title: Additive, antagonistic, and synergistic effects of procyanidins and polyunsaturated fatty acids over inflammation in RAW 264.7 macrophages activated by lipopolysaccharide.
abstract: OBJECTIVE
  Macrophages play an important role in immunogenic challenges and can aggravate and propagate local inflammation. Nuclear factor-kappa B (NF-κB) and activator protein 1 pathways can regulate these inflammatory processes by modulating expression of proinflammatory genes. Bioactive molecules present in food, such as procyanidins and polyunsaturated fatty acids, possess antiinflammatory effects in vivo and in vitro. Our aim was to assess whether they have synergistic antiinflammatory effects in murine macrophages.
  
  
  METHODS
  A nitric oxide production assay, a phosphoprotein assay, and a low-density array for 91-gene expression related to inflammation, oxidative stress, and metabolism were performed to assess the synergistic antiinflammatory effects of dimeric procyanidins (B1, B2, B3, B4) (5 μg/mL), and the polyunsaturated fatty acids, docosahexaenoic acid, and eicosapentaenoic acid (30 μM) coincubated with lipopolysaccharide for 19 h to mimic inflammation in RAW 264.7 macrophages (mouse leukaemic monocyte macrophage cell line).
  
  
  RESULTS
  Adding eicosapentaenoic acid plus B3 had synergistic effects leading to decreased nitric oxide levels; the modulation of phosphoprotein levels, such as P-nuclear factor-[kappa] B p65 and P-stress-activated protein kinase/Jun-amino-terminal kinase; the down-regulation of proinflammatory genes, such as interleukins, chemokines, transcription factors; and up-regulation of antioxidant genes.
  
  
  CONCLUSIONS
  This combination has a stronger antiinflammatory effect than either of these molecules separately in RAW macrophages. These results could lead to in vivo studies that may yield novel preventive or palliative nutritional treatments for obesity, atherosclerosis, and cardiovascular diseases.
authors.affiliation: Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: Victor
authors.initials: V
authors.lastname: Pallarès
authors.forename: Damien
authors.initials: D
authors.lastname: Calay
authors.forename: Lídia
authors.initials: L
authors.lastname: Cedó
authors.forename: Anna
authors.initials: A
authors.lastname: Castell-Auví
authors.forename: Martine
authors.initials: M
authors.lastname: Raes
authors.forename: Montserrat
authors.initials: M
authors.lastname: Pinent
authors.forename: Anna
authors.initials: A
authors.lastname: Ardévol
authors.forename: Lluís
authors.initials: L
authors.lastname: Arola
authors.forename: Mayte
authors.initials: M
authors.lastname: Blay
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000378:metabolism; D004041:Dietary Fats / Q000494:pharmacology / Q000627:therapeutic use; D004347:Drug Interactions; D015118:Eicosapentaenoic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D005786:Gene Expression Regulation; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics; D018836:Inflammation Mediators / Q000378:metabolism*; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D044945:Proanthocyanidins / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D004041:Dietary Fats; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D010936:Plant Extracts; D044945:Proanthocyanidins; D009569:Nitric Oxide; D015118:Eicosapentaenoic Acid