Constituent Of Red Wine Research Articles

Grape-derived pectic polysaccharides alter the tannin and pigment composition of Cabernet Sauvignon red wines

Tannins, anthocyanins, and polymeric pigments are essential phenolic constituents of red wine because they provide color, color stability, and mouthfeel properties like astringency. The behavior of these compounds is significantly affected by pectic polysaccharides, whereby the extent of their influence on red wine quality depends on their structural features and their interactions with the polyphenols. In the present study, the composition of the pectic polysaccharides of commercially available Cabernet Sauvignon wines and their impact on anthocyanin, tannin, and polymeric pigment analyses was characterized. This was accomplished by preparation of polysaccharide deprived wines and comparison of the polyphenolic composition of both, the wines and their corresponding polysaccharide-free counterparts. The results show that the cell wall fragments enhance the spectral absorbance of anthocyanins by facilitating anthocyanin self-association, leading to a co-pigmentation-like effect. Low molecular weight pectins like rhamnogalacturonan II and polygalacturonic acids with a low degree of esterification are assumed to form soluble complexes with anthocyanins and also prevent protein precipitation of tannins, which was reduced by 6–13%. High molecular weight pectins with a high degree of esterification lead to the increased precipitability of pigments and tannins by a factor of 1.3 to 32.4 and 1.1 to 1.9, respectively, seemingly impairing the incorporation of anthocyanins in tannins to form precipitable polymeric pigments that are responsible for the longevity of red wine color. The increased precipitability of the pigments due to the interactions with the polysaccharides may indicate the formation of pigmented yet non-covalent aggregates that show comparable properties to the covalently formed precipitable pigments. The formation of those non-covalent structures may affect red wine color stability and astringency.

Chemical Composition and Polyphenolic Compounds of Red Wines: Their Antioxidant Activities and Effects on Human Health—A Review

Red wine, an alcoholic beverage is composed of a spectrum of complex compounds such as water, alcohol, glycerol, organic acid, carbohydrates, polyphenols, and minerals as well as volatile compounds. Major factors that affect the levels of phenolic compounds in red wines are the variety of grapes and the storage of the wines. Among the constituents of red wine, phenolic compounds play a crucial role in attributes including color and mouthfeel and confer beneficial properties on health. Most importantly, phenolic compounds such as flavanols, flavonols, flavanones, flavones, tannins, anthocyanins, hydroxycinnamic acids, hydroxybenzoic acids, and resveratrol can prevent the development of cardiovascular diseases, cancers, diabetes, inflammation, and some other chronic diseases.

Wine tannins: Where are they coming from? A method to access the importance of berry part on wine tannins content

Phenolic compounds are important constituents of red wine involved in its sensory properties. Although wine tannins can come from microbial and oak sources, the main sources of polyphenol remains grape skins and seeds. In order to better understand the grape seed and skin tannins contribution to the final wine tannins content, an original approach of winemaking has been set up. Our protocol explains a simple method to determine the percentage of skin and seed tannins extracted in wine all along the winemaking. The advantages of this method are presented below:•This method allows us to describe tannins extraction kinetics in wine according to the berry part (skins and seeds).•Additionally, our protocol allows to specifically determine the percentage of tannins extraction according to the winemaking stages (alcoholic fermentation and post-fermentative maceration) and the berry part (skins and seeds).•To sum up, this method serves to enhance the comprehension of tannins extraction process in wine according to the berry part.

Bovine serum albumin-based nanoparticles containing the flavonoid rutin produced by nano spray drying

Rutin is a flavonoid compound obtained from different vegetables and fruits; specifically, it is found in the seeds of buckwheat and in fruit peels, particularly citrus. It is also an important constituent of red wine. Rutin exhibits various biological properties including antiviral, vasoprotective, anti-inflammatory, and anticarcinogenic activities. However, its antioxidant activity is the most well studied. Despite the potential for in vitro applications, rutin presents low oral bioavailability that affects its biological activities. Nanoparticles composed of polymers, protein, or lipids are of great importance in the pharmaceutical and nutraceutical areas due to their physicochemical properties, which improve the pharmacokinetics of the drug which is loaded within. This study presents the production of bovine serum albumin (BSA) nanoparticles containing rutin by nano spray drying. Nanoparticles were characterized in terms of mean particle size, size distribution, morphology, zeta potential, and drug content; as well as their antioxidant activity. The optimized spray-drying conditions produced spherical particles with a mean size of 316 nm, zeta potential of −32 mV, and encapsulation efficiency around 32%. Moreover, when antioxidant activity toward the ABTS+ radical was assayed, nanoencapsulation increased the IC50 of rutin by 2-fold. The nano spray-drying process proved to be suitable for the production of rutin-loaded BSA nanoparticles with potential antioxidant activity.

