Artesunate inhibits airway remodeling in asthma via the MAPK signaling pathway

Zhang, Mengyuan; Lin, Jiangtao; Zhang, Jingyuan; Zhao, Ruiheng; Wan, Jinghai; Nong, Ying

doi:10.3389/fphar.2023.1145188

Cited by 5 publications

(5 citation statements)

References 75 publications

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“…HE staining was used to evaluate the airway inflammation. The inflammation surrounding the bronchus and blood vessels was observed using an optical microscope in each section, with the inflammation score ranging from 0 to 5 points ( Zhang et al, 2023 ). PAS staining was used to assess airway mucus secretion, while masson’s trichrome staining evaluated collagen deposition.…”

Section: Methodsmentioning

confidence: 99%

Mechanisms of Bushenyiqi decoction in the treatment of asthma: an investigation based on network pharmacology with experimental validation

Qin,

Chen,

Liu

et al. 2024

Front. Pharmacol.

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Background and purpose: The Bushenyiqi decoction (BYD), a contemporary prescription of traditional Chinese medicine (TCM), has been observed to significantly ameliorate asthma symptoms in patients based on clinical observations. Although multi-component and multi-target characteristics are important attributes of BYD treatment, its pharmacological effect on asthma and the underlying mechanism of action remain unclear.Method: Network pharmacology: the asthma-related genes were retrieved from the GeneCards and OMIM database. The active constituents of BYD and their corresponding target genes were collected from the TCMSP database. The underlying pathways associated with overlapping targets between BYD and asthma were identified through GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis. Experimental validation: pulmonary function tests, enzyme-linked immunosorbent assay (ELISA), Hematoxylin and eosin (HE), periodic acid-Schiff (PAS), and Masson’s trichrome stainings were conducted to validate the efficacy of BYD in ameliorating airway inflammation in allergic asthma mice. Western blot (WB) and molecular docking were performed to confirm the involvement of the underlying pathway in BYD treatment of asthma.Results: The results of animal experiments demonstrated that BYD may improve airway responsiveness and suppress airway inflammation in allergic asthma mice. The network pharmacological analysis revealed the involvement of 11 potentially key active components, 9 potential key targets, and the phosphatidylinositol3 kinase-RAC-α serine/threonine-protein kinase (PI3K/AKT) signaling pathway in the mechanism of action of BYD for asthma treatment. Our findings have confirmed that BYD effectively alleviated airway inflammation by targeting interleukin 6 (IL-6), epidermal growth factor receptor (EGFR), and hypoxia inducible factor 1 alpha (HIF1A), with quercetin, kaempferol, and luteolin performing as the pivotal active constituents. BYD may potentially reduce inflammatory cell infiltration in lung tissues by regulating the PI3K/AKT signaling pathway.Conclusion: In conclusion, the integration of network pharmacology and biological experiments has demonstrated that key constituents of BYD, such as quercetin, kaempferol, and luteolin, exhibit targeted effects on IL-6, EGFR, and HIF1A in combating asthma-related inflammation through inhibition of the PI3K/AKT signaling pathway. The findings of this investigation provide evidence supporting the effectiveness of TCM’s “bushenyiqi” therapy in asthma management, as corroborated by contemporary medical technology.

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Section: Methodsmentioning

confidence: 99%

Mechanisms of Bushenyiqi decoction in the treatment of asthma: an investigation based on network pharmacology with experimental validation

Qin,

Chen,

Liu

et al. 2024

Front. Pharmacol.

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“…(4) Patients who are allergic to the active ingredient of the vaccine or to any dressing. (5) Patients who are combined with other respiratory diseases, such as allergic bronchopulmonary aspergillosis, hypersensitivity pneumonia, pulmonary malignancy, pulmonary, bronchiectasis, tuberculosis, idiopathic pulmonary interstitial fbrosis, and pulmonary sarcoidosis. In addition, inhalation technique and compliance were checked.…”

Section: Study Populationmentioning

confidence: 99%

“…Studies showed that omalizumab responders had signifcantly younger age in the adult subgroup, higher pretreatment total serum IgE level, percent predicted FEV1, and fractional exhaled nitric oxide (FeNO) than nonresponders [4]. Other studies indicated responsiveness of omalizumab is not associated with pretreatment clinical biomarkers, including FeNO, serum total IgE, FEV1, and blood eosinophils [5]. So far there is no consensus opinion.…”

Section: Introductionmentioning

confidence: 99%

Clinical Response Predictive Model for Omalizumab in Moderate-to-Severe Asthma Patients

