Abstract
Macmoondongtang has been used as a traditional medicine to treat pulmonary disease in Korea. However, the mechanism underlying its therapeutic effect has yet to be reported. In the present study, the role of macmoondongtang as a respiratory medicine, especially as an anti-asthmatic agent, has been attributed to the down-regulation of interleukin (IL)-4 and tumor necrosis factor (TNF)-α. BALB/c mice were divided into five groups: control, asthma-induced control, dexamethasone treatment, treatment with 150 mg/kg macmoondongtang, and treatment with 1500 mg/kg macmoondongtang. To evaluate the anti-asthmatic effect of macmoondongtang, we investigated its suppressive or inhibitory effects against typical asthmatic changes such as differential cell count in bronchioalveolar fluid (BALF), serum IgE levels, lung morphology, expression of Th1/Th2 cell transcription factors such as T-bet and GATA-3, and Th1-/Th2-/Th17-related cytokines such as interferon (IFN)-γ, IL-12p40, IL-4, -5, -13, TNF-α, and IL-6. The active ingredients in macmoondongtang were further analyzed. Macmoondongtang treatment down-regulated serum IgE level, a very important marker of hyper-responsiveness. It reversed typical morphological changes such as mucous hypersecretion, lung epithelial cell hyperplasia, and inflammatory cell infiltration near bronchioalveolar space and veins. Macmoondongtang significantly decreased neutrophil count in BALF, as well as reduced T-bet, IFN-γ, and TNF-α expression in the lung. It also showed a dose-dependent control of inflammatory cells in BALF, controlled the expression of IL-12, IL-4, and IL-5 genes in the lung, and the protein expression of IL12p40, GATA-3, IL-4, IL-5, and IL-13. The component analysis revealed glycyrrhizin and liquiritin as the active ingredients. Macmoondongtang treatment alleviates asthma symptoms and modulate the Th1-/Th2- related cytokines. Glycyrrhizin and liquiritin could be the major the active therapeutic components.
Highlights
In 2013, the World Health Organization reported that at least 200 million individuals worldwide were diagnosed with asthma
Macmoondongtang significantly decreased neutrophil count in bronchioalveolar fluid (BALF), as well as reduced T-bet, IFN-γ, and tumor necrosis factor (TNF)-α expression in the lung
IL-4 is induced by GATA-3, a transcription factor with several bioactive functions, including stimulation of Th2-related cytokine expression [9], regulation of IgE levels [10], and so on
Summary
In 2013, the World Health Organization reported that at least 200 million individuals worldwide were diagnosed with asthma. Among several theories of asthma occurrence, the imbalance between Th1 and Th2 cells plays a significant role in increasing the risk [2]. Cytokines such as interferon gamma (IFN-γ) that induce the release of Th1 cells are associated with the severity of asthma [4]. As one of the important factors that regulate asthma severity, IL-6 induces IL-4 up-regulation and stimulates Th17 cell differentiation [12]. TNF-α is synthesized by macrophages [17] It recruits neutrophils and eosinophils [18], stimulates T cell activation [19], and establishes airway hyperresponsiveness [20]
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