Inula helenium and Grindelia squarrosa as a source of compounds with anti-inflammatory activity in human neutrophils and cultured human respiratory epithelium

J Ethnopharmacol. 2020 Mar 1:249:112311. doi: 10.1016/j.jep.2019.112311. Epub 2019 Oct 20.

Abstract

Ethnopharmacological relevance: During the epidemic season, over 90% of acute wheezing disease is associated with bronchial inflammation. Both neutrophil- and eosinophil-mediated inflammation have been involved in the pathophysiology of acute bronchitis, but neutrophil cell recruitment has been shown to be dominant. The ongoing inflammation increases the chemotaxis of neutrophils to inflamed site providing to their overaccumulation. The pharmacological reduction of neutrophil migration can be limited by suppression of major chemo-attractants and cytokines (IL-8, IL-1β and TNF-α) release and downregulation of adhesive molecules.

Aim of the study: During a screening of plants traditionally used in respiratory tracts diseases (e.g. cough, rhinitis, bronchitis, throat infection, fever, influenza) in Europe, we have selected roots of Inula helenium and aerial parts of Grindelia squarrosa as a potential source of compounds limiting neutrophil migration.

Materials and methods: The effect on IL-8, IL-1β and TNF-α release by neutrophils and respiratory epithelium cell line (A549) was measured by enzyme-linked immunosorbent assay (ELISA). The surface expression of adhesive molecules was analyzed with flow cytometry, and the neutrophil attachment to the epithelial cells was assessed fluorimetrically.

Results: We confirmed the ability of selected extracts and compounds to suppress neutrophil binding to the epithelium surface via downregulation of β2 integrin. Alantolactone and grindelic acid have shown significant suppression of IL-8, TNF-α and IL-1β release comparable with budesonide, used as a positive control.

Conclusions: The present study demonstrated that Inula helenium and Grindelia squarrosa, which have been traditionally used in Europe as medicinal plants, are a valuable source of active compounds with anti-inflammatory activity. Our observations justify the traditional use of I. helenium and G. squarrosa for a treatment of inflammation-based diseases in respiratory tract.

Keywords: Grindelia squarrosa; Human respiratory epithelium; Interleukin 8; Inula helenium; Neutrophils; Pro-inflammatory mediators.

MeSH terms

  • A549 Cells
  • Adolescent
  • Adult
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • Cell Line, Tumor
  • Cytokines / metabolism
  • Diterpenes / pharmacology
  • Down-Regulation / drug effects
  • Europe
  • Grindelia / chemistry*
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Interleukin-1beta / metabolism
  • Interleukin-8 / metabolism
  • Inula / chemistry*
  • Lactones / pharmacology
  • Neutrophils / drug effects*
  • Neutrophils / metabolism
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology
  • Plants, Medicinal / chemistry
  • Respiratory Mucosa / drug effects*
  • Respiratory Mucosa / metabolism
  • Sesquiterpenes, Eudesmane / pharmacology
  • Tumor Necrosis Factor-alpha / metabolism
  • Young Adult

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Diterpenes
  • Interleukin-1beta
  • Interleukin-8
  • Lactones
  • Plant Extracts
  • Sesquiterpenes, Eudesmane
  • Tumor Necrosis Factor-alpha
  • grindelic acid
  • alantolactone