Journal
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
Volume 55, Issue 11, Pages 4357-4365Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jf0633185
Keywords
procyanidins; dimers; trimers; lipopolysaccharide; INF-gamma; RAW 264.7; NO; iNOS; PGE(2); NF kappa B; p65
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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 E-2 (PGE(2)) 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 PGE(2) synthesis when administered during activation. Moreover, PE pretreatment diminished iNOS mRNA and protein amount dose dependently (10-65 mu g/mL). PE (65 mu g/mL) pretreatment inhibited NF kappa B (p65) translocation to nucleus by nearly 40%. Trimeric and longer oligomeric-rich procyanidin fractions from PE (5-30 mu g/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 mu g/mL) in comparison to other antiinflammatories, such as aspirin (3 mM), indomethacin (20 mu M), and dexamethasone (9 nM). In conclusion, PE modulates inflammatory response in activated macrophages by 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 potential health-benefit in inflammatory conditions that exert an overproduction of NO and PGE(2).
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