Procyanindin extract (PE) is a mixture of polyphenols, mainly procyanidins, obtained from grape seedwith putative antiinflammatory activity. We evaluated the PE effect on RAW 264.7 macrophagesstimulated with lipopolysaccharide plus interferon-
that show a rapid enhanced production ofprostaglandin E
2 (PGE
2) and nitric oxide (NO). Our results demonstrated that PE significantly inhibitedthe overproduction of NO, dose and time dependently. PE caused a marked inhibition of PGE
2synthesis when administered during activation. Moreover, PE pretreatment diminished iNOS mRNAand protein amount dose dependently (10-65
g/mL). PE (65
g/mL) pretreatment inhibited NF
B(p65) translocation to nucleus by nearly 40%. Trimeric and longer oligomeric-rich procyanidin fractionsfrom PE (5-30
g/mL) inhibited iNOS expression but not the monomeric forms catechin andepicatechin. Thus, we show that the degree of polymerization is important in determining procyanidineffects. PE was considerably a more effective inhibitor of NO biosynthesis (IC
50 = 50
g/mL) incomparison to other antiinflammatories, such as aspirin (3 mM), indomethacin (20
M), anddexamethasone (9 nM). In conclusion, PE modulates inflammatory response in activated macrophagesby the inhibition of NO and PGE
2 production, suppression of iNOS expression, and NFkB translocation.These results demonstrate an immunomodulatory role of grape seed procyanidins and thus a potentialhealth-benefit in inflammatory conditions that exert an overproduction of NO and PGE
2.