Abstract

Gumiganghwal-tang is a traditional herbal prescription that is used widely for the treatment of the common cold and inflammatory diseases in Korea and other Asian countries. In this study, we investigated the protective effects of a Gumiganghwal-tang aqueous extract (GGTA) against airway inflammation and pulmonary fibrosis using a mouse model of chronic asthma. Chronic asthma was modeled in BALB/c mice via sensitization/challenge with an intraperitoneal injection of 1% ovalbumin (OVA) and inhalation of nebulized 1% OVA for 4 weeks. GGTA (100 mg/kg or 200 mg/kg) was also administered by oral gavage once a day for 4 weeks. We investigated the number of inflammatory cells, production of T-helper type 2 (Th2) cytokines, chemokine and the total transforming growth factor-β1 (TGF-β1) in bronchoalveolar lavage fluid (BALF); the levels of immunoglobulin E (IgE) in the plasma; the infiltration of inflammatory cells in lung tissue; and the expression of TGF-β1, Smad-3, and collagen in lung tissue. Our results revealed that GGTA lowered the recruitment of inflammatory cells (particularly, lymphocyte); and decreased the production of Th2 cytokines, chemokine and total TGF-β1; and attenuated the levels of total and OVA-specific IgE; and decreased the infiltration of inflammatory cells. Moreover, GGTA significantly reduced the expression of TGF-β1 and Smad-3, and lowered collagen deposition. These results indicate that GGTA reduces airway inflammation and pulmonary fibrosis by regulating Th2 cytokines production and the TGF-β1/Smad-3 pathway, thus providing a potential treatment for chronic asthma.

Highlights

  • Allergic asthma is a chronic inflammatory disease of the lung associated with excessive airway infiltration of inflammatory cells into lung tissues, elevated levels of allergen-specific immunoglobulinPLOS ONE | DOI:10.1371/journal.pone.0164833 October 14, 2016Gumiganghwal-tang Reduces Pulmonary Fibrosis by transforming growth factor-β1 (TGF-β1)/Smad Signaling Pathway in Chronic AsthmaE (IgE), overexpression of T-helper type 2 (Th2) cytokines and chemokine including IL-4, IL-5, IL13, and eotaxin [1]

  • To determine whether Gumiganghwal-tang aqueous extract (GGTA) influenced Th2 cytokines and chemokine production into bronchoalveolar lavage fluid (BALF), we evaluated the levels of IL-4, IL-5, IL-13, and eotaxin in BALF

  • Our findings indicated that GGTA attenuated the accumulation of inflammatory cells into airway and lung tissue, with decreased production of Th2 cytokines, chemokine, total TGF-β1 and, total and OVA-specific immunoglobulin E (IgE)

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Summary

Introduction

Allergic asthma is a chronic inflammatory disease of the lung associated with excessive airway infiltration of inflammatory cells into lung tissues, elevated levels of allergen-specific immunoglobulinPLOS ONE | DOI:10.1371/journal.pone.0164833 October 14, 2016Gumiganghwal-tang Reduces Pulmonary Fibrosis by TGF-β1/Smad Signaling Pathway in Chronic AsthmaE (IgE), overexpression of T-helper type 2 (Th2) cytokines and chemokine including IL-4, IL-5, IL13, and eotaxin [1]. Gumiganghwal-tang Reduces Pulmonary Fibrosis by TGF-β1/Smad Signaling Pathway in Chronic Asthma. Chronic asthma spanning over a long period is characterized by pulmonary inflammation, subepithelial/peribranchial fibrosis, and collagen deposition [2]. Th2-type cytokines, which are secreted by Th2 cells, play a central role in the pathogenesis of allergic asthma by regulating IgE production, the release of a variety of inflammatory mediators, and the differentiation and activation of eosinophils [3]. Smads are key proteins that are recognized as a major pathway of TGF-β1 signaling in progressive renal fibrosis [6]. According to a previous study, the TGF-β1/Smad signaling pathway is one of the important mechanisms involved in the development of asthma [9]

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