title: Grape-seed procyanidins act as antiinflammatory agents in endotoxin-stimulated RAW 264.7 macrophages by inhibiting NFkB signaling pathway.
abstract: Procyanindin extract (PE) is a mixture of polyphenols, mainly procyanidins, obtained from grape seed with putative antiinflammatory activity. We evaluated the PE effect on RAW 264.7 macrophages stimulated with lipopolysaccharide plus interferon-gamma that show a rapid enhanced production of prostaglandin E2 (PGE2) and nitric oxide (NO). Our results demonstrated that PE significantly inhibited the overproduction of NO, dose and time dependently. PE caused a marked inhibition of PGE2 synthesis when administered during activation. Moreover, PE pretreatment diminished iNOS mRNA and protein amount dose dependently (10-65 microg/mL). PE (65 microg/mL) pretreatment inhibited NFkappaB (p65) translocation to nucleus by nearly 40%. Trimeric and longer oligomeric-rich procyanidin fractions from PE (5-30 microg/mL) inhibited iNOS expression but not the monomeric forms catechin and epicatechin. Thus, we show that the degree of polymerization is important in determining procyanidin effects. PE was considerably a more effective inhibitor of NO biosynthesis (IC50 = 50 microg/mL) in comparison to other antiinflammatories, such as aspirin (3 mM), indomethacin (20 microM), and dexamethasone (9 nM). In conclusion, PE modulates inflammatory response in activated macrophages by the inhibition of NO and PGE2 production, suppression of iNOS expression, and NFkB translocation. These results demonstrate an immunomodulatory role of grape seed procyanidins and thus a potential health-benefit in inflammatory conditions that exert an overproduction of NO and PGE2.
authors.affiliation: Department of Biochemistry and Biotechnology, Unitat d'Enologia del Centre de Referència en Tecnologia dels Aliments de la Generalitat de Catalunya, Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: Ximena
authors.initials: X
authors.lastname: Terra
authors.forename: Josep
authors.initials: J
authors.lastname: Valls
authors.forename: Xavier
authors.initials: X
authors.lastname: Vitrac
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Mérrillon
authors.forename: Lluís
authors.initials: L
authors.lastname: Arola
authors.forename: Anna
authors.initials: A
authors.lastname: Ardèvol
authors.forename: Cinta
authors.initials: C
authors.lastname: Bladé
authors.forename: Juan
authors.initials: J
authors.lastname: Fernandez-Larrea
authors.forename: Gerard
authors.initials: G
authors.lastname: Pujadas
authors.forename: Josepa
authors.initials: J
authors.lastname: Salvadó
authors.forename: Mayte
authors.initials: M
authors.lastname: Blay
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D056604:Grape Seed Extract; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D044945:Proanthocyanidins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; D016328:NF-kappa B; D010936:Plant Extracts; D044945:Proanthocyanidins