While the number of publications on wine and health is steadily increasing, ranging from a molecular level to epidemiological studies, often with contradictory results, little attention has been given to a holistic approach to research, starting from the molecular level to arrive at pharmacological and medical conclusions. In this review, some unusual concepts are considered, such as the phytocomplex, the vehicle, and the Matrix effect. The concept of the phytocomplex is discussed, specifically the biological activities of Tyrosol, Hydroxytyrosol, and Resveratrol; indeed, the interactions among different molecules in herbal matrices provide a specific response. This is often markedly different from the response evoked by single constituents in the modulation of microbial populations in the gut, in intestinal stability and bioaccessibility, and, obviously, in inducing biological responses. Among the many alcoholic beverages which contain these molecules, wine has the most peculiar Matrix effect, which can heavily influence the bioavailability of the phytocomplex obtained by the fermentation processes that produce this beverage. Wine’s Matrix effect plays an instrumental role in improving the beneficial compounds’ bioavailability and/or in inhibiting alcohol metabolites’ carcinogenicity. Underestimation of the wine Matrix effect could lead to deceiving results, as in the case of dealcoholized wine or wine-compound-based nutritional supplements; alternatively, this can occur in the emphasis of a single component’s toxic activity, in this case, alcohol, ignoring the specific molecular-level protective action of other compounds (polyphenols) that are present in the same matrix. The dark side of the Matrix effect is also discussed. This review confirms the research recommendations made by the WHO Scientific Group, which suggests it is important “to investigate the possible protective effects of ingredients other than alcohol in alcoholic beverages”, considering that most recent studies seem not only relevant but also capable of directing future research towards innovative points of view that have so far been too neglected.

Background: The importance of polyphenols in human health is well known; these compounds are common in foods, such as fruits, vegetables, spices, extra virgin olive oil and wine. On the other hand, the different factors that modulate the biological activity of these compounds are less well known. Conceptualization of the work: In this review we took into account about 200 relevant and recent papers on the following topics: “polyphenols bioavailability”, “polyphenols matrix effect”, “food matrix effect”, “polyphenols-cytochromes interaction”, after having reviewed and updated information on chemical classification and main biological properties of polyphenols, such as the antioxidant, anti-radical and anti-inflammatory activity, together with the tricky link between in vitro tests and clinical trials. Key findings: the issue of polyphenols bioavailability and matrix effect should be better taken into account when health claims are referred to polyphenols, thus considering the matrix effect, enzymatic interactions, reactions with other foods or genetic or gender characteristics that could interfere. We also discovered that in vitro studies often underrate the role of phytocomplexes and thus we provided practical hints to describe a clearer way to approach an investigation on polyphenols for a more resounding transfer to their use in medicine.

Several studies have suggested a possible relationship between polymorphic variants of the taste receptors genes and the acceptance, liking and intake of food and beverages. In the last decade investigators have attempted to link the individual ability to taste 6-n-propylthiouracil (PROP) and the sensations, such as astringency and bitterness, elicited by wine or its components, but with contradictory results. We have used the genotype instead of the phenotype (responsiveness to PROP or other tastants), to test the possible relation between genetic variability and the perception of wine characteristic in 528 subjects from Italy and the Czech Republic. We observed several interesting associations, among which the association between several TAS2R38 gene single nucleotide polymorphisms (P = 0.002) and the TAS2R16-rs6466849 polymorphism with wine sourness P = 0.0003). These associations were consistent in both populations, even though the country of origin was an important factor in the two models, thus indicating therefore that genetics alongside cultural factors also play a significant role in the individual liking of wine.

