Quantitative proteomic profiling of targeted proteins associated with Loki Zupa Decoction Treatment in OVA-Induced asthmatic mice

Wuniqiemu, Tulake; Qin, Jingjing; Teng, Fangzhou; Mohammadtursun, Nabijan; Cui, Jie; Liu, Yi; Tang, Weifeng; Zhu, Xueyi; Abduwaki, Muhammadjan; Nurahmat, Mammat; Wei, Ying; Dong, Jing

doi:10.1016/j.jep.2020.113343

Cited by 12 publications

(9 citation statements)

References 25 publications

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“…In the acute asthma mouse model, our results suggested that LKZP may have an effect on anti-airway remodelling, which was consistent with previous research results of our team (Wuniqiemu et al. 2021 ).…”

Section: Discussionsupporting

confidence: 93%

“…In a chronic asthma mouse model, the targeted proteins treated with LKZP have been investigated using proteomics technology, which demonstrated that in addition to improving lung function and airway inflammation, LKZP also has a significant effect on improving collagen deposition and mucus secretion by regulating the RMB 10 and COL6A6 activated proteins (Wuniqiemu et al. 2021 ). More in-depth research to clarify the precise mechanism and targeted proteins in acute asthma is urgently needed.…”

Section: Discussionmentioning

confidence: 99%

“…Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis has identified rosmarinus acid as the main active ingredient of H. officinalis and luteolin, iris and apigenin as the main active ingredients of Orris root through LC-MS/MS analysis (Wuniqiemu et al. 2021 ). Both animal experiments and clinical studies have demonstrated that LKZP has significant effects on treating respiratory diseases.…”

Section: Introductionmentioning

confidence: 99%

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Louki Zupa decoction attenuates the airway inflammation in acute asthma mice induced by ovalbumin through IL-33/ST2-NF-κB/GSK3β/mTOR signalling pathway

Huang

Xie

et al. 2022

Pharmaceutical Biology

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Context Asthma is a common respiratory system disease. Louki Zupa decoction (LKZP), a traditional Chinese medicine, presents a promising efficacy against lung diseases. Objective To investigate the pathogenic mechanism of asthma and reveal the intervention mechanism of LKZP. Materials and methods Forty-eight female Balb/c mice were randomly divided into 6 groups: normal control group (NC), ovalbumin (OVA)/saline asthma model group, OVA/LL group, OVA/LM group, OVA/LH group and OVA/DEX group ( n = 8 per group). The asthmatic mice were modelled through intraperitoneal injecting and neutralizing OVA. LKZP decoction was administrated by gavage at the challenge stage for seven consecutive days (2.1, 4.2 and 8.4 g/kg/day). We investigated the change in lung function, airway inflammation, mucus secretion and TH-1/TH-2-related cytokines. We further verify the activated status of the IL-33/ST2/NF-κB/GSK3β/mTOR signalling pathway. Results LKZP was proved to improve asthmatic symptoms, as evidenced by the down-regulated airway resistance by 36%, 58% and 53% ( p < 0.01, p < 0.001 vs. OVA/saline group), up-regulated lung compliance by 102%, 114% and 111%, decreased airway inflammation and mucus secretion by 33%, 40% and 33% ( p < 0.001 vs. OVA/saline group). Moreover, the content of cytokines in BALF related to airway allergy (such as IgE) and T helper 1/T helper 2 cells (like IL-2, IL-4, IL-5, IL-13, TNF-α and IFN-γ), were also markedly reduced by 13–65% on LKZP intervention groups compared with model group. Mechanistic research revealed that the IL-33/ST2-NF-κB/GSK3β/mTOR signalling pathway was activated in the OVA/saline group and LKZP significantly down-regulated this pathway. Discussion and conclusion LKZP improves lung function, airway inflammation, mucus secretion and correct immune imbalance by intervening with the IL-33/ST2-NF-κB/GSK3β/mTOR signalling pathway, presenting a promising therapeutic choice for asthma.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Louki Zupa decoction attenuates the airway inflammation in acute asthma mice induced by ovalbumin through IL-33/ST2-NF-κB/GSK3β/mTOR signalling pathway

Huang

Xie

et al. 2022

Pharmaceutical Biology

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“…HE, PAS, and MT staining respectively displayed massive infiltration of inflammatory cells, mucus hypersecretion, and airway structure change in lung tissues. Overall, these results validated that OVA successfully induced airway hyperresponsiveness and inflammation, goblet cell hyperplasia, and airway remodeling, which conform to the pathological changes of asthma ( 44 , 45 ), thus demonstrating the effectiveness of our model.…”

