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

Int Immunopharmacol. 2020 Jun:83:106423. doi: 10.1016/j.intimp.2020.106423. Epub 2020 Apr 9.

Abstract

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.

Keywords: Asthma; Ephedra; Inflammation; Mechanism; Network pharmacology.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Asthma / drug therapy*
  • Asthma / metabolism*
  • Chemokine CXCL10 / metabolism
  • Databases, Genetic
  • Databases, Pharmaceutical
  • Drugs, Chinese Herbal / chemistry*
  • Drugs, Chinese Herbal / therapeutic use
  • E-Selectin / metabolism
  • Ephedra / chemistry*
  • Ephedra / metabolism*
  • Humans
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Interleukin-2 / metabolism
  • Mice
  • Molecular Docking Simulation / methods
  • Protein Binding
  • Protein Interaction Mapping / methods
  • Protein Interaction Maps
  • RAW 264.7 Cells
  • Systems Biology / methods

Substances

  • Anti-Inflammatory Agents
  • Chemokine CXCL10
  • Drugs, Chinese Herbal
  • E-Selectin
  • Interleukin-2
  • SELE protein, human