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.
SourceAvailable from: Frank H Comhaire09/2012; 1(3):169-176. DOI:10.1016/S2305-0500(13)60072-X
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ABSTRACT: Many patients with myalgic encephalopathy (fibromyalgia/chronic fatigue syndrome) localise the beginning of their disease at a time period of emotional, or professional, or social stress, or an infectious or traumatic/surgical incident. It is suggested that these may have temporarily suppressed their immunological system, after which a "rebound" of hyper-immunity has occurred. Hyper-immunity against external aggressors is commonly characterized by an extremely high titre of Immunolobulin G against the Epstein-Barr virus (Herpes 4), or elevated Anti-Streptolysin-O titre (ASLO). In a proportion of patients, hyper-immunity proceeds to auto-immunity with IgG antibodies against the thyroid gland (Hashimoto's disease), Antinuclear antibodies (ANF or ANA), and sometimes positive rheumatism-tests. The IgG covalently binds to Complement C3, which complex is cytotoxic by damaging the cell membrane, and induces inflammation. Simultaneously large quantities of reactive oxygen species (ROS) are produced. This causes muscular pain, poor energy production by the mitochondria, and increased permeability of the capillary vessels, also in the brain. The latter disturbs the thalamo-hypothalamo-pituitary regulation, impairs cognitive function, mood and the working memory. It disturbs the nycthemeral rhythm and the sleep pattern, and may cause neuro-vegetative dysfunction. Antibodies against the myelin sheet as well as impaired neurotransmission may be involved in polyneuropathy. Conventional treatment must correct possible endocrine deficiencies and can help alleviating particular symptoms. Causal treatment addresses the immune dysfunction using corticosteroids, gamma globulin infusions, or immune-suppressors. Immune modulators can selectively be attempted. However, treatment should also address the pathogenic mechanisms by prescribing an appropriate diet, and particular food supplements (Complementary and Alternative Medicine, CAM). We have developed a * Frank@comhaire.com; Brakelmeersstraat, 18; B 9830 Sint Martens-Latem; Belgium. Frank H. Comhaire 2 specific nutraceutical containing several anti-oxidants (Astaxanthin, Oxido-reductase ubiquinone Q10), a strong natural anti-inflammatory substance (pine bark extract, Pycnogenol®), the fyto-adaptogen Lepidium meyenii (MACA), acetyl-carnitine, zinc, and vitamins B6, B9 and B12. To this supplement long-chain poly-unsaturated omega-3 fatty acids are added (docosahexaenoic acid, DHA, and eicosapentaenoic acid, EPA). The CAM approach induces and maintains improvement in 85% of patients, but it seldom results in the complete disappearance of signs and symptoms.
Andrologie 01/2005; 15(1):41-47.