Anti-inflammatory effects of the petasin phyto drug Ze339 are mediated by inhibition of the STAT pathway

Biofactors. 2017 May 6;43(3):388-399. doi: 10.1002/biof.1349. Epub 2017 Jan 31.

Abstract

Ze339, an herbal extract from Petasites hybridus leaves is effective in treatment of allergic rhinitis by inhibition of a local production of IL-8 and eicosanoid LTB4 in allergen-challenged patients. However, the mechanism of action and anti-inflammatory potential in virally induced exacerbation of the upper airways is unknown. This study investigates the anti-inflammatory mechanisms of Ze339 on primary human nasal epithelial cells (HNECs) upon viral, bacterial and pro-inflammatory triggers. To investigate the influence of viral and bacterial infections on the airways, HNECs were stimulated with viral mimics, bacterial toll-like-receptor (TLR)-ligands or cytokines, in presence or absence of Ze339. The study uncovers Ze339 modulated changes in pro-inflammatory mediators and decreased neutrophil chemotaxis as well as a reduction of the nuclear translocation and phosphorylation of STAT molecules. Taken together, this study suggests that phyto drug Ze339 specifically targets STAT-signalling pathways in HNECs and has high potential as a broad anti-inflammatory drug that exceeds current indication. © 2016 BioFactors, 43(3):388-399, 2017.

Keywords: STAT signalling; cytokines; human nasal epithelial cells; microbial patterns; petasin; viral inflammation.

MeSH terms

  • Cell Movement / drug effects
  • Chemokines / antagonists & inhibitors
  • Chemokines / biosynthesis
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Flagellin / antagonists & inhibitors
  • Flagellin / pharmacology
  • Gene Expression Regulation
  • Humans
  • Interferon-gamma / antagonists & inhibitors
  • Interferon-gamma / pharmacology
  • Interleukin-4 / antagonists & inhibitors
  • Interleukin-4 / pharmacology
  • Lipopeptides / antagonists & inhibitors
  • Lipopeptides / pharmacology
  • Nasal Cavity / cytology
  • Nasal Cavity / drug effects
  • Nasal Cavity / metabolism
  • Neutrophils / drug effects
  • Petasites / chemistry*
  • Plant Extracts / pharmacology*
  • Plant Leaves / chemistry
  • Poly I-C / antagonists & inhibitors
  • Poly I-C / pharmacology
  • Primary Cell Culture
  • STAT Transcription Factors / antagonists & inhibitors*
  • STAT Transcription Factors / genetics
  • STAT Transcription Factors / metabolism
  • Sesquiterpenes / pharmacology*
  • Signal Transduction

Substances

  • Chemokines
  • IL4 protein, human
  • Lipopeptides
  • Pam(3)CSK(4) peptide
  • Plant Extracts
  • STAT Transcription Factors
  • Sesquiterpenes
  • Ze 339
  • Flagellin
  • Interleukin-4
  • Interferon-gamma
  • petasin
  • Poly I-C