Anti-inflammatory compound resveratrol suppresses homocysteine formation in stimulated human peripheral blood mononuclear cells in vitro

Division of Biological Chemistry, Biocentre, Innsbruck Medical University, and Ludwig Boltzmann Institute of AIDS-Research, Innsbruck, Austria.
Clinical Chemistry and Laboratory Medicine (Impact Factor: 2.71). 02/2005; 43(10):1084-8. DOI: 10.1515/CCLM.2005.189
Source: PubMed


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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    • "Moreover, on the basis of various observations, it is proposed that Hcy and HTL may act as oxidants in the model system in vitro and in vivo (Carluccio et al., 2007; Olas et al., 2008), but some dietary polyphenolic antioxidants can attenuate the oxidative damage, induced by hyperhomocysteinemia (Carluccio et al., 2007). A variety of well-known antioxidants, including polyphenolic antioxidants, have been shown to exert a protective action against Hcy toxicity (Schoecksnadel et al., 2005; Carluccio et al., 2007; Noll et al., 2009a; 2009b). However , the mechanisms of protection provided by many exogenous compounds against Hcy action are still unknown . "
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    ABSTRACT: Elevated concentration of homocysteine (Hcy) in human tissues, definied as hyperhomocysteinemia has been correlated with some diseases, such as cardiovascular, neurodegenerative, and kidney disorders. Homocysteine occurs in human blood plasma in several forms, including the most reactive one, the homocysteine thiolactone (HTL) - a cyclic thioester, which represents up to 0.29% of total plasma Hcy. In the article, the effects of hyperhomocysteinemia on the complex process of hemostasis, which regulates the flowing properties of blood, are described. Possible interactions of homocysteine and its different derivatives, including homocysteine thiolactone, with the major components of hemostasis such as endothelial cells, blood platelets, plasmatic fibrinogen and plasminogen, are also discussed. Modifications of hemostatic proteins (N-homocysteinylation or S-homocysteinylation) induced by Hcy or its thiolactone seem to be the main cause of homocysteine biotoxicity in hemostatic abnormalities. It is suggested that Hcy and HTL may also act as oxidants, but various polyphenolic antioxidants are able to inhibit the oxidative damage induced by Hcy or HTL. We also discuss the role of phenolic antioxidants in hyperhomocysteinemia -induced changes in hemostasis.
    Acta biochimica Polonica 05/2012; 59(2):185-94. · 1.15 Impact Factor
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    • "Among the antioxidants in fruits and vegetables, the health benefits of phenolic compounds have been studied, because of their high quantities and antioxidant capacity. High phenolic compound-containing foods such as fruits, teas, and wines increase plasma antioxidant capacity and reduce inflammation, cardiovascular disease, and tumorigenesis [23-28]. Recent studies have also shown that berries such as strawberries, cranberries and blueberries are good sources of phenolic compounds and dietary fiber, and that a high intake of berries increases antioxidant capacity and prevents atherosclerosis and hepatic fibrosis in human and animal studies [29-33]. "
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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 · 1.44 Impact Factor
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    • "trans-Resveratrol 3-b-glucoside persulfate (15) was the most potent in prolonging the clotting times and was selected for this study due to the cardiovascular effects of trans-resveratrol. The mechanism of action of trans-resveratrol, although is not fully understood [25], seems to be related to the inhibition of the induction of TF expression in endothelial cells and mononuclear cells [26] and/or to preventing homocysteine accumulation in the blood [27]. High levels of homocysteine (hyperhomocysteinemia) increase the risk of atherosclerosis and thrombosis, although the mechanism by which hyperhomocysteinemia might contribute to in vivo atherogenesis and thrombogenesis are scarcely understood. "
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    ABSTRACT: A new series of persulfated compounds was synthesized and assayed for in vitro anticoagulant and antiplatelet activities, which may be useful in the treatment of both venous and arterial thrombosis. Persulfation of polyphenolic components of wine, coumarins and other structurally diverse small molecules was achieved with triethylamine-sulphur trioxide adduct. The derivatives were highly effective in increasing the APTT, being trans-resveratrol 3-ß-D-glucopyranoside persulfate (15) the most potent (APTT2=1.5×10(-4) M), and were able to completely block the clotting process at the highest concentration. Compound 15 showed good stability in human plasma and anticoagulation effects in whole blood. trans-Resveratrol 3-ß-D-glucopyranoside persulfate (15) and a series of polysulfated oligoflavonoids (1-4) also exhibited antiplatelet activity by inhibition of arachidonic acid and ADP-induced platelet aggregation.
    European Journal of Medicinal Chemistry 03/2011; 46(6):2347-58. DOI:10.1016/j.ejmech.2011.03.016 · 3.45 Impact Factor
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