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Ma Huang Tang ameliorates bronchial asthma symptoms through the TLR9 pathway

Jiao, Jiayuan, Wu, Jiming, Wang, Jiali, Guo, Yaping, Gao, Le, Liang, Honggang, Huang, Jian, Wang, Jinhui
Pharmaceutical biology 2018 v.56 no.1 pp. 580-593
Ephedra sinica, Toll-like receptor 9, animal models, asthma, breathing, computer simulation, drug therapy, eosinophils, fever, genes, immunohistochemistry, inflammation, influenza, lethal dose 50, lungs, mice, ovalbumin, patients, protein-protein interactions, sequence analysis, signal transduction, staining, tissues
Context: Ma Huang Tang (MHT) has been used to treat influenza, fever, bronchial asthma, etc. as a traditional Chinese medication. However, the anti-inflammation mechanism of MHT remains unclear. Objective: The study identifies the possible mechanisms of MHT on ovalbumin (OVA)-induced acute bronchial asthma in mice. Materials and methods: First, an asthma-related protein-protein interaction (PPI) network was constructed. And then, the acute bronchial asthma mice models were established by exposing to aerosolized 1% ovalbumin for 30 min/day for 1 week, and the mice were administered 2.0, 4.0, or 8.0 g/kg of MHT daily. To evaluate therapeutic effect, sensitization time, abdominal breathing time, eosinophils in bronchoalveolar lavage fluid, and tissue and trachea pathology were examined. Related genes were measured using RNA sequencing (RNA-seq). The expression levels of TLR9 in lung and trachea tissues were determined by immunohistochemical staining. Results: MHT had a LD₅₀ = 19.2 g/kg against asthma, while MHT at high doses (8 g/kg) effectively extended the sensitization time and abdominal breathing time and alleviated OVA-induced eosinophilic airway inflammation and mitigated pathological changes. The RNA-seq assay showed that the high-dose MHT resulted in a significant decrease in the levels of TLR9, TRAF6, TAB2, etc. in the lung tissue. Immunohistochemical assay confirmed the down-regulated of TLR9. Molecular docking revealed that six MHT compounds potentially mediated the TLR9 signaling pathway. Discussion and conclusions: MHT could mitigate the pathological changes of acute asthma-like syndrome through inhibition of the TLR9 pathway. Results of this study may provide a reference for the development of a novel therapy for patients with allergic asthma.