title: The anti-inflammatory pharmacology of Pycnogenol in humans involves COX-2 and 5-LOX mRNA expression in leukocytes.
abstract: We investigated the effects of Pycnogenol supplementation on the arachidonic acid pathway in human polymorphonuclear leukocytes (PMNL) in response to an inflammatory stimulus. Pycnogenol is a standardised extract of French maritime pine bark consisting of procyanidins and polyphenolic monomers. Healthy volunteers aged 35 to 50 years were supplemented with 150 mg Pycnogenol a day for five days. Before and after the final day of supplementation, blood was drawn and PMNL were isolated. PMNL were primed with lipopolysaccharide (LPS) and stimulated with the receptor-mediated agonist formyl-methionyl-leucyl-phenylalanine (fMLP) to activate the arachidonic acid pathway and the biosynthesis of leukotrienes, thromboxane and prostaglandins. Pycnogenol supplementation inhibited 5-lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2) gene expression and phospholipase A2 (PLA2) activity. This effect was associated with a compensatory up-regulation of COX-1 gene expression. Interestingly, Pycnogenol suspended the interdependency between 5-LOX and 5-lipoxygenase activating protein (FLAP) expression. Pycnogenol supplementation reduced leukotriene production but did not leave prostaglandins unaltered, which we attribute to a decline of COX-2 activity in favour of COX-1. Here we show for the first time that Pycnogenol supplementation simultaneously inhibits COX-2 and 5-LOX gene expression and reduces leukotriene biosynthesis in human PMNL upon pro-inflammatory stimulation ex vivo.
authors.affiliation: National Research Institute for Food and Nutrition, Rome, Italy. canali@inran.it
authors.forename: Raffaella
authors.initials: R
authors.lastname: Canali
authors.forename: Raffaella
authors.initials: R
authors.lastname: Comitato
authors.forename: Frank
authors.initials: F
authors.lastname: Schonlau
authors.forename: Fabio
authors.initials: F
authors.lastname: Virgili
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001095:Arachidonic Acids / Q000378:metabolism; D002478:Cells, Cultured; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000276:immunology; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D054467:Phospholipases A2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010936:Plant Extracts; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D000893:Anti-Inflammatory Agents; D001095:Arachidonic Acids; D005419:Flavonoids; D008070:Lipopolysaccharides; D010936:Plant Extracts; D012333:RNA, Messenger; C024070:pycnogenols; D001094:Arachidonate 5-Lipoxygenase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D054467:Phospholipases A2