title: Ellagitannins modulate the inflammatory response of human neutrophils ex vivo.
abstract: BACKGROUND
  Tannin-rich plant materials are commonly used in the traditional medicine as external anti-inflammatory, antioxidant and antimicrobial agents. Plant extracts containing significant quantities of tannins are often used in the prevention and treatment of oral cavity diseases such as periodontosis or gingivitis. The contribution of pure ellagitannins to the observed anti-inflammatory activity of tannin-rich remedies is still not resolved.
  
  
  OBJECTIVE
  The aim of the present study the study was to establish if ellagitannins and their precursor - pentagalloylglucose (1) can modulate the inflammatory response of ex-vivo stimulated neutrophils.
  
  
  METHODS
  Human neutrophils were isolated from the buffy coats obtained from healthy volunteers. Neutrophils were cultivated with or without tested compounds. The influence of ellagitannins and 1 on the production and release of pro-inflammatory factors such as elastase, reactive oxygen species, interleukin-8, tumour necrosis factor alpha (TNF-α) and metalloproteinase-9 was evaluated using ELISA sets or chemical methods. The effect on surface expression of toll like receptor 4 (TLR-4) and apoptosis was also checked using flow cytometry.
  
  
  RESULTS
  The results showed that ellgitannins modulate the inflammatory response of human neutrophils by the inhibition of production and release of chosen cytokines and pro-inflammatory enzymes. By the induction of TNF-α ellagitannins enhance neutrophil apoptosis, which is of interest in the case of chronic inflammation within oral cavity. Ellagitannins also decrease the surface expression of TLR-4 in activated neutrophils.
  
  
  CONCLUSIONS
  The results support the traditional use of tannin-rich products in the prevention and treatment of oral cavity diseases. The present study proves the substantial contribution of ellagitannins to the anti-inflammatory activity of tannin-rich medicinal plant materials.
authors.affiliation: Department of Pharmacognosy and Molecular Basis of Phytotherapy, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Granica
authors.affiliation: Department of Pharmacognosy and Molecular Basis of Phytotherapy, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland. Electronic address: jakub.piwowarski@wum.edu.pl.
authors.forename: Jakub P
authors.initials: JP
authors.lastname: Piwowarski
authors.affiliation: Department of Pharmacognosy and Molecular Basis of Phytotherapy, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Kiss
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D007249:Inflammation / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D015394:Molecular Structure; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects*; D010196:Pancreatic Elastase / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; C508606:CXCL8 protein, human; D016207:Cytokines; D047348:Hydrolyzable Tannins; D016209:Interleukin-8; D017382:Reactive Oxygen Species; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C013515:ellagitannin; C435084:pentagalloylglucose; D010196:Pancreatic Elastase; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Ellagitannins; Inflammation; Neutrophils; Oral cavity diseases; Periodontitis