Section: Discussionsupporting

confidence: 73%

“…One day after the last OVA challenge (day 21), airway resistance and dynamic compliance ( C dyn ) in mice were evaluated using the FinePointe RC System (DSI Buxco Electronics, Troy, NY, USA). Specific details of the measurement were described in our previous study ( 44 , 45 ). Briefly, mice were intubated by tracheotomy under anesthesia and ventilated with 2 μl nebulized methacholine of different concentrations (0, 3.125, 12.5, and 50 mg/ml).…”

Section: Methodsmentioning

confidence: 99%

N6-Methyladenosine Methylomic Landscape of Lung Tissues in Murine Acute Allergic Asthma

et al. 2021

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Allergic asthma is well known as a common respiratory disorder comprising an allergic inflammatory nature and excessive immune characteristic. N6-methyladenosine (m6A) methylation is an RNA epigenetic modification that post-transcriptionally regulates gene expression and function by affecting the RNA fate. Currently, m6A methylation is gaining attention as a mechanism of immunoregulation. However, whether m6A methylation engages the pathological process of asthma remains uncertain. Here, we present the m6A methylomic landscape in the lung tissues of ovalbumin-induced acute asthma mice using MeRIP-seq and RNA-seq. We identified 353 hypermethylated m6A peaks within 329 messenger RNAs (mRNAs) and 150 hypomethylated m6A peaks within 143 mRNAs in the lung tissues of asthmatic mice. These differentially methylated mRNAs were found to be involved in several immune function-relevant signaling pathways. In addition, we predicted 25 RNA-binding proteins that recognize the differentially methylated peak sites by exploring public databases, and the roles of these proteins are mostly related to mRNA biogenesis and metabolism. To further investigate the expression levels of the differentially methylated genes, we performed combined analysis of the m6A methylome and transcriptome data and identified 127 hypermethylated mRNAs (107 high and 20 low expression) and 43 hypomethylated mRNAs with differential expressions (9 high and 34 low expression). Of these, there are a list of mRNAs involved in immune function and regulation. The present results highlight the essential role of m6A methylation in the pathogenesis of asthma.

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Transcriptomics reveals apigenin alleviates airway inflammation and epithelial cell apoptosis in allergic asthma via MAPK pathway

Huang

Xie

et al. 2023

Phytotherapy Research

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Persistent chronic inflammation of the lungs and airway remodeling are important pathological features that cannot be ignored in patients with chronic asthma. Apigenin (API) is a natural small molecule compound with good anti‐inflammatory and antioxidant activity that has been widely reported in recent years, but its role in chronic asthma is not well defined. Our study began with oral gavage intervention using API (10, 20 mg/kg) or dexamethasone (DEX, 2 mg/kg) in a BALB/c mouse model of ovalbumin (OVA) sensitization. Different doses of API intervention effectively reduced airway resistance in the administered group. Additionally, inflammation was downregulated, mucus secretion was reduced, and airway remodeling was inhibited in the API intervention group compared with the model group. Asthma‐related inflammatory cytokines, such as IgE, IL‐4, IL‐5, IL‐13, and IL‐17, were downregulated in alveolar lavage fluid. Moreover, the apoptosis level of the administered group was found to be lower than that of the model group in the Tunel staining experiment. By analyzing transcriptome sequencing results, we found that API may exert anti‐inflammatory and anti‐apoptotic effects by inhibiting the MAPK pathway. Our subsequent results supported this conclusion, showing that the phosphorylation levels of ERKs, JNKs, and p38 MAPKs were inhibited in the administered group relative to the model group. Downstream expression of the apoptosis‐related protein B‐cell lymphoma‐2 (Bcl‐2) was upregulated, and the expression of Bcl‐2‐associated × protein (Bax) and cleaved caspase‐3 was downregulated. To further investigate the specific mechanism by which API acted, we established an in vitro model with house dust mite (HDM) stimulation, using API (10, 20 μM) for administration intervention. The results showed that API was able to improve cell viability, inhibit ROS production, and reverse HDM‐induced decreases in mitochondrial membrane potential (MMP) and apoptosis in airway epithelial cells via the MAPK pathway.

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Quantitative proteomic profiling of targeted proteins associated with Loki Zupa Decoction Treatment in OVA-Induced asthmatic mice

Cited by 12 publications

References 25 publications

Louki Zupa decoction attenuates the airway inflammation in acute asthma mice induced by ovalbumin through IL-33/ST2-NF-κB/GSK3β/mTOR signalling pathway

Louki Zupa decoction attenuates the airway inflammation in acute asthma mice induced by ovalbumin through IL-33/ST2-NF-κB/GSK3β/mTOR signalling pathway

N6-Methyladenosine Methylomic Landscape of Lung Tissues in Murine Acute Allergic Asthma

Transcriptomics reveals apigenin alleviates airway inflammation and epithelial cell apoptosis in allergic asthma via MAPK pathway

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