title: Polymeric proanthocyanidins from Sicilian pistachio (Pistacia vera L.) nut extract inhibit lipopolysaccharide-induced inflammatory response in RAW 264.7 cells.
abstract: BACKGROUND
  Positive effects of pistachio nut consumption on plasma inflammatory biomarkers have been described; however, little is known about molecular events associated with these effects.
  
  
  OBJECTIVE
  We studied the anti-inflammatory activity of a hydrophilic extract from Sicilian Pistacia L. (HPE) in a macrophage model and investigated bioactive components relevant to the observed effects.
  
  
  METHODS
  HPE oligomer/polymer proanthocyanidin fractions were isolated by adsorbance chromatography, and components quantified as anthocyanidins after acidic hydrolysis. Isoflavones were measured by gradient elution HPLC analysis. RAW 264.7 murine macrophages were pre-incubated with either HPE (1- to 20-mg fresh nut equivalents) or its isolated components for 1 h, then washed before stimulating with lipopolysaccharide (LPS) for 24 h. Cell viability and parameters associated with Nuclear Factor-κB (NF-κB) activation were assayed according to established methods including ELISA, Western blot, or cytofluorimetric analysis.
  
  
  RESULTS
  HPE suppressed nitric oxide (NO) and tumor necrosis factor-α (TNF-α) production and inducible NO-synthase levels dose dependently, whereas inhibited prostaglandin E2 (PGE2) release and decreased cyclo-oxygenase-2 content, the lower the HPE amount the higher the effect. Cytotoxic effects were not observed. HPE also caused a dose-dependent decrease in intracellular reactive oxygen species and interfered with the NF-κB activation. Polymeric proanthocyanidins, but not isoflavones, at a concentration comparable with their content in HPE, inhibited NO, PGE2, and TNF-α formation, as well as activation of IκB-α. Oligomeric proanthocyanidins showed only minor effects.
  
  
  CONCLUSIONS
  Our results provide molecular evidence of anti-inflammatory activity of pistachio nut and indicate polymeric proanthocyanidins as the bioactive components. The mechanism may involve the redox-sensitive transcription factor NF-κB. Potential effects associated with pistachio nut consumption are discussed in terms of the proanthocyanidin bioavailability.
authors: Dipartimento STEMBIO, Università di Palermo, Via M. Cipolla 74, 90123, Palermo, Italy.
authors: C
authors: C
authors: Gentile
authors: M
authors: M
authors: Allegra
authors: F
authors: F
authors: Angileri
authors: A M
authors: AM
authors: Pintaudi
authors: M A
authors: MA
authors: Livrea
authors: L
authors: L
authors: Tesoriere
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced; D008070:Lipopolysaccharides / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000187:drug effects; D009754:Nuts / Q000737:chemistry*; D027927:Pistacia / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*; D044945:Proanthocyanidins / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; D044945:Proanthocyanidins; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2