Introduction Several studies demonstrated that endothelium dependent vasodilatation is impaired in cardiovascular and chronic kidney diseases because of oxidant stress-induced nitric oxide availability reduction. The Mediterranean diet, which is characterized by food containing phenols, was correlated with a reduced incidence of cardiovascular diseases and delayed progression toward end stage chronic renal failure. Previous studies demonstrated that both red and white wine exert cardioprotective effects. In particular, wine contains Caffeic acid (CAF), an active component with known antioxidant activities. Aim of the study The aim of the present study was to investigate the protective effect of low doses of CAF on oxidative stress-induced endothelial injury. Results CAF increased basal as well as acetylcholine—induced NO release by a mechanism independent from eNOS expression and phosphorylation. In addition, low doses of CAF (100 nM and 1 μM) increased proliferation and angiogenesis and inhibited leukocyte adhesion and endothelial cell apoptosis induced by hypoxia or by the uremic toxins ADMA, p-cresyl sulfate and indoxyl sulfate. The biological effects exerted by CAF on endothelial cells may be at least in part ascribed to modulation of NO release and by decreased ROS production. In an experimental model of kidney ischemia-reperfusion injury in mice, CAF significantly decreased tubular cell apoptosis, intraluminal cast deposition and leukocyte infiltration. Conclusion The results of the present study suggest that CAF, at very low dosages similar to those observed after moderate white wine consumption, may exert a protective effect on endothelial cell function by modulating NO release independently from eNOS expression and phosphorylation. CAF-induced NO modulation may limit cardiovascular and kidney disease progression associated with oxidative stress-mediated endothelial injury.

The present review discusses the acquisitions obtained to date on the subject of wine consumption, health and cardiovascular protection. We distinguished the cardiovascular effects related to the consumption of wine and other alcoholic beverages focusing on non-alcoholic wine fraction: polyphenols and especially resveratrol. In the second part of the review we have addressed the issue of resveratrol bioavailability and the importance of wine matrix and phytocomplex highlighting the biological effects that can be obtained with nutraceuticals and resveratrol pills compared to the daily consumption of a glass of red wine.

Background: Mediterranean-style diet has been considered for its important beneficial effects on the progression of CV disease. Wine is an important component of the Mediterranean diet, and moderate wine drinkers have lower mortality rates than nondrinkers and heavy drinkers in epidemiologic studies. The beneficial effects of red wine are thought to be dependent on the polyphenol compounds such as resveratrol that exhibit potent antioxidant activity. However, white wine, although lacking polyphenols, contains simple phenols, such as tyrosol (Tyr) and hydroxytyrosol (OH-Tyr), characteristic also of extra-virgin olive oil, which may share similar antioxidant and inflammatory properties. Patients and Methods: The effect of white wine and extra-virgin olive oil on inflammatory markers was evaluated in 10 healthy volunteers and in 10 patients with CKD (chronic kidney disease) K-DOQI stage III-IV in a prospective, single blind, randomized, cross-over trial. After two weeks of wash-out from alcoholic beverages, subjects were randomized to a cross-over design A-B or B-A of a 2-week treatment with white wine (4 ml/kg body weight, 0.48 g/kg of alcohol 12%, corresponding to 2-3 glasses/daily) and extra-virgin olive oil (treatment A) or extra-virgin olive oil alone (treatment B). The two study periods were separated by a two-week wash-out period. At baseline and at the end of each treatment, plasma levels of inflammatory markers C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and interleukin-8 (IL-8) concentration were determined. Urinary levels of Tyr, OH-Tyr, and their metabolites were measured at the same time. Results: During combined consumption of white wine and extra-virgin olive oil (treatment A), plasma levels of CRP and IL-6 decreased from 4.1 ± 1.8 to 2.4 ± 1.9 mg/l (p < 0.05) and from 5.3 ± 3.2 to 3.4 ± 2.3 mg/l (p < 0.05) in CKD patients. CRP decreased from 2.6 ± 1.2 to 1.9 ± 0.9 mg/l (p < 0.05), and IL-6 decreased from 2.2 ± 1.8 to 1.7 ± 1.3 mg/l (p = ns) in healthy volunteers. No significant variation versus baseline was observed during treatment B. A significant increase in urinary Tyr and OH-Tyr was observed during treatment A (white wine and extra-virgin olive oil). Conclusions: Plasma markers of chronic inflammation were significantly reduced in CKD patients during the combined consumption of white wine and olive oil, suggesting a possible anti-inflammatory effect of this nutritional intervention.

