title: Nasturtium (Indian cress, Tropaeolum majus nanum) dually blocks the COX and LOX pathway in primary human immune cells.
abstract: BACKGROUND
  Nasturtium (Indian cress, Tropaeolum majus) is known for its pharmacological value in the treatment of bacterial infections of the upper air tract and urinary bladder. However, scientific data on the anti-inflammatory potency in human-derived cells is missing.
  
  
  OBJECTIVE
  The aim of this study was to investigate the potential of nasturtium to inhibit the lipopolysaccharide (LPS) induced inflammatory response in primary human cells of the immune system.
  
  
  METHODS
  The anti-inflammatory activities of nasturtium and its fractions were evaluated via regulation of arachidonic acid (AA) pathway and MAPK kinase cascade. Fraction H4 which was responsible for the anti-inflammatory effects was further characterized.
  
  
  METHODS
  Human peripheral blood mononuclear cells (PBMC) were either treated with plant extracts or fractions thereof, stimulated with LPS and/or N-formyl-methionyl-leucyl-phenylalanine (fMLP) and analysed for COX and LOX, release of prostaglandin PGE2, leukotriene LTB4, TNF-alpha and ERK signaling pathway activation. The plant extracts were separated into four fractions by HPLC; fraction H4 was subjected to UHPLC-ToF/MS analysis to identify potential bioactive compounds.
  
  
  RESULTS
  We found that aqueous extracts of nasturtium did exert strong concentration dependent suppression of LPS-triggered TNF-alpha release and COX pathway signaling, including PGE2 synthesis. Whereas COX-1 protein expression was not impacted, LPS-triggered COX-2 protein expression was concentration dependently blocked by the plant extract but not COX-2 enzyme activity. These findings suggest a mechanism of action for the plant extract which is different from non-steroidal anti-inflammatory drugs (NSAIDs). Moreover, the plant extract blocked leukotriene LTB4 release, the major end product of the 5-LOX pathway from PBMC. Down-regulation of ERK1/2 and c-Jun activation preceded COX-2 suppression upon plant extract treatment in the presence of LPS. Using HPLC separation of the aqueous extract followed by metabolomic analysis we could limit the number of relevant bioactive compounds in the extract to about 50.
  
  
  CONCLUSIONS
  This study provides a rationale for the anti-inflammatory efficacy of nasturtium observed in man and gives first insight into the underlying molecular mechanisms.
authors.affiliation: University of Freiburg - Medical Center, Institute of Environmental Health Sciences, Molecular Preventive Medicine, Breisacher Strasse 115b, 79106 Freiburg, Germany; University of Freiburg - Medical Center, Institute for Prevention and Cancer Epidemiology, Molecular Preventive Medicine, Elsässerstr. 2, 79110 Freiburg, Germany.
authors.forename: Hoai Thi Thu
authors.initials: HT
authors.lastname: Tran
authors.affiliation: University of Freiburg - Medical Center, Institute of Environmental Health Sciences, Molecular Preventive Medicine, Breisacher Strasse 115b, 79106 Freiburg, Germany.
authors.forename: Melinda-Rita
authors.initials: MR
authors.lastname: Márton
authors.affiliation: University of Freiburg - Medical Center, Institute of Environmental Health Sciences, Molecular Preventive Medicine, Breisacher Strasse 115b, 79106 Freiburg, Germany; University of Freiburg - Medical Center, Institute for Prevention and Cancer Epidemiology, Molecular Preventive Medicine, Elsässerstr. 2, 79110 Freiburg, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Herz
authors.affiliation: Leibniz Institute of Vegetable and Ornamental Crops Grossbeeren/Erfurt e.V., Theodor-Echtermeyer-Weg 1, 14979 Grossbeeren, Germany.
authors.forename: Ronald
authors.initials: R
authors.lastname: Maul
authors.affiliation: Leibniz Institute of Vegetable and Ornamental Crops Grossbeeren/Erfurt e.V., Theodor-Echtermeyer-Weg 1, 14979 Grossbeeren, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Baldermann
authors.affiliation: Leibniz Institute of Vegetable and Ornamental Crops Grossbeeren/Erfurt e.V., Theodor-Echtermeyer-Weg 1, 14979 Grossbeeren, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Schreiner
authors.affiliation: University of Freiburg - Medical Center, Institute of Environmental Health Sciences, Molecular Preventive Medicine, Breisacher Strasse 115b, 79106 Freiburg, Germany; University of Freiburg - Medical Center, Institute for Prevention and Cancer Epidemiology, Molecular Preventive Medicine, Elsässerstr. 2, 79110 Freiburg, Germany. Electronic address: evelyn.lamy@uniklinik-freiburg.de.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Lamy
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced* / Q000188:drug therapy*; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008084:Lipoxygenase / Q000378:metabolism*; D008297:Male; D031223:Nasturtium / Q000737:chemistry; D010936:Plant Extracts / Q000494:pharmacology; D032388:Tropaeolum / Q000737:chemistry
chemical_list: D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D010936:Plant Extracts; D008084:Lipoxygenase; D051546:Cyclooxygenase 2
keywords: Anti-inflammatory effect in primary human PBMC; Cyclooxygenase-2; Isothiocyanates; LTB4; Nasturtium; PGE(2)