 ◽

Vol 8 (6) ◽

pp. 1663-1668 ◽

Cited By ~ 36

Author(s):

ZHAO-CHUAN YANG ◽

MING-JI YI ◽

NI RAN ◽

CHONG WANG ◽

PENG FU ◽

...

Keyword(s):

Growth Factor ◽

Epithelial Cells ◽

Transforming Growth Factor ◽

Airway Remodeling ◽

Transforming Growth Factor Β1 ◽

Bronchial Epithelial Cells ◽

Bronchial Epithelial ◽

Mesenchymal Transition

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Paeonol attenuates airway inflammation and hyperresponsiveness in a murine model of ovalbumin-induced asthma

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y10-077 ◽

2010 ◽

Vol 88 (10) ◽

pp. 1010-1016 ◽

Cited By ~ 20

Author(s):

Qiang Du ◽

Gan-Zhu Feng ◽

Li Shen ◽

Jin Cui ◽

Jian-Kang Cai

Keyword(s):

Bronchoalveolar Lavage ◽

Airway Inflammation ◽

Bronchoalveolar Lavage Fluid ◽

Immunoglobulin E ◽

Therapeutic Potential ◽

Lavage Fluid ◽

Interleukin 4 ◽

Moutan Cortex ◽

Ifn Γ ◽

Anti Inflammatory

Paeonol, the main active component isolated from Moutan Cortex, possesses extensive pharmacological activities such as anti-inflammatory, anti-allergic, and immunoregulatory effects. In the present study, we examined the effects of paeonol on airway inflammation and hyperresponsiveness in a mouse model of allergic asthma. BALB/c mice sensitized and challenged with ovalbumin were administered paeonol intragastrically at a dose of 100 mg/kg daily. Paeonol significantly suppressed ovalbumin-induced airway hyperresponsiveness to acetylcholine chloride. Paeonol administration significantly inhibited the total inflammatory cell and eosinophil count in bronchoalveolar lavage fluid. Treatment with paeonol significantly enhanced IFN-γ levels and decreased interleukin-4 and interleukin-13 levels in bronchoalveolar lavage fluid and total immunoglobulin E levels in serum. Histological examination of lung tissue demonstrated that paeonol significantly attenuated allergen-induced lung eosinophilic inflammation and mucus-producing goblet cells in the airway. These data suggest that paeonol exhibits anti-inflammatory activity in allergic mice and may possess new therapeutic potential for the treatment of allergic bronchial asthma.

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