Procyanidins extracted from Pinus maritima (Pycnogenol): scavengers of free radical species and modulators of nitrogen monoxide metabolism in activated murine RAW 264.7 macrophages.
Nitrogen monoxide (NO) has diverse physiological roles and also contributes to the immune defense against viruses, bacteria, and other parasites. However, excess production of NO is associated with various diseases such arthritis, diabetes, stroke, septic shock, autoimmune, chronic inflammatory diseases, and atheriosclerosis. Cells respond to activating or depressing stimuli by enhancing or inhibiting the expression of the enzymatic machinery that produce NO. Thus, maintenance of a tight regulation of NO production is important for human health. Phytochemicals have been traditionally utilized in ways to treat a family of pathologies that have in common the disregulation of NO production. Here we report the scavenging activity of Pycnogenol (the polyphenols containing extract of the bark from Pinus maritima) against reactive oxygen and nitrogen species, and its effects on NO metabolism in the murine macrophages cell line RAW 264.7. Macrophages were activated by the bacterial wall components lipopolysaccharide (LPS) and interferon (IFN-gamma), which induces the expression of large amounts of the enzyme nitric oxide synthase (iNOS). Preincubation of cells with physiological concentrations of Pycnogenol significantly decreased NO generation. It was found that this effect was due to the combination of several different biological activities, i.e., its ROS and NO scavenging activity, inhibition of iNOS activity, and inhibition of iNOS-mRNA expression. These data begin to provide the basis for the conceptual understanding of the biological activity of Pycnogenol and possibly other polyphenolic compounds as therapeutic agents in various human disorders.
Virgili
F
F
Department of Molecular and Cell Biology, University of California, Berkeley 94720-3200, USA.
Kobuchi
H
H
Packer
L
L
D000818:Animals; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism; D050856:Interferon Regulatory Factor-1; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010936:Plant Extracts; D012333:RNA, Messenger / Q000235:genetics; D013481:Superoxides / Q000378:metabolism; D014197:Trees / Q000737:chemistry
D000975:Antioxidants; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D005419:Flavonoids; D016166:Free Radical Scavengers; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; D016328:NF-kappa B; D009566:Nitrates; D009573:Nitrites; D010750:Phosphoproteins; D010936:Plant Extracts; D012333:RNA, Messenger; D013481:Superoxides; D009569:Nitric Oxide; D017665:Hydroxyl Radical; C024070:pycnogenols; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse