Anti-inflammatory compound resveratrol suppresses homocysteine formation in stimulated human peripheral blood mononuclear cells in vitro.
ABSTRACT Inflammation, immune activation and oxidative stress play a major role in the pathogenesis of cardiovascular disorders. In addition to markers of inflammation, moderate hyperhomocysteinemia is an independent risk factor for cardiovascular disease, and there is a link between the activation of immunocompetent cells and the enhanced formation of homocysteine in vitro. Likewise, anti-inflammatory drugs and nutrients rich in antioxidant vitamins are able to reduce cardiovascular risk and to slow down the atherogenic process. Resveratrol, a phenolic antioxidant synthesized in grapes and vegetables and present in wine, has also been supposed to be beneficial for the prevention of cardiovascular events. Apart from its strong antioxidant properties, resveratrol has also been demonstrated to act as an anti-inflammatory agent. In this study the influence of resveratrol on the production of homocysteine by stimulated human peripheral blood mononuclear cells (PBMCs) was investigated. Results were compared to earlier described effects of the anti-inflammatory compounds aspirin and salicylic acid and of the lipid-lowering drug atorvastatin. Stimulation of PBMCs with the mitogens concanavalin A and phytohemagglutinin induced significantly higher homocysteine accumulation in supernatants compared with unstimulated cells. Treatment with 10-100 muM resveratrol suppressed homocysteine formation in a dose-dependent manner. Resveratrol did not influence the release of homocysteine from resting PBMCs. The data suggest that resveratrol may prevent homocysteine accumulation in the blood by suppressing immune activation cascades and the proliferation of mitogen-driven T-cells. The effect of resveratrol to down-regulate the release of homo-cysteine was comparable to the decline of neopterin concentrations in the same experiments. The suppressive effect of resveratrol was very similar to results obtained earlier with aspirin, salicylic acid and atorvastatin; however, it appeared that doses of compounds needed to reduce homocysteine levels to 50% of stimulated cells were always slightly lower than those necessary to achieve the same effect on neopterin concentrations. The influence of resveratrol and of all the other compounds on homocysteine production appears to be independent of any direct effect on homocysteine biochemistry.
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ABSTRACT: Unregulated uptake of oxidized low-density lipoproteins (ox-LDL) via macrophage scavenger receptors (SRs) such as lectin-like ox-LDL receptor-1 (LOX-1) is a key event in atherosclerosis. In this study, we examined the effects of five selected food phytochemicals on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced LOX-1 mRNA expression in THP-1 human monocyte-like cells. Nobiletin, a citrus polymethoxylated flavone, markedly reduced it in dose- and time-dependent manners. It also suppressed the phosphorylation of extracellular signal-regulated protein kinase (ERK) 1/2, c-Jun NH2-terminal kinase (JNK) 1/2, and c-Jun (Ser-63), thereby inhibiting the transcriptional activity of activator protein-1. Further nobiletin attenuated expression of SR-A, SR-PSOX, CD36, and CD68, but not CLA-1, mRNA, leading to the blockade of DiI-acLDL uptake. Together, our results suggest that nobiletin is a promising phytochemical for regulating atherosclerosis with reasonable action mechanisms.FEBS Letters 06/2006; 580(13):3321-8. DOI:10.1016/j.febslet.2006.04.077 · 3.34 Impact Factor
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ABSTRACT: Korean raspberry, Rubus coreanus Miquel (RCM), contains high concentrations of phenolic compounds, which prevent oxidative stress. To determine the effect of RCM on antioxidant capacity in humans, we assessed in vivo lipid oxidation and antioxidant enzyme activities from plasma in 15 healthy men. The subjects ingested 30 g of freeze-dried RCM daily for 4 weeks. Blood was taken at baseline and at the end of the study to determine blood lipid profiles, fasting plasma glucose, liver function, lipid peroxidation, and antioxidant enzyme activities. RCM supplementation had no effect on blood lipid or fasting plasma glucose concentrations but decreased alkaline phosphatase activity. RCM supplementation increased glutathione peroxidase activities (P < 0.05) but had no effect on lipid peroxidation. These results suggest that short-term RCM supplementation may offer health benefits by enhancing antioxidant capacity in a healthy population.Nutrition research and practice 10/2011; 5(5):429-34. DOI:10.4162/nrp.2011.5.5.429 · 1.13 Impact Factor
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ABSTRACT: Resveratrol (3,4',5-trihydroxystilben), a phenolic antioxidant synthesized in grapes and other plants, and also present in wine, has been suggested to help prevent cardiovascular events. In this study the influence of resveratrol on platelet aggregation during a model of hyperhomocysteinemia was investigated. We induced hyperhomocysteinemia using a reduced form of Hcys (final dose, 0.1 mM) and the most reactive form of Hcys, its cyclic thioester, homocysteine thiolactone (HTL, 1 µM). The aim of our study in vitro was also to investigate superoxide anion radical (O(2)(-)) generation after incubation of platelets with Hcys, HTL, and resveratrol. We have observed that HTL, like its precursor Hcys, stimulated the generation of (O(2)(-) in platelets and caused an augmentation of platelet aggregation induced by the strong physiological agonist thrombin. Our results in vitro also demonstrated that resveratrol reduced the toxic action of Hcys and HTL on blood platelet aggregation and superoxide anion radical production in platelets, suggesting its potential protective effects on hemostasis are negatively influenced by homocysteine and its derivatives.Platelets 06/2011; 22(4):277-83. DOI:10.3109/09537104.2010.550349 · 2.63 Impact Factor