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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.

SUBMITTER: Jiao J

PROVIDER: S-EPMC6237163 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Ma Huang Tang ameliorates bronchial asthma symptoms through the TLR9 pathway.

Jiao Jiayuan J Wu Jiming J Wang Jiali J Guo Yaping Y Gao Le L Liang Honggang H Huang Jian J Wang Jinhui J

Pharmaceutical biology 20181201 1

<h4>Context</h4>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.<h4>Objective</h4>The study identifies the possible mechanisms of MHT on ovalbumin (OVA)-induced acute bronchial asthma in mice.<h4>Materials and methods</h4>First, an asthma-related protein-protein interaction (PPI) network was constructed. And then, the acute bronchial asthma mice models were est ...[more]

PMID: 30415587

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Project description:BackgroundInfluenza is a common viral infection worldwide. Maoto (ma-huang-tang) was developed in ancient China and is used to alleviate flu symptoms. Currently, no meta-analyses have evaluated the efficacy and safety of maoto for alleviating flu symptoms.MethodsIn the present study, we searched MEDLINE/PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, a Japanese database (Ichushi), two Chinese databases (China National Knowledge Infrastructure and VIP), and two Korean databases (Korean Medical database and Korean Association of Medical Journal Editors) for studies published in or before October 2017. Clinical studies that compared maoto plus neuraminidase inhibitors (NAIs) vs. NAIs alone, or maoto alone vs. NAIs alone, were included in the present analysis. The primary outcome measure (efficacy) was the length of time from the start of medication to resolution of influenza symptoms (fever, headache, malaise, myalgia, and chills) and virus isolation. The secondary outcome measures (safety) were as follows: (1) side effects and adverse reactions, such as nausea, abnormal behaviour, or discontinuation of symptomatic treatment; (2) morbidity (complications caused by influenza infection) or mortality; and (3) hospitalisation for any reason.ResultsTwelve relevant studies were identified, including two randomised controlled trials (RCTs, N = 60) and ten non-randomised studies (NRSs, N = 1110). We found that maoto plus NAIs was superior to NAIs alone in terms of the duration of fever in one RCT (P < 0.05, median difference = - 6 h) and four NRSs (P = 0.003, weighted mean difference = - 5.34 h). The duration of symptoms or virus isolation did not differ between maoto and NAIs. No severe side effects or adverse reactions were reported related to maoto or NAIs.ConclusionsAlthough we could not reach a definitive conclusion because of the small sample sizes and high risk of bias in the analysed studies, maoto may lower the duration of fever when it is used alone or in combination with NAIs and may be a well-tolerated treatment. More RCTs are needed to determine the efficacy and safety of maoto.

Project description:Although Ma Huang Tang (MHT) has long been considered as a classical formula for respiratory infections like influenza, bronchitis and asthma, its chemical ingredients that really exert the main efficacy are still obscure. In this study we aimed to screen its antiviral components and investigate the potential mechanisms. The MDCK cellular research results showed that, among nine predominant ingredients of MHT, L-methylephedrin (LMEP), L-ephedrine (LEP) and D-pseudo- ephedrine (DPEP) significantly inhibited the proliferation of influenza A virus in vitro, and the inhibitory effect at 24?h after the treatment was more obvious than that at 48?h. They also significantly inhibited the mRNA expression levels of related genes in the TLR3, TLR4 and TLR7 signaling pathways, which were accompanied with the down-regulation of TNF-? level and the up-regulation of IFN-? level in the cell supernatant. Therefore, three Ephedra alkaloids exert an antiviral effect in vitro which may be closely related to the inhibition of viral replication and the modulation of inflammatory response. Animal research further indicated, at the 3rd and 7th days after infection, LEP and DPEP significantly attenuated lung injury, decreased lung index, virus load in the lung and the level of IL-1? in serum, inhibited the mRNA expression levels of TNF-?, TLR3, TLR4, TLR7, MyD88, NF-?B p65 and RIG-1 as well as the protein expression levels of TLR4, TLR7, MyD88 and NF-?B p65 and markedly increased thymus index, the level of IL-10 in serum and the mRNA expression level of IFN-?. LEP and DPEP have certain protective effects on the influenza virus-infected mice, which may be associated with their abilities of effectively alleviating lung injury, improving the immunologic function of infected mice and adjusting the host's TLRs and RIG-1 pathways. The overall findings demonstrate that, as effective and inexpensive natural substances, Ephedra alkaloids and MHT may have potential utility in clinical management.

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Ma Huang Tang ameliorates bronchial asthma symptoms through the TLR9 pathway.

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Ma Huang Tang ameliorates bronchial asthma symptoms through the TLR9 pathway.

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