Mechanism of resveratrol-induced relaxation of the guinea pig fundus

BackgroundResveratrol is a polyphenolic compound that can be isolated from plants and also is a constituent of red wine. Resveratrol induces relaxation of vascular smooth muscle and may prevent cardiovascular diseases. PurposeImpaired gastric accommodation plays an important role in functional dyspepsia and fundic relaxation and is a therapeutic target of functional dyspepsia. Although drugs for fundic relaxation have been developed, these types of drugs are still rare. The purpose of this study was to investigate the relaxant effects of resveratrol in the guinea pig fundus. Study DesignWe studied the relaxant effects of resveratrol in the guinea pig fundus. In addition, we investigated the mechanism of resveratrol-induced relaxation on the guinea pig fundus by using tetraethylammonium (a non-selective potassium channel blocker), apamine (a selective inhibitor of the small conductance calcium-activated potassium channel), iberiotoxin (an inhibitor of large conductance calcium-activated potassium channels), glibenclamide (an ATP-sensitive potassium channel blocker), KT 5720 (a cAMP-dependent protein kinase A inhibitor), KT 5823 (a cGMP-dependent protein kinase G inhibitor), NG-nitro-L-arginine (a competitive inhibitor of nitric oxide synthase), tetrodotoxin (a selective neuronal Na+ channel blocker), ω-conotoxin GVIA (a selective neuronal Ca2+ channel blocker) and G-15 (a G-protein coupled estrogen receptor antagonist). ResultsThe results of this study showed that resveratrol has potent and dose-dependent relaxant effects on the guinea pig fundic muscle. In addition, the results showed that resveratrol-induced relaxation of the guinea pig fundus occurs through nitric oxide and ATP-sensitive potassium channels. ConclusionThis study provides the first evidence concerning the relaxant effects of resveratrol in the guinea pig fundic muscle strips. Furthermore, resveratrol may be a potential drug to relieve gastrointestinal dyspepsia.

Combinatorial Preconditioning of Rat Brain Cultures with Subprotective Ethanol and Resveratrol Concentrations Promotes Synergistic Neuroprotection.

Preconditioning brain cultures with moderate concentrations of ethanol (EtOH) or trans-resveratrol (RES), key red wine constituents, can prevent amyloid-β (Aβ) neurotoxicity. Past studies have indicated that moderate EtOH activates synaptic N-methyl-D-aspartate receptors (NMDAR) that, in part, signal via protein kinase C (PKC) to increase protective antioxidant proteins such as peroxiredoxin-2 (Prx2). RES preconditioning also is reported to involve NMDAR and PKC. However, although moderate, the EtOH and RES concentrations used have been noticeably above circulating levels from two glasses of wine, a daily intake linked to reduced risk of cognitive decline among older social drinkers. Given their mechanistic parallels, we speculated that subprotective EtOH and RES concentrations in a combinatorial preconditioning paradigm might elicit synergistic neuroprotection. To examine this notion, rat cerebellar cultures were pretreated with 10mM EtOH (circulating concentration after ~ 2 drinks), 5μM RES, EtOH + RES combinatorially, or media alone (controls). After 3days, media were removed, and fresh media aliquots containing Aβ25-35 (25μM) were added. Assessing apoptosis 24h later with Hoescht 33342, neurodegeneration did not differ from controls in cultures separately preconditioned with 10mM EtOH or 5μM RES. However, apoptosis was prevented in combinatorially preconditioned cultures. Also, immunoblotting revealed elevated Prx2 levels due to combinatorial pretreatment that correlated with subsequent neuroprotection, whereas Prx2 was unchanged in separately pretreated cultures. Although the protective mechanisms require clarification, synergistically upregulated NMDAR-PKC-Prx2 (and other antioxidant proteins) is a reasonable component. These findings imply that EtOH + RES antioxidant synergy could be involved in neurobenefits attributed to low-moderate wine consumption.

