Ma Huang Tang ameliorates bronchial asthma symptoms through the TLR9 pathway

Abstract

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.

Регуляторные Механизмы Системного Воспаления При Респираторной Патологии

“…В первую очередь активируется TLR4, позднее подключается TLR3 [459]. В ABCA1-макрофагах (ATP binding cassette protein A1 (ABCA1)) в ответ на действие LPS и специфических агонистов TLR2, TLR7 и TLR9 развивается провоспалительная реакция [305]. Липидные рафты ABCA1-дефицитных макрофагов характеризуются повышенным уровнем холестерина и активностью TLR4 и TLR9 после воздействия на клетки лигандов этих рецепторов.…”

“…Примечательно, что отложение холестерина может также вызывать провоспалительные реакции в клетках с помощью TLRнезависимых механизмов. Макрофаги, имеющие повышенный уровень холестерина в мембране, секретируют TNFα и IL-6 через ______________________________________________________Глава 2 активацию стресс-индуцируемого белка CHOP (C/EBP homologous protein (CHOP)), участвующего в регуляции транскрипции, клеточного цикла и апоптоза [305].…”

Unraveling the Molecular Mechanism of Traditional Chinese Medicine: Formulas Against Acute Airway Viral Infections as Examples

“…MHT clearly shows anti-inflammatory activity via suppressing the NO/PGE2 pathway [77], reducing inflammatory cells infiltration and reducing pro-inflammatory cytokine, including TNF-α, IL-1β, and IL-6, in lung experiments [78]. In an acute bronchial asthma mice model, MHT can also mitigate the pathological changes of acute asthma-like syndrome through inhibition of the Toll-like receptor 9 (TLR9) pathway [79]. MHT can modulate Th1/Th2 cytokines via decreasing IL-4 & IL-17 and increasing IFN-γ levels.…”

Ding Chuan Tang Attenuates Airway Inflammation and Eosinophil Infiltration in Ovalbumin-Sensitized Asthmatic Mice

“…Herbal medicines can also be conducted into decoctions for therapeutic approach. For asthma, Xiao-Qing-Long-Tang [ 19 ] and Ma Huang Tang [ 20 ] have been reported to reduce airway hyperresponsiveness (AHR), IgE production, or eosinophil infiltration in allergen-induced asthmatic models. Also, Pingchuan formula has been reported to restore Treg/Th17 balance and downregulate the TLR2-ERK signaling pathway to reduce asthmatic symptoms [ 21 , 22 ].…”