Plants have been useful sources of new biologically active compounds. However, traditional ethno-medical approaches may draw attention to one or other clinical claim, but only specific scientific investigation can validate their effects. The aim of this study was to examine whether an extract of Melilotus officinalis leaves interferes with reactive oxygen/nitrogen species (ROS/RNS) during the course of human neutrophil respiratory bursts, and to establish the lowest concentration at which it still has antioxidant activity by means of luminol amplified chemiluminescence (LACL). We also studied its ability to counteract lipid peroxidation (LPO) in human cells. Before investigating its antioxidant effects on human cells, we analysed its scavenging activity against ABTS●+, hydroxyl radical, superoxide anion, and Fremy’s salt (the last three by means of electron paramagnetic resonance [EPR] spectrometry). The extract of M. officinalis exerted its anti-ROS/RNS activity in a concentration-dependent manner, with significant effects being observed for even very low concentration: 20 μg/ml without L-arginine (L-Arg) and 10 μg/ml when L-Arg was added to the formyl-methionyl-leucyl-phenylalanine (fMLP) test. LPO assay confirmed these results, which were paralleled by the EPR study. These findings are interesting for improving the antioxidant network and restoring redox balance in human cells, and extend the possibility of using plant-derived molecules to antagonise the oxidative stress generated in living organisms. Key words: Melilotus officinalis extract, antioxidant activity, human neutrophils, respiratory bursts, chemiluminescence, lipoperoxidation, electron paramagnetic resonance.

ADVERTISEMENT RETURN TO ISSUEPREVAddition/CorrectionNEXTORIGINAL ARTICLEThis notice is a correctionRetraction: Does White Wine Qualify for French Paradox? Comparison of the Cardioprotective Effects of Red and White Wines and Their Constituents: Resveratrol, Tyrosol, and HydroxytyrosolJocelyn I. Dudley, Istvan Lekli, Subhendu Mukherjee, Manika Das, Alberto A. A. Bertelli, and Dipak K. Das*Cite this: J. Agric. Food Chem. 2012, 60, 10, 2767Publication Date (Web):March 14, 2012Publication History Published online14 March 2012Published inissue 14 March 2012https://pubs.acs.org/doi/10.1021/jf3008597https://doi.org/10.1021/jf3008597correctionACS PublicationsCopyright © 2012 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views1870Altmetric-Citations4LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail PDF (114 KB) Get e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts

The cardioprotective and anti-aging effects of red wine phenols, especially resveratrol (RSV), are well known. One of the most interesting biological properties of RSV and other naturally occurring phenols is the regulation of the expression and activity of SIRT1 (silent mating type information regulation 2 homolog). In view of the role of SIRT1 in acute and chronic renal diseases, we decided to study the effects of RSV-poor red wines on the expression of SIRT1 and HIF-2α (hypoxia-inducible factor 2α) to be compared with a nanomolar concentration of RSV or malvidin in proximal tubular cells of human kidneys (PTEC). Survival signaling systems activation (extracellular signal-regulated kinases, ERK and AMP-activated protein kinase, AMPK) was also investigated in PTEC incubated with wines. PTEC cells were incubated in the presence of RSV-poor wines diluted 1:1,000 for 30′, 90′, 120′ and 24 h. Expression of SIRT1 and HIF-2α, and activation of ERK and AMPK were analyzed by Western Blot. The data obtained show that wine modulates the expression of anti-aging molecular systems even when RSV is present in very small amounts.

A single dose of resveratrol (25 μg/10μl) was injected directly into the right lateral cerebral ventricle (icv) of Wistar rats via an implanted cannula in order to study the analgesic properties of the compound. A control group of rats received 10 μl NaCl 0.9%. The lengthening of the time to reaction to painful stimuli was assessed in the radiant heat tail-flick latency time test. In this study, the response to painful stimuli of the animals treated with resveratrol had a bimodal profile with hypoalgesia or hyperalgesia. In the selected experimental conditions, resveratrol had a definite analgesic effect; the increase in time to reaction ranged from 100-120% (8 rats) to 600-700% (9 rats). In this experiment resveratrol exerts evident central antalgic effects in the majority of rats, which are related to the individual level of excitation and vigilance at baseline. Antinociceptive induced by resveratrol icv injection was maximal at 4-10 min and lasted no longer than 15 min. The effect of resveratrol to produce analgesia after a single icv injection may be interesting for preventing chronic pain.

