The anti-inflammatory pharmacology of Pycnogenol(R) in humans involves COX-2 and 5-LOX mRNA expression in leukocytes

National Research Institute for Food and Nutrition, Rome, Italy.
International immunopharmacology (Impact Factor: 2.47). 07/2009; 9(10):1145-9. DOI: 10.1016/j.intimp.2009.06.001
Source: PubMed


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.

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Available from: Raffaella Canali, Nov 06, 2015
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    • "Downregulation of COX-2 is partially compensated by upregulation of COX-1. Downregulation of 5-lipoxygenase consequently decreases leukotriene levels in asthmatic patients (Canali et al., 2009), and the anti-inflammatory activity of PYC may be best used in combination with inhalation corticosteroids, enabling reduced dosage and frequency of inhalation corticosteroid administration and potentially reducing the need for other asthma medications (Belcaro et al., 2011). Anti-inflammatory properties include alleviating pain and stiffness in arthritis and osteoarthritis patients (Belcaro et al., 2008a), and PYC is a promising antiarthritic drug candidate. "
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    ABSTRACT: Proanthocyanidins are among the most abundant constituents in pine bark extracts (PBEs). This review summarizes medical research on PBEs from Pinus pinaster, Pinus radiata, Pinus massoniana, and other less well-characterized species. The precise mechanisms of the important physiological functions of PBE components remain to be elucidated, but there is evidently great potential for the identification and development of novel antioxidant, anti-inflammatory, cardiovascular, neuroprotective, and anti-cancer medicines. Although toxicological data for PBEs are limited, no serious adverse effects have been reported. PBEs may therefore have potential as nutraceuticals and pharmaceuticals and should be safe for use as food ingredients.
    Full-text · Article · Jan 2015 · Journal of Pharmacology and Experimental Therapeutics
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    • "The extract of the bark of the (meditarranian) pine tree (Pycnogenol®, Horphag, Switserland, 100 mg/day) is rich in anthocyanidins with anti-oxidant effect (Canali et al. 2009), and it reduces inflammatory reaction through the inhibition of the Cyclo-oxygenase (COX) enzymes 1 and 2 (Schäfer et al. 2006) and of the Nuclear Factor kappa B (NFkB )(Grimm et al. 2006). In addition it has a strong anti-oxidant effect and restores the function of the capillary epithelium (Enseleit et al. 2012). "
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    • "As a result monocytes secreted signifi cantly less matrix metalloproteinase MMP-9, which is governed by NF-κB. Another pharmacological study had healthy volunteers take 150 mg Pycnogenol for 5 days (Canali et al., 2009). Neutrophils were isolated from donor's blood and challenged ex vivo to elucidate expression of cyclo-oxygenase (COX) type 1 and type 2, 5-lipoxygenase (5-LOX), 5-lipooxygenase activating protein (FLAP) as well as prostaglandin and leukotrienes synthesis. "
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    ABSTRACT: The potential of Pycnogenol for relieving allergic rhinitis (birch pollen) symptoms was explored in a double-blind, placebo-controlled trial. In 2008 19 subjects started treatment 3 weeks prior to the onset of birch pollen season in Ontario, Canada. While there was an improvement of eye and nasal symptoms with Pycnogenol, there was no significance versus placebo. It was postulated that Pycnogenol may require a lag-time between the start of therapy and the onset of action. Therefore 39 subjects were treated 5-8 weeks prior to the 2009 birch allergy season. The evaluation of subjects in 2009 showed much lower scores for eye (-35%) and nasal (-20.5%) symptoms with Pycnogenol compared with placebo. In succession of the allergy season birch specific IgE increased by 31.9% in the placebo group compared with only 19.4% in the Pycnogenol group. Detailed analysis suggested that symptom-relief was better the longer subjects were on Pycnogenol prior to the allergen exposure. The best results were found with subjects who took Pycnogenol 7-8 weeks ahead of the allergy season. With the limited number of 39 patients statistical predications were unattainable. In conclusion, Pycnogenol improved allergic rhinitis symptoms when supplementation was started at least 5 weeks before the onset of the allergy season.
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