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Moderate wine intake (i.e., 1-2 glasses of wine a day) is associated with a reduced risk of morbidity and mortality from cardiovascular disease. The aim of this study was to evaluate the anti-atherosclerotic effects of a nonalcoholic ethyl acetate fraction (EAF) from a South Brazilian red wine obtained from Vitis labrusca grapes. Experiments were carried out on low-density lipoprotein (LDL) receptor knockout (LDLr⁻/⁻) mice, which were subjected to a hypercholesterolemic diet and treated with doses of EAF (3, 10, and 30 mg/kg) for 12 weeks. At the end of the treatment, the level of plasma lipids, the vascular reactivity, and the atherosclerotic lesions were evaluated. Our results demonstrated that the treatment with EAF at 3 mg/kg significantly decreased total cholesterol, triglycerides, and LDL plus very low-density lipoprotein levels compared with control hypercholesterolemic mice. The treatment of mice with EAF at 3 mg/kg also preserved the vasodilatation induced by acetylcholine on isolated thoracic aorta from hypercholesterolemic LDLr⁻/⁻ mice. This result is in agreement with the degree of lipid deposit on arteries. Taken together, the results show for the first time that the lowest concentration of an EAF obtained from a red wine produced in southern Brazil significantly reduced the progression of atherosclerosis in mice.

A number of studies suggest that moderate consumption of red wine may be more effective than other alcoholic beverages in decreasing the risk of coronary heart disease (CAD). In this study, we investigated the effect of a crude extract (CE), as well as an ethyl acetate fraction (EAF) obtained from a Brazilian red wine in the mesenteric arterial bed (MAB) from rats. Our results showed that after the tonus of MAB was increased with phenylephrine (PE), increasing concentrations of CE induced a concentration-dependent relaxation; moreover, EAF was more potent in relaxing the MAB when compared with CE. In vessels depolarized with KCl (80 mM) or treated with the Na(+)/K(+)-ATPase pump inhibitor, ouabain (OUA; 100 microM), or with the K(+) channel blockers: barium (BaCl(2), 100 microM) and tetraethylammonium (TEA; 500 microM), the effect of EAF was significantly reduced. However, this effect was not altered by the ATP-dependent K(+) (K(ATP)) channel blocker, glibenclamide (GLI; 100 microM) as well as Charybdotoxin (ChTx 10 nM), a nonselective inhibitor of K(Ca) channels of large and intermediate conductance plus Apamin (Apamin 100 nM), a specific inhibitor of K(Ca) channels of small conductance. The residual vasodilator effect of EAF observed in vessels pretreated with L-NOARG (100 microM), 1H-[1,2,4,] oxadiazolo[4,3-alfa]quinoxalin, ODQ (10 microM) or KCl (80 mM), given separately, was reduced by the administration of KCl (40 mM) plus L-NOARG (100 microM). The present study demonstrates that the vasodilator effect of EAF is partially dependent upon membrane hyperpolarization in combination with nitric oxide (NO) release.

This study investigated the superoxide anion and hydroxyl radical scavenger properties, as well as the inhibition of lipid peroxidation by the crude hydroalcoholic extract (CE) and the butanolic (BF) and ethyl acetate (EAF) fractions of Cuphea carthagenensis leaves. In a enzymatic system of O 2 − production (xanthine/xanthine oxidase system) the CE, EAF and BF (0.1–100 μg ml −1 ) were effective at inhibiting both uric acid formation and NBT reduction by O 2 −1 . In the non-enzymatic system of O 2 − generation, the CE and fractions were effective only at the concentration of 100 μg ml −1 . The CE, EAF and BF were also evaluated for their ability to scavenge hydroxyl radicals and/or to chelate iron. The results showed that CE, BF and EAF from C. carthagenensis (0.1–100 μg ml −1 ) were able to inhibit deoxyribose degradation in a concentration-dependent manner. CE was more potent than the fractions. In a hydrophobic system, increasing concentrations of CE, EAF and BF (0.1–100 μg ml −1 ) caused graded inhibition of lipid peroxidation of rat liver homogenate. The EAF displayed the lowest median inhibitory concentration. The present study suggests that an extract (CE) and fractions (EAF and BF) from C. carthagenensis leaves are significant sources of phenolic compounds with antioxidant activity in vitro and may have important health effects, for example, in cardiovascular disease.

This study evaluated the vasorelaxant properties of the crude hydroalcoholic extract (CE) of Cuphea carthagenensis, as well as its butanolic (BF) and ethyl acetate (EA) fractions, in rings of rat thoracic aorta. In endothelium-intact rings contracted with phenylephrine (30-100 nM), cumulative additions of increasing concentrations of CE, BF, and EA of C. carthagenensis (0.1 microg/ml-3 mg/ml) caused graded relaxations, with BF displaying the lowest median inhibitory concentration (IC5; mean, 6.8 microg/ml; 95% confidence limits, 3.3-14.2). BF-induced relaxations of endothelium-intact rings were virtually abolished by prior incubation with the NO-synthase inhibitor N(omega)-nitro-L-arginine (L-NOARG; 10 or 30 microM), and were markedly reduced after guanylate cyclase inhibition with either methylene blue (10 microM) or ODQ (1 microM; 1H[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one). The inhibition of BF-induced relaxation by L-NOARG was prevented to a large extent by simultaneous incubation with L-arginine (1 mM). In endothelium-denuded rings contracted with phenylephrine, CE and BF caused graded relaxations only at doses >100 microg/ml, whereas the NO-donors SNAP (S-nitroso-N-acetyl-penicillamine) and SIN-1 (3-morpholino-sydnonimine) induced full relaxation at 1 microM. BF (100 microg/ml), which caused little relaxation per se of endothelium-denuded rings, potentiated the relaxant effects of SNAP and even more so of SIN-1 (which, unlike SNAP, also releases superoxide anion O2- in addition to NO), in a manner qualitatively similar to that seen with SOD (superoxide dismutase) against SIN-1. These data indicate that the BF of C. carthagenensis induces relaxation of the rat thoracic aorta by two mechanisms: (a) an endothelium-dependent component of action, which clearly depends on the NO/cyclic guanosine monophosphate (cGMP) pathway and can be attributed, at least in part, to free radical-scavenging properties; and (b) an endothelium-independent component of action, which becomes evident at higher doses (> or = 100 microg/ml) and remains to be further characterized. These results suggest that this native South American plant might be beneficial in cardiovascular disease.