Antioxidant and Antihypertensive Effects of a Chemically Defined Fraction of Syrah Red Wine on Spontaneously Hypertensive Rats.

A particularly phenolic-rich fraction extracted from red wine from the São Francisco valley (Northeastern Brazil) was chemically characterized and its hypotensive and antioxidant effects on spontaneously hypertensive rats were studied both in vitro and in vivo. The liquid-liquid pH dependent fractionation scheme afforded a fraction with high content of bioactive phenolics such as flavonols, flavonol glycosides, phenolic acids and anthocyanins, whose identities were confirmed by liquid chromatography coupled to mass spectrometry analysis. Pretreatment of spontaneously hypertensive rats with this wine fraction at doses of 50 and 100 mg/kg by gavage for 15 days was able to decrease mean arterial pressure and heart rate as well as decrease serum lipid peroxidation. The fraction at concentrations of 0.01–1000 µg/mL induced concentration-dependent relaxation of isolated rat superior mesenteric artery rings pre-contracted with phenylephrine and this effect was not attenuated by endothelium removal. Our results demonstrate it is possible for phenolic constituents of red wine that are orally bioavailable to exert in vivo hypotensive and antioxidant effects on intact endothelial function.

Mechanism of resveratrol-induced relaxation in the human gallbladder

BackgroundResveratrol is a polyphenolic compound extracted from plants and is also a constituent of red wine. Resveratrol produces relaxation of vascular smooth muscle and may prevent cardiovascular diseases. Although resveratrol has been reported to cause relaxation of the guinea pig gallbladder, limited data are available about the effect of resveratrol on the gallbladder smooth muscle in humans. The purpose of this study was to investigate the relaxation effects of resveratrol in human gallbladder muscle strips.MethodsWe studied the relaxant effects of resveratrol in human gallbladder. In addition, we also investigated mechanism of resveratrol-induced relaxation in human gallbladder by tetraethylammonium (a non-selective potassium channels blocker), iberiotoxin (an inhibitor of large conductance calcium-activated potassium channel), glibenclamide (an ATP-sensitive potassium channel blocker), charybdotoxin (an inhibitor of large conductance calcium-activated potassium channels and slowly inactivating voltage-gated potassium channels), apamine (a selective inhibitor of the small conductance calcium-activated potassium channel), KT 5720 (a cAMP-dependent protein kinase A inhibitor), KT 5823 (a cGMP-dependent protein kinase G inhibitor), NG-Nitro-L-arginine (a competitive inhibitor of nitric oxide synthase), tetrodotoxin (a selective neuronal Na+ channel blocker), and ω-conotoxin GVIA (a selective neuronal Ca2+ channel blocker).ResultsThe present study showed that resveratrol has relaxant effects in human gallbladder muscle strips. In addition, we found that resveratrol-induced relaxation in human gallbladder is associated with nitric oxide, ATP-sensitive potassium channel, and large conductance calcium-activated potassium channel pathways.ConclusionsThis study provides the first evidence concerning the relaxant effects of resveratrol in human gallbladder muscle strips. Furthermore, these results demonstrate that resveratrol is a potential new drug or health supplement in the treatment of biliary colic.

Adsorption of Wine Constituents on Functionalized Surfaces.

The adsorption of macromolecules on solid surfaces is of great importance in the field of nanotechnology, biomaterials, biotechnological, and food processes. In the field of oenology adsorption of wine macromolecules such as polyphenols, polysaccharides, and proteins is much less desirable on membrane materials because of fouling and reduced filtering performance. On the other hand, adsorption of these molecules on processing aids is very beneficial for achieving wine clarity and stability. In this article, the effect of surface chemical functionalities on the adsorption of white, rosé, and red wine constituents was evaluated. Allylamine, acrylic acid, and ethanol were selected as precursors for plasma polymerization in order to generate coatings rich in amine, carboxyl, and hydroxyl chemical groups, respectively. The surface chemical functionalities were characterized by X-ray photoelectron spectroscopy (XPS) and the ability of different surface chemical functionalities to adsorb wine constituents were characterized by quartz crystal microbalance with dissipation (QCM-D) and atomic force microscopy (AFM). The results demonstrated that the amine and carboxyl modified surfaces encourage adsorption of constituents from white wine. The hydroxyl modified surfaces have the ability to preferentially adsorb rosé wine constituents, whereas red wine adsorbed to the highest extent on acrylic acid surface.

