National Research Institute for Food and Nutrition, Rome, Italy.
Int Immunopharmacol. 2009 Sep;9(10):1145-9. doi: 10.1016/j.intimp.2009.06.001. Epub 2009 Jun 7.
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.
我们研究了碧萝芷补充剂对人类多形核白细胞（PMN）花生四烯酸途径的影响，以响应炎症刺激。碧萝芷是一种标准化的法国沿海松树皮提取物，由原花青素和多酚单体组成。年龄在 35 至 50 岁之间的健康志愿者每天补充 150 毫克碧萝芷，持续五天。在最后一天补充前后，抽取血液并分离 PMN。PMN 用脂多糖（LPS）预先刺激，并通过受体介导的激动剂甲酰基-甲硫氨酸-亮氨酸-苯丙氨酸（fMLP）刺激，以激活花生四烯酸途径和白三烯、血栓素和前列腺素的生物合成。碧萝芷补充剂抑制 5-脂氧合酶（5-LOX）和环氧化酶-2（COX-2）基因表达和磷脂酶 A2（PLA2）活性。这种作用与 COX-1 基因表达的代偿性上调有关。有趣的是，碧萝芷暂停了 5-LOX 和 5-脂氧合酶激活蛋白（FLAP）表达之间的相互依存关系。碧萝芷补充剂减少了白三烯的产生，但没有使前列腺素不受影响，我们将其归因于 COX-2 活性下降有利于 COX-1。在这里，我们首次表明，碧萝芷补充剂同时抑制 COX-2 和 5-LOX 基因表达，并减少人类 PMN 在体外炎症刺激下的白三烯生物合成。
