A network pharmacology-based strategy for predicting anti-inflammatory targets of ephedra in treating asthma

• Published in: International immunopharmacology Vol. 83; p. 106423
• Main Authors: Huang, Xiu-Fang, Cheng, Wen-Bin, Jiang, Yong, Liu, Qiong, Liu, Xiao-Hong, Xu, Wei-Fang, Huang, Hui-Ting
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2020; Elsevier BV
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Asthma; Asthma - drug therapy; Asthma - metabolism; Biological activity; Chemokine CXCL10 - metabolism; CXCL10 protein; Databases, Genetic; Databases, Pharmaceutical; Drugs, Chinese Herbal - chemistry; Drugs, Chinese Herbal - therapeutic use; E-Selectin - metabolism; Ephedra; Ephedra - chemistry; Ephedra - metabolism; Humans; Immune response; Immune system; Inflammation; Inflammation - drug therapy; Inflammation - metabolism; Inflammatory response; Interleukin 2; Interleukin-2 - metabolism; Lipopolysaccharides; Mechanism; Mice; Molecular docking; Molecular Docking Simulation - methods; mRNA; Naringenin; Network pharmacology; Pharmacology; Protein Binding; Protein interaction; Protein Interaction Mapping - methods; Protein Interaction Maps; Proteins; Quercetin; RAW 264.7 Cells; Respiratory diseases; Systems Biology - methods; Network pharmacology; Inflammation; Ephedra; Mechanism; Asthma
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2020.106423

•5 key compounds were obtained including quercetin, kempferol, naringenin, beta-sitostero and luteolin.•SELE, IL-2 and CXCL10 were firstly selected as critical targets for ephedra against inflammation in asthma.•Quercetin, kempferol, naringenin, beta-sitostero and luteolin had good binding activities to SELE, IL-2 and CXCL10.•Quercetin and luteolin were proved to decreased the expression of SELE, IL-2 and CXCL10 at protein and mRNA levels.•This study provides new perspective to deepen the understanding of the physical basis and pharmacology of ephedra against inflammation in asthma. Asthma, the most common chronic respiratory disease in the world, is involved in a sustained inflammatory response caused by a variety of immune cells. Ephedra with multi-target, multi-pathway functions is an effective treatment for asthma. However, the ingredients and anti-inflammatory targets of ephedra in treating asthma are unclear. Therefore, there is a need for further research. Ephedra-related and anti-inflammatory targets were found and then combined to get intersection, which represented potential anti-inflammatory targets of ephedra. Moreover, compound-anti-inflammatory target and asthma-target protein-protein interaction network were merged to get the protein-protein interaction network intersection and core genes in asthma-target protein-protein interaction network. For the anti-inflammatory targets of ephedra in treating asthma, Gene Ontology and pathway analysis were executed to confirm gene functions of ephedra in antagonizing inflammation of asthma. Finally, molecular docking, qRT-PCR, WB and ELISA were performed to assess the binding activities between the compounds and anti-inflammatory targets of ephedra in treating asthma. Critical compounds and anti-inflammatory targets of ephedra in treating asthma were identified, including quercetin, luteolin, kempferol, naringenin, beta-sitosterol, SELE, IL-2 and CXCL10. The biological processes of anti-inflammatory targets of ephedra in treating asthma were involved in immune response, inflammatory response, cell-cell signaling and response to lipopolysaccharide. Moreover, 22 pathways were obtained and we proved that critical compounds inhabited the expression of SELE, IL-2 and CXCL10 at mRNA and protein levels.