title: Effects of Geum urbanum L. root extracts and its constituents on polymorphonuclear leucocytes functions. Significance in periodontal diseases.
abstract: BACKGROUND
  Geum urbanum L. (wood avens) root infusions and decoctions have been used externally for reducing the bleeding and inflammation of gums (gingivitis), and mucous membranes.
  
  
  OBJECTIVE
  Taking into account that primed and hyperactivated neutrophils are an important factor in the transition from gingivitis to periodontitis, we investigated the effects of phytochemically characterised (HPLC-DAD-MS(n)) extracts of different polarity from Geum urbanum root on oxidative burst, elastase, metalloproteinase 9 (MMP-9), interleukin 8 (IL-8) and 1β (IL-1β), tumour necrosis factor (TNF-α) release, expression of adhesion molecules (CD62L and CD11b) and delayed apoptosis in stimulated neutrophils. As gemin A is a dominating compound in a raw material, so we considered its activity in parallel with the positive control quercetin.
  
  
  METHODS
  The extracts were characterised by HPLC-DAD- MS(n) method. The inhibition of ROS production by stimulated neutrophils was determined using luminol dependent chemiluminescence method. The effect on MMP-9, IL-1β, TNF-α and IL-8 production by neutrophils was measured by enzyme-linked immunosorbent assay (ELISA). Neutrophil elastase release was established spectrophotometrically. The expression of adhesion molecules and the apoptosis of neutrophils was analyzed with flow cytometry.
  
  
  RESULTS
  The main compounds detected in the extract belong mainly to the group of ellagitannin: pedunculagin, stachyurin, casuarynin and gemin A, and ellagic acid derivatives. Procyanidins and one complex tannin were found as minor compounds. Gemin A significantly affected the functions of stimulated neutrophils by reducing the surface expression of CD11b, and inhibiting the release of reactive oxygen species, and proteases (elastase, MMP-9), chemokines and cytokines (interleukins IL-8, IL-1β). Interestingly, gemin A stimulated the release of TNF-α, which may be one of the stimulators of apoptosis of neutrophil cells. The primary aqueous extract, the ethyl acetate and the butanolic fractions, all containing the highest level of gemin A, have exerted similar but weaker activity.
  
  
  CONCLUSIONS
  The modulating effect on the neutrophils function of extracts, and its main constituent gemin A, support the traditional use of this plant material in cavity inflammation including mucositis, gingivitis and periodontosis.
authors.affiliation: Department of Pharmacognosy and Molecular Basis of Phytotherapy, Medical University of Warsaw, Banacha 1, Warsaw 02-097, Poland.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Granica
authors.affiliation: Department of Pharmacognosy and Molecular Basis of Phytotherapy, Medical University of Warsaw, Banacha 1, Warsaw 02-097, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Kłębowska
authors.affiliation: Department of Pharmacognosy and Molecular Basis of Phytotherapy, Medical University of Warsaw, Banacha 1, Warsaw 02-097, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Kosiński
authors.affiliation: Department of Pharmacognosy and Molecular Basis of Phytotherapy, Medical University of Warsaw, Banacha 1, Warsaw 02-097, Poland.
authors.forename: Jakub P
authors.initials: JP
authors.lastname: Piwowarski
authors.affiliation: Physical Chemistry Department, Medical University of Warsaw, Banacha 1, Warsaw 02-097, Poland; Centre of Molecular and Macromolecular Studies PAS, Sienkiewicza 112, Lodz 90-363, Poland.
authors.forename: Marta K
authors.initials: MK
authors.lastname: Dudek
authors.affiliation: Centre of Molecular and Macromolecular Studies PAS, Sienkiewicza 112, Lodz 90-363, Poland.
authors.forename: Sławomir
authors.initials: S
authors.lastname: Kaźmierski
authors.affiliation: Department of Pharmacognosy and Molecular Basis of Phytotherapy, Medical University of Warsaw, Banacha 1, Warsaw 02-097, Poland. Electronic address: akiss@wum.edu.pl.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Kiss
mesh_terms: D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D031986:Geum / Q000737:chemistry*; D005891:Gingivitis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D019272:Leukocyte Elastase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D013058:Mass Spectrometry; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D052016:Mucositis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D010510:Periodontal Diseases / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D010518:Periodontitis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D018517:Plant Roots / Q000737:chemistry*; D010946:Plants, Medicinal; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D019272:Leukocyte Elastase; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Coriariin B (PubChem CID: 16130319); Ellagitannins; Gemin A; Gemin A (PubChem CID: 16129624); Geum urbanum L.; Gingivitis; Inflammation; Neutrophil; Valoneic Acid Dilacton (PubChem CID: 10151874); Vanillic Acid (PubChem CID: 8468)