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.

Polymeric proanthocyanidins from Sicilian pistachio (Pistacia vera L.) nut extract inhibit lipopolysaccharide-induced inflammatory response in RAW 264.7 cells

“…Partition coefficients measured for proanthocyanidins [51] indicate that molecules at higher polymerization degree are more likely to partition into the lipid phase, which could facilitate interaction with membrane components [52]. Interestingly, in contrast to our findings, proanthocyanidins from grape seeds that exhibited an antiinflammatory activity when co-incubated with activated RAW 264.7 macrophages failed to decrease formation of PGE 2 , when were only pre-incubated [44], suggesting peculiar activities of pistachio proanthocyanidins.…”

“…On the other hand, consistent with our findings, no activity of daidzein in the low micromolar range was observed in the study mentioned before [39]. Anti-inflammatory effects of proanthocyanidins have been reported in rats and mice [41], in human studies [42], as well as in inflammatory cell models [43][44][45]. In our study, HPE proanthocyanidins either oligomers or polymers were found to inhibit the LPS-induced release of NO, Fig.…”

“…Values not sharing the same letter were significantly different (p \ 0.05, Fisher's test) PGE 2 , and TNF-a, with oligomers poorly effective with respect to polymers that contributed almost entirely to the HPE activity. These data may be the reflection of the amounts of proanthocyanidins assayed and/or indicate a different ability of oligomers and polymers to affect the macrophage response, as observed in other researches [44,[46][47][48][49]. To further highlight the role of these components, PF was also found almost effective as the whole HPE in inhibiting phosphorylation, and then activation, of IjB-a.…”

Potential anti-inflammatory, anti-adhesive, anti/estrogenic, and angiotensin-converting enzyme inhibitory activities of anthocyanins and their gut metabolites

“…In our work, and in accordance with other studies (Terra et al 2007), we compared the ability of anthocyanin metabolites to inhibit NO production in macrophages using four different treatment protocols (pre-incubation with polyphenols and activation with LPS alone or LPS plus INF-c, and co-incubation with polyphenols and LPS alone or LPS plus INF-c). When macrophages were co-incubated simultaneously with the test compound and stimulus, protocatechuic acid was found to exhibit the strongest inhibition of NO secretion.…”

Non-extractable Procyanidins and Lignin are Important Factors in the Bile Acid Binding and Radical Scavenging Properties of Cell Wall Material in some Fruits

“…Among the polyphenols, procyanidins (a major group of proanthocyanidins) are found in numerous fruits and fruit products, in the form of polymerized (epi)catechins with varying levels of polymerization. They have been reported to show various biological activities including antioxidant, free radical-scavenging, and anti-carcinogenic activities, inhibition of platelet aggregation [2], and anti-inflammatory activity [3]. Because flavonoids (especially procyanidins) are poorly absorbed, their biological actions may be exerted mainly in the gastrointestinal tract [4], which is also the main site of action of dietary fiber.…”