Effect of polyphenols extracted from pine bark (pycnogenol) on nitric oxide metabolism and their role in the antioxidant network: Development of tools for the management of free-radical associated diseases?

Proprietary extracts of the bark of Pinus marittima Pycnogenol contain a mixture of flavonoids and condensed polymers which, owing to their intermediate redox potential, can possibly act at the interface between ascorbate and lipophilic antioxidants such as tocopherols and tocotrienols. Ascorbic acid is an integral part of the redox antioxidant-recycling network. Pycnogenol was found effective in markedly extending the ascorbyl radical lifetime by ESR studies, indicating that it can play an important role in the cellular antioxidant redox cycling network. Another important application for flavonoid-containing mixtures is the modulation of NO metabolism. Using as a model for inflammation, macrophages activated by bacterial lipopolysaccharide (LPS) and Interferon-g (INF-g), it was found that Pycnogenol inhibits the large and sustained production of NO. This effect was found to be due to the combination of different biological activities: i) a direct antioxidant scavenging activity of NO, ii) inhibition of the inducible form of nitric oxide synthase (iNOS) activity and iii) inhibition of expression of iNOS. Thus plant polyphenols may be a promising tool for the non-pharmacological control of NO overflow during chronic inflammation and as preventive treatment against different pathologies which have been proposed to be associated with a dysregulation of NO production such as arteriosclerosis, cardiovascular disease and arthritis.