Surface modification influencing adsorption of red wine constituents: The role of functional groups

The adsorption of wine constituents at solid surfaces is important in applications such as filtration and membrane fouling, binding to tanks and fittings and interactions with processing aids such as bentonite. The interaction of wine constituents with surfaces is mediated through adsorbed wine components, where the type of constituents, amount, orientation, and conformation are of consequence for the surface response. This study examines the effect of surface chemical functionalities on the adsorption of red wine constituents. Plasma-polymerized films rich in amine, carboxyl, hydroxyl, formyl and methyl functional groups were generated on solid substrates whereas, glycidyltrimethylammonium chloride was covalently attached to allylamine plasma-polymer modified surface and poly(sodium styrenesulfonate) was electrostatically adsorbed to an amine plasma-polymerized surface. The surface chemical functionalities were characterized by X-ray photoelectron spectroscopy. The ability of different substrates to adsorb red wine constituents was evaluated by quartz crystal microbalance and atomic force microscopy. The results showed that substrates modified with −SO3H and –COOH groups can adsorb more of the wine nitrogen-containing compounds whereas −NH2 and −NR3 groups encourage carbon-containing compounds adsorption. Red wine constituents after filtration were adsorbed in higher extend on −NR3 and –CHO surfaces. The –OH modified surfaces had the lowest ability to absorb wine components.

Interaction of Resveratrol with Lipid Membranes

Background: Resveratrol is a phytoalexin synthesized by plants. It has antioxidant properties and is a popular nutritional supplement. Beneficial properties of resveratrol, such as, anticancer and anti-inflammatory properties have been reported. Resveratrol is a constituent of red wine and found in the skin of red grapes. In order to understand the interaction between resveratrol and biological membranes, we evaluated the effect of resveratrol on model lipid membranes using differential scanning calorimetry (DSC) and computational studies. Methods: Phospholipids such as, Dilauroylphosphatidylcholine (DLPC), Dimyristoyphosphatidylcholine (DMPC), Dipalmitoylphosphatidyl choline (DPPC), Distearoylphosphatidylcholine (DSPC), and 1-palmitoyl-2-oleyl phosphatidylcholine (POPC) were purchased from Avanti Polar Lipids (Alabaster, Alabama). Each phospholipid was mixed with resveratrol at different molar ratios, phospholipid: resveratrol, 10:1, 10:3 and 10:5. Computational simulations were also performed to evaluate the interactions of DSPC and resveratrol. Results: Resveratrol abolishes only the transition of the DLPC, which is the shortest phospholipid of those tested. It reduces the transition temperature for all the other phospholipids even at the lowest ratio tested, phospholipid: resveratrol, 10:1. Resveratrol reduces the transition temperature of DSPC from 55 °C to 51 °C. Furthermore, using DSC, we also observed another transition, a sharp exothermic peak above 275 °C in the interaction of resveratrol with DSPC. We performed computational simulations of the DSPC membrane at different temperatures with and without resveratrol. The simulation indicates that resveratrol affects the transition temperature of the DSPC, which is in agreement with our DSC data. In conclusion, our data indicate that resveratrol abolishes the transition of DLPC and acts as a plasticizer for phospholipids with longer fatty acyl chains.

Phytoestrogens modulate hepcidin expression by Nrf2: Implications for dietary control of iron absorption

Hepcidin is a liver-derived antimicrobial peptide that regulates iron absorption and is also an integral part of the acute phase response. In a previous report, we found evidence that this peptide could also be induced by toxic heavy metals and xenobiotics, thus broadening its teleological role as a defensin. However it remained unclear how its sensing of disparate biotic and abiotic stressