Effects of maoto (ma-huang-tang) on transcriptome signature in influenza virus infection
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PROVIDER: PRJNA664704 | ENA |
REPOSITORIES: ENA
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Project description:We evaluated the effects of maoto, a traditional kampo medicine, as a herbal multi-compound medicine on host transcriptome responses in a mouse model of influenza infection. On the fifth day of oral administration to mice intranasally infected with influenza virus (A/PR/8/34 (H1N1), maoto significantly improved survival rate, decreased viral titer, and ameliorated the infection-induced phenotype as compared with control mice. Analysis of the lung and plasma transcriptome profile showed that maoto significantly up-regulated the expression of macrophage- and T-cell-related genes. Collectively, these results suggest that maoto regulates the host’s inflammatory response.
2021-10-21 | GSE158270 | GEO
Project description:Maoto, a traditional kampo medicine, has been clinically prescribed for influenza infection and is reported to relieve symptoms and tissue damage. In this study, we evaluated the effects of maoto as an herbal multi-compound medicine on host responses in a mouse model of influenza infection. On the fifth day of oral administration to mice intranasally infected with influenza virus [A/PR/8/34 (H1N1)], maoto significantly improved survival rate, decreased viral titer, and ameliorated the infection-induced phenotype as compared with control mice. Analysis of the lung and plasma transcriptome and lipid mediator metabolite profile showed that maoto altered the profile of lipid mediators derived from ω-6 and ω-3 fatty acids to restore a normal state, and significantly up-regulated the expression of macrophage- and T-cell-related genes. Collectively, these results suggest that maoto regulates the host's inflammatory response by altering the lipid mediator profile and thereby ameliorating the symptoms of influenza.
| S-EPMC7896050 | biostudies-literature
Project description: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.
| S-EPMC6237163 | biostudies-literature
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.
| S-EPMC6747051 | biostudies-literature
Project description:Frequent and drastic ambient temperature variation may cause respiratory diseases such as common cold and pneumonia, the mechanism for which is not fully understood, however, due to lack of appropriate animal models. Ma-Huang-Tang (MHT) is widely used in China for treatment of respiratory diseases. The present study aimed to investigate the effect of MHT on temperature alternation induced rat lung injury and explore underlying mechanisms. Male Sprague-Dawley rats were exposed to a cold environment for 1 h and then shifted to a warm environment for 30 min. This cold and warm alteration cycled 4 times. Rats were administrated with MHT (1.87 g/kg) by gavage 6 h after cold-warm-cycles. Cold-warm-cycles induced pulmonary microcirculatory disorders, lung edema and injury, decrease in the expression of tight junction proteins, increase in VE-cadherin activation, increase in the expression and activation of Caveolin-1, Src and NF-κB, and NADPH oxidase subunits p47phox, p40phox and p67phox membrane translocation and inflammatory cytokines production. All alterations were significantly ameliorated by post-treatment with MHT. This study showed that rats subjected to cold-warm-cycles may be used as an animal model to investigate ambient temperature variation-induced lung injury, and suggested MHT as a potential strategy to combat lung injury induced by temperature variation.
| S-EPMC5428516 | biostudies-literature
Project description:Ma huang tang (MHT) is a traditional herbal medicine comprising six medicinal herbs and is used to treat influenza-like illness. However, the effects of MHT on inflammatory skin diseases have not been verified scientifically. We investigated determining the inhibitory effects of MHT against inflammation responses in skin using HaCaT human keratinocyte cells. We found that MHT suppressed production of thymus and activation-regulated chemokine (TARC/CCL17), macrophage-derived chemokine (MDC/CCL22), regulated on activation of normal T-cell expressed and secreted (RANTES/CCL5), and interleukin-8 (IL-8) in tumor necrosis factor-α (TNF-α) and interferon-γ- (IFN-γ-) stimulated HaCaT cells. Consistently, MHT suppressed the mRNA expression of TARC, MDC, RANTES, and IL-8 in TNF-α and IFN-γ-stimulated cells. Additionally, MHT inhibited TNF-α and IFN-γ-stimulated signal transducer and activator of transcription 1 (STAT1) phosphorylation in a dose-dependent manner and nuclear translocation in HaCaT cells. Our finding indicates that MHT inhibits production and expression of inflammatory chemokines in the stimulated keratinocytes by downregulating STAT1 phosphorylation, suggesting that MHT may be a possible therapeutic agent for inflammatory skin diseases.
| S-EPMC5101387 | biostudies-literature
Project description:Sulfobacillus thermotolerans strain:Zhiyong Huang | isolate:Zhiyong Huang Genome sequencing
| PRJNA901636 | ENA
Project description:IntroductionTraditional herbal medicine (THM) contains a vast number of natural compounds with varying degrees of pharmacological activity. To elucidate the mode of action, comprehensive metabolite profiling in the plasma before and after administration of THM is essential.ObjectiveThe aim of this study was to explore and identify/annotate converted metabolites after administration of THM in humans.MethodsWe performed untargeted metabolome analysis of human plasma collected before and after administration of maoto (ma-huang-tang), a traditional Japanese Kampo medicine. Maoto-derived metabolites were then selected and annotated following the DAC-Met strategy, which is an annotation method that uses mass differences of major metabolic reactions among the detected peaks and a differential network analysis.ResultsAbout 80% of maoto-derived components were found to be converted forms. Following DAC-Met, the structures of 15 previously unidentified metabolites were determined, and five of these were later confirmed with authentic standards. Using published literature, we also reconstructed the metabolic pathway of maoto components in humans. A kinetic time-course analysis revealed their diverse kinetic profiles.ConclusionThe results demonstrated that time-resolved comprehensive metabolite profiling in plasma using the DAC-Met strategy is highly useful for elucidating the complex nature of THM.
| S-EPMC7183508 | biostudies-literature
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.
| S-EPMC6421694 | biostudies-literature
Project description:Purpose of this experiment was to study the host-transcriptional response to MA-15, MA-15epsilon, and MA-15-gamma in both young and aged mice to further understand the differences between response within each age group, and the age-related differences in response to each virus.
2014-06-02 | GSE36969 | GEO