학술논문
The anti-inflammatory pharmacology of Pycnogenol.sup.[R] in humans involves COX-2 and 5-LOX mRNA expression in leukocytes
Document Type
Report
Source
International Immunopharmacology. Sept, 2009, Vol. 9 Issue 10, p1145, 5 p.
Subject
Language
English
ISSN
1567-5769
Abstract
To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.intimp.2009.06.001 Byline: Raffaella Canali (a), Raffaella Comitato (a), Frank Schonlau (b), Fabio Virgili (a) Keywords: Flavonoids; 5-LOX; COX-2; Gene expression Abstract: We investigated the effects of Pycnogenol.sup.[R] 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. Author Affiliation: (a) National Research Institute for Food and Nutrition, via Ardeatina 546, 0178 Rome, Italy (b) Horphag Research (UK) Ltd. 28 Old Brompton Road Suite 393; South Kensington, London SW7 3SS UK Article History: Received 4 May 2009; Revised 1 June 2009; Accepted 1 June 2009