Qian,

Yang,

Shen

et al. 2024

International Journal of Clinical Practice

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Objective. Our study aimed to develop a predictive model for evaluating the clinical response of omalizumab treatment in moderate-to-severe asthma patients. Methods. This single-center, prospective study collected patients who meet the diagnostic criteria for moderate-to-severe bronchial asthma set by the National Asthma Prevention and Treatment Group in 2016 in the first hospital affiliated with Soochow University. Patients recruited were treated with omalizumab once per four weeks; at the beginning of each injection, blood eosinophils and the level of total serum IgE (IU/mL) were tested. After four injections of omalizumab, asthma control test (ACT), the 15-item Mini Asthma Quality of Life Questionnaire (MiniAQLQ), global treatment effectiveness (GETE), and lung function of all patients were evaluated in the 16th week. We used the selection operator method to build a logistic model and evaluated the clinical response of omalizumab in these patients. Results. This study included 108 moderate-to-severe patients (aged 39.86 ± 14.59 years). Eighty-nine patients finished treatment for 16 weeks, and 74 patients (83.1%) had an excellent or good response. The serum level of total IgE increased significantly after injection of omalizumab, while blood eosinophils count decreased significantly from baseline. Using the GETE as a clinical outcome, several clinical variables were significant predictors of clinical response. The corrected AUC and Brier scores were 0.872 and 0.111, which showed good discrimination. Significant variables included age, weight, family allergic history, acute exacerbations, the ratio of total serum IgE level at the 4th week to the baseline level, forced expiratory volume in one second/forced vital capacity (FEV1/FVC), and commodities of rhinitis. Using the improvement in maximal expiratory flow 25% of the measured value to the predicted value (MEF25%pre) as clinical outcome, the significant variables included weight, duration of asthma, use of oral corticosteroids (OCS), total serum IgE level at the 4th week, and history of rhinitis. Its corrected AUC and Brier scores were 0.674 and 0.225 after internal validation. Conclusion. Omalizumab treatment remarkably improved asthma control and pulmonary function in Chinese patients with moderate-to-severe asthma. The response prediction model we developed provides convenient approaches to help identify better clinical response patients to omalizumab treatment.

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“…Galangin [64] OVA-induced asthma in mice TGF-β1, MMP9, VEGF Artesunate [65] OVA-induced asthma in mice MAPK Ginkgolic acid [66] Pulmonary fbrosis in mice Smad4 caused by oxidative stress [75,76]. Moreover, naringenin was shown to have a signifcant therapeutic on Mycoplasma pneumoniae-induced lung injury in mice by inhibiting pulmonary fbrosis and inhibiting the secretion of infammatory cytokines such as IL-6, IL-1β, TNF-α, and TGF-β [60].…”

Section: Te Efect Of Specifc Herbal Compounds On Emtmentioning

confidence: 99%

“…Artesunate is a semisynthetic single compound isolated from the plant Artemisia annua. Artesunate may decrease infammation and attenuate airway remodeling in asthmatic mice via the MAPK signalling pathway [65].…”

Section: Te Efect Of Specifc Herbal Compounds On Emtmentioning

confidence: 99%

Medicine Targeting Epithelial-Mesenchymal Transition to Treat Airway Remodeling and Pulmonary Fibrosis Progression

He,

Ji,

Cao

et al. 2023

Canadian Respiratory Journal

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Objective. Dysregulation of epithelial-mesenchymal transition (EMT) in the airway epithelium is associated with airway remodeling and the progression of pulmonary fibrosis. Many treatments have been shown to inhibit airway remodeling and pulmonary fibrosis progression in asthma and chronic obstructive pulmonary disease (COPD) by regulating EMT and have few side effects. This review aimed to describe the development of airway remodeling through the EMT pathway, as well as the potential therapeutic targets in these pathways. Furthermore, this study aimed to review the current research on drugs to treat airway remodeling and their effects on the EMT pathway. Findings. The dysregulation of EMT was associated with airway remodeling in various respiratory diseases. The cytokines released during inflammation may induce EMT and subsequent airway remodeling. Various drugs, including herbal formulations, specific herbal compounds, cytokines, amino acid or protein inhibitors, microRNAs, and vitamins, may suppress airway remodeling by inhibiting EMT-related pathways.

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Artesunate inhibits airway remodeling in asthma via the MAPK signaling pathway

Cited by 5 publications

References 75 publications

Mechanisms of Bushenyiqi decoction in the treatment of asthma: an investigation based on network pharmacology with experimental validation

Mechanisms of Bushenyiqi decoction in the treatment of asthma: an investigation based on network pharmacology with experimental validation

Clinical Response Predictive Model for Omalizumab in Moderate-to-Severe Asthma Patients

Medicine Targeting Epithelial-Mesenchymal Transition to Treat Airway Remodeling and Pulmonary Fibrosis Progression

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