06 May 2014 In Phenolic compounds

We review evidence for and against the 'red wine hypothesis', whereby red wine is more likely to confer cardiovascular benefits than white. As background, there is a strong epidemiological and mechanistic evidence for J-shaped relation between alcohol intake and total mortality. However, epidemiological data favouring a specific benefit of red over white wine are not strong and the 'French paradox' could at least in part be explained by confounding factors. More convincing evidence is that human studies with de-alcoholized red but not white wine show short-term cardiovascular benefits. The specific components of the de-alcoholized wine that are active on cardiovascular endpoints, are the polyphenols found in red wine, especially resveratrol. The effects of resveratrol on isolated tissues or organs are well-described including molecular mechanisms leading to decreased arterial damage, decreased activity of angiotensin-II, increased nitric oxide, and decreased platelet aggregation. Anti-ischaemic effects include stimulation of prosurvival paths, decreased LDL-oxidation, atheroma, and on the ischaemic-beneficial metabolic changes. Most recently, the agonist effect of resveratrol on the anti-senescence factor sirtuin has lessened cell death in myocytes from failing hearts. Mechanistic feasibility strengthens the case for prospective therapeutic trials of alcohol vs. red wine vs. resveratrol, for example in those with heart failure.

06 May 2014 In Phenolic compounds

Several beneficial effects of resveratrol (RES), a natural antioxidant present in red wine have already been described. The aim of our study was to investigate if RES had a clinically measurable cardioprotective effect in patients after myocardial infarction. In this double-blind, placebo controlled trial 40 post-infarction Caucasian patients were randomized into two groups. One group received 10 mg RES capsule daily for 3 months. Systolic and diastolic left ventricular function, flow-mediated vasodilation (FMD), several laboratory and hemorheological parameters were measured before and after the treatment. Left ventricular ejection fraction showed an increasing tendency (ns) by RES treatment. However, left ventricular diastolic function was improved significantly (p < 0.01) by RES. A significant improvement in endothelial function measured by FMD was also observed (p < 0.05). Low-density lipoprotein (LDL) level significantly decreased (p < 0.05) in the RES treated group. Red blood cell deformability decreased and platelet aggregation increased significantly in the placebo group (p < 0.05), while resveratrol treatment has prevented these unfavourable changes. Concerning other measured parameters no significant changes were observed neither in placebo nor in RES group. Our results show that resveratrol improved left ventricle diastolic function, endothelial function, lowered LDL-cholesterol level and protected against unfavourable hemorheological changes measured in patients with coronary artery disease (CAD).

06 May 2014 In Phenolic compounds

The aim of this review is to discuss the accumulating evidence that suggests that grape extracts and purified grape polyphenols possess a diverse array of biological actions and may be beneficial in the prevention of some inflammatory-mediated diseases including cardiovascular disease. The active components from grape extracts, which include the grape seed, grape skin, and grape juice, that have been identified thus far include polyphenols such as resveratrol, phenolic acids, anthocyanins, and flavonoids. All possess potent antioxidant properties and have been shown to decrease low-density lipoprotein-cholesterol oxidation and platelet aggregation. These compounds also possess a range of additional cardioprotective and vasoprotective properties including antiatherosclerotic, antiarrhythmic, and vasorelaxation actions. Although not exclusive, antioxidant properties of grape polyphenols are likely to be central to their mechanism(s) of action, which also include cellular signaling mechanisms and interactions at the genomic level. This review discusses some of the evidence favoring the consumption of grape extracts rich in polyphenols in the prevention of cardiovascular disease. Consumption of grape and grape extracts and/or grape products such as red wine may be beneficial in preventing the development of chronic degenerative diseases such as cardiovascular disease.

06 May 2014 In Phenolic compounds

Misfolded proteins associated with diverse aggregation disorders assemble not only into a single toxic conformer, but rather a suite of aggregated conformers with unique biochemical properties and toxicities. To what extent small molecules can target and neutralize specific aggregated conformers is poorly understood. Therefore, we have investigated the capacity of resveratrol to recognize and remodel five conformers (monomers, soluble oligomers, non-toxic oligomers, fibrillar intermediates and amyloid fibrils) of the Abeta1-42 peptide associated with Alzheimer's disease. We find that resveratrol selectively remodels three of these conformers - soluble oligomers, fibrillar intermediates and amyloid fibrils - into an alternative aggregated species that is non-toxic, high molecular weight and unstructured. Surprisingly, resveratrol does not remodel non-toxic oligomers or accelerate Abeta monomer aggregation, despite that both conformers possess random coil secondary structures indistinguishable from soluble oligomers and significantly different from their beta-sheet rich, fibrillar counterparts. We expect that resveratrol and other small molecules with similar conformational specificity will aid in illuminating the conformational epitopes responsible for Abeta-mediated toxicity.

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