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

Abstract

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 vitro.Methods: The corresponding targets of rhein were obtained from the TCMSP database, and molecular docking was 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-selectin (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, 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.