PMID- 19508901 OWN - NLM STAT- MEDLINE DCOM- 20100301 LR - 20181201 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 9 IP - 10 DP - 2009 Sep TI - The anti-inflammatory pharmacology of Pycnogenol in humans involves COX-2 and 5-LOX mRNA expression in leukocytes. PG - 1145-9 LID - 10.1016/j.intimp.2009.06.001 [doi] AB - 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. FAU - Canali, Raffaella AU - Canali R AD - National Research Institute for Food and Nutrition, Rome, Italy. canali@inran.it FAU - Comitato, Raffaella AU - Comitato R FAU - Schonlau, Frank AU - Schonlau F FAU - Virgili, Fabio AU - Virgili F LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090607 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Arachidonic Acids) RN - 0 (Flavonoids) RN - 0 (Lipopolysaccharides) RN - 0 (Plant Extracts) RN - 0 (RNA, Messenger) RN - 50JZ5Z98QY (pycnogenols) RN - EC 1.13.11.34 (Arachidonate 5-Lipoxygenase) RN - EC 1.14.99.1 (Cyclooxygenase 1) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 1.14.99.1 (PTGS2 protein, human) RN - EC 3.1.1.4 (Phospholipases A2) SB - IM MH - Adult MH - Anti-Inflammatory Agents/*administration & dosage MH - Arachidonate 5-Lipoxygenase/genetics/immunology/*metabolism MH - Arachidonic Acids/metabolism MH - Cells, Cultured MH - Cyclooxygenase 1/genetics/immunology/metabolism MH - Cyclooxygenase 2/genetics/immunology/*metabolism MH - Female MH - Flavonoids/*administration & dosage MH - Gene Expression Regulation, Enzymologic/drug effects/immunology MH - Humans MH - Lipopolysaccharides/immunology MH - Male MH - Middle Aged MH - Neutrophils/*drug effects/enzymology/immunology/pathology MH - Phospholipases A2/genetics/immunology/metabolism MH - Plant Extracts MH - RNA, Messenger/analysis EDAT- 2009/06/11 09:00 MHDA- 2010/03/02 06:00 CRDT- 2009/06/11 09:00 PHST- 2009/05/04 00:00 [received] PHST- 2009/06/01 00:00 [revised] PHST- 2009/06/01 00:00 [accepted] PHST- 2009/06/11 09:00 [entrez] PHST- 2009/06/11 09:00 [pubmed] PHST- 2010/03/02 06:00 [medline] AID - S1567-5769(09)00195-7 [pii] AID - 10.1016/j.intimp.2009.06.001 [doi] PST - ppublish SO - Int Immunopharmacol. 2009 Sep;9(10):1145-9. doi: 10.1016/j.intimp.2009.06.001. Epub 2009 Jun 7.