The association of <i>NLRP3</i> and <i>TNFRSF1A</i> polymorphisms with risk of ankylosing spondylitis and treatment efficacy of etanercept

Wang

2020

Preprint

Background: Network pharmacological methods were used to predict the anti-inflammatory targets and related pathways of rhein in the treatment of asthma, and to elucidate its mechanism of action. In addition, we validated the anti-inflammatory effects of rhein in HBE cells. Methods: The corresponding targets of rhein were obtained from the TCMSP 2.3, and molecular docking was also performed. A network of predicted rhein targets was established and analysed with Cytoscape 3.7.1. The anti-inflammatory targets in the TTD database were searched to build a PPI network, which was merged with the ingredient-target network to screen anti-inflammatory targets associated with rhein. A network of anti-inflammatory rhein targets during the in vivo treatment of asthma was constructed to screen the anti-inflammatory targets related to asthma. KEGG enrichment analysis was performed with the Enrichr database and Cytoscape 3.7.1. The expression levels of proteins in the MAPK/NF-κB signalling pathway were assessed by western blot analysis. Results: Altogether, 17 targets were obtained. Epidermal active growth factor receptor (EGFR), E-selecting (E-SELE), macrophage migration inhibitory factor (MIF), and mitogen-activated protein kinase 14 (MAPK14) might be important anti-inflammatory targets of rhein during asthma treatment. We selected the MAPK signalling pathway to determine the anti-inflammatory effects of rhein. Conclusion: The anti-inflammatory mechanism of the treatment of asthma with rhein may be related to MAPK14, EGFR, E-SELE and MIF as well as their signalling pathways. To prevent the exacerbation of asthma, instead of targeting a single pathway or a single target, all these targets and their signalling pathways should be controlled holistically. Rhein may reduce inflammation by inhibiting the MAPK/NF-κB pathway.

Section: Discussionmentioning

confidence: 99%

Anti-inflammatory Mechanism of Rhein in Treating Asthma Based on Network Pharmacology

Wang

2020

Preprint

“…TNFRSF1A is a type 1 TNF receptor that mediates inflammatory responses mainly by activating NF-κB, p38, ERK1/2 to induce IL-6, IL-8 synthesis and apoptosis [24,25]. It is thus concluded that Rhein interacts with TNFRSF1A to reduce the release of anti-inflammatory factors such as IL-6 and exert an anti-inflammatory effect.…”

Section: Discussionmentioning

confidence: 99%

Anti-inflammatory Mechanism of Rhein in Treating Asthma Based on Network Pharmacology

Wang

2020

Preprint

BackgroundNetwork pharmacology was used to study Rhein -target-pathway and to clarify its anti-inflammatory mechanism in the treatment of asthma.and provide a new idea for the treatment of asthmaMethodsThis method, which allows using network pharmacology to figure out the operational mechanism of Rhein-Target-Pathway, defines the effect of anti-inflammatory in treating asthma. The platform of Traditional Chinese Medicine Molecular Mechanism Bioinformatics, a web server for network, is used to get the corresponding target of Rhein and permit molecular docking. Cytoscape3.7.1, a kind of network software, is used to construct Rhein-predicted target network and analyse network topology. Search anti-inflammatory targets in the database of TTD and then construct the PPI network as well as create protein interaction networks that are combined with the Rhein-predicted target network. The anti-inflammatory targets of Rhein should be presented. The asthma genes of human being can be attained from the database of NCBI Gene Database and construct correspondence vivo response network model. Find Anti-inflammatory targets of Rhein against asthma, screen anti-inflammatory targets of Rhein related with Pathogenesis of asthma. Enrichr database is used to analyse signal pathway from anti-inflammatory targets of Rhein KEGG.ResultsAccording to the study, Rhein corresponds to 17 target proteins, four anti-inflammatory targets of Rhein related to asthma(MAPK14, EGFR, ERBB2, TNFRSF1A) are probably the most important targets where asthma is treated by Rhein.ConclusionsThese four anti-inflammatory targets of Rhein related to asthma are probably the key targets in the treatment of asthma by using Rhein. For the purpose of preventing the occurrence as well as development of asthma and delaying the progress of the disease, one or some of the four anti-inflammatory targets of Rhein related to asthma can be controlled.

“…TNFRSF1A is a type 1 TNF receptor that mediates in ammatory responses mainly by activating NF-κB, p38, and ERK1/2 to induce IL-6 and IL-8 synthesis and apoptosis [33,34]. It is thus concluded that rhein interacts with TNFRSF1A to reduce the secretion of anti-in ammatory factors, such as IL-6, and exert an anti-in ammatory effect.…”

Section: Discussionmentioning

confidence: 99%

Anti-inflammatory Mechanism of Rhein in Treating Asthma Based on Network Pharmacology

Wang³

2020

Preprint

Background: Network pharmacological methods were used to predict the anti-inflammatory targets and related pathways of rhein in the treatment of asthma, and to elucidate its mechanism of action. In addition, we validated the anti-inflammatory effects of rhein in human bronchial epithelial (HBE) cells.Methods: The corresponding targets of rhein were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform 2.3 (TCMSP), and molecular docking was also performed. A network of predicted rhein targets was established and analysed with Cytoscape 3.7.1. The anti-inflammatory targets in the Therapeutic Target Database 2020 (TTD) were searched to build a protein-protein interaction network (PPI), which was merged with the ingredient-target network to screen anti-inflammatory targets associated with rhein. A network of anti-inflammatory rhein targets during the in vivo treatment of asthma was constructed to screen the anti-inflammatory targets related to asthma. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed with the Enrichr database and Cytoscape 3.7.1. The expression levels of proteins in the mitogen-activated protein kinase / nuclear factor kappa-B (MAPK/NF-κB) signalling pathway were assessed by western blot analysis.Results: Altogether, Eighty-three targets were obtained. Epidermal active growth factor receptor (EGFR), E-selecting (E-SELE), macrophage migration inhibitory factor (MIF), and mitogen-activated protein kinase 14 (MAPK14) might be important anti-inflammatory targets of rhein during asthma treatment. We selected the MAPK signalling pathway to determine the anti-inflammatory effects of rhein.Conclusion: The anti-inflammatory mechanism of the treatment of asthma with rhein may be related to MAPK14, EGFR, E-SELE and MIF as well as their signalling pathways. To prevent the exacerbation of asthma, instead of targeting a single pathway or a single target, all these targets and their signalling pathways should be controlled holistically. Rhein may reduce inflammation by inhibiting the MAPK/NF-κB pathway.