Calendula officinalis of family Asteraceae, also known as marigold, has been widely used from time immemorial in Indian and Arabic cultures as an anti-inflammatory agent to treat minor skin wound and infections, burns, bee stings, sunburn and cancer. At a relatively high dose, calendula can lower blood pressure and cholesterol. Since inflammatory responses are behind many cardiac diseases, we sought to evaluate if calendula could be cardioprotective against ischemic heart disease Two groups of hearts were used: the treated rat hearts were perfused with calendula solution at 50 mM in KHB buffer (in mM: sodium chloride 118, potassium chloride 4.7, calcium chloride 1.7, sodium bicarbonate 25, potassium biphosphate 0.36, magnesium sulfate 1.2, and glucose 10) for 15 min prior to subjecting the heart to ischemia, while the control group was perfused with the buffer only. Calendula achieved cardioprotection by stimulating left ventricular developed pressure and aortic flow as well as by reducing myocardial infarct size and cardiomyocyte apoptosis. Cardioprotection appears to be achieved by changing ischemia reperfusion-mediated death signal into a survival signal by modulating antioxidant and anti-inflammatory pathways as evidenced by the activation of Akt and Bcl2 and depression of TNFα. The results further strengthen the concept of using natural products in degeneration diseases like ischemic heart disease.

A study was undertaken to determine the cardioprotective effects of parrodienes prepared from the feather pigments of parrots (Ara macao). Adult male Sprague-Dawley rats were divided into three experimental groups and perfused with KHB buffer with or without treatment of 2,4,6-octatrienal (1) (50 mM) or its potassium salt (2) (50 mM). All hearts were then subjected to 30 min ischemia followed by a 2 h reperfusion. Ischemia/reperfusion resulted in a significant amount of tissue injury, cardiomyocyte apoptosis, and depression in hemodynamic functions. Parrodiene treatment prevented the development of myocardial injury after ischemia/reperfusion. Western blot analysis indicated that 1 and 2 reduced the oxidative stress, induced the expression of Bcl-2, and caused increased phosphorylation of Akt. These agents also reduced myocardial ischemic reperfusion injury presumably by reducing oxidative stress and activating the survival signal through the Akt-Bcl-2 pathway.

Epidemiological and experimental studies have revealed that a mild to moderate drinking of wine, particularly red wine, attenuates the cardiovascular, cerebrovascular, and peripheral vascular risk. However, the experimental basis for such health benefits is not fully understood. The cardioprotective effect of wine has been attributed to both components of wine: the alcoholic portion and, more importantly, the alcohol-free portion containing antioxidants. Wines are manufactured from grapes, which also contain a large variety of antioxidants, including resveratrol, catechin, epicatechin, and proanthocyanidins. Resveratrol is mainly found in the grape skin, whereas proanthocyanidins are found only in the seeds. Recent studies have demonstrated that resveratrol and proanthocyanidin are the major compounds present in grapes and wines responsible for cardioprotection. The purpose of this review is to provide evidence that grapes, wines, and resveratrol are equally important in reducing the risk of morbidity and mortality due to cardiovascular complications. Both wines and grapes can attenuate cardiac diseases such as atherosclerosis and ischemic heart disease. Recently, wine was also found to increase life span by inducing longevity genes. It appears that resveratrol and proanthocyanidins, especially resveratrol, present in grapes and wines play a crucial role in cardioprotective abilities of grapes and wines.

There is growing interest in natural chemical compounds from aromatic, spicy, medicinal and other plants with antioxidant properties in order to find new sources of compounds inactivating free radicals generated by metabolic pathways within body tissue and cells, mainly polymorphonuclear leukocytes (PMNs) whose overregulated recruitment and activation generate a large amount of reactive oxygen species (ROS) and reactive nitrogen species (RNS), leading to an imbalance of redox homeostasis and oxidative stress. The aim of this study was to examine whether a propylene glycol extract of Calendula officinalis interferes with ROS and RNS during the PMN respiratory bursts, and to establish the lowest concentration at which it still exerts antioxidant activity by means of luminol-amplified chemiluminescence. Electron paramagnetic resonance (EPR) spectroscopy was also used in order to confirm the activity of the C. officinalis extract. The C. officinalis extract exerted its anti-ROS and anti-RNS activity in a concentration-dependent manner, with significant effects being observed at even very low concentrations: 0.20 microg/ml without L-arginine, 0.10 microg/ml when L-arginine was added to the test with phorbol 12-myristate 13-acetate and 0.05 microg/ml when it was added to the test with N-formyl-methionyl-leucyl-phenylalanine. The EPR study confirmed these findings, 0.20 microg/ml being the lowest concentration of C. officinalis extract that significantly reduced 2,2-diphenyl-1-picrylhydrazyl. These findings are interesting for improving the antioxidant network and restoring the redox balance in human cells with plant-derived molecules as well as extending the possibility of antagonizing the oxidative stress generated in living organisms when the balance is in favor of free radicals as a result of the depletion of cell antioxidants.