Macmoondongtang modulates Th1-/Th2-related cytokines and alleviates asthma in a murine model

• Published in: PloS one Vol. 14; no. 12; p. e0224517
• Main Authors: Lee, Soon-Young, Kang, Bossng, Bok, So-Hyeon, Cho, Seung Sik, Park, Dae-Hun
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 02.12.2019; Public Library of Science (PLoS)
• Subjects: Allergies; Analysis; Animal models; Animals; Asthma; Asthma - drug therapy; Asthma - immunology; Biological response modifiers; Biology and Life Sciences; Bronchoalveolar Lavage; Cytokines; Cytokines - metabolism; Cytology; Dexamethasone; Disease Models, Animal; DNA binding proteins; DNA methylation; Dose-Response Relationship, Drug; Drug dosages; Epithelial cells; Female; GATA-3 protein; Gene expression; Gene Expression Regulation - drug effects; Genes; Glucocorticoids; Glycyrrhizin; Health aspects; Helper cells; Hyperplasia; Immunoglobulin E; Inflammation; Ingredients; Interferon; Interleukin; Interleukin 1; Interleukin 12; Interleukin 13; Interleukin 4; Interleukin 5; Interleukin 6; Interleukins; Lung diseases; Lung morphology; Lymphocytes T; Medicine; Medicine and Health Sciences; Metastases; Mice; Mice, Inbred BALB C; Morphology; Necrosis; Neutrophils; Pharmacy; Respiratory system agents; Respiratory tract diseases; Signs and symptoms; Studies; Th1 Cells - drug effects; Th1 Cells - immunology; Th1 Cells - metabolism; Th2 Cells - drug effects; Th2 Cells - immunology; Th2 Cells - metabolism; Transcription factors; Tumor necrosis factor; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Tumors; γ-Interferon; South Korea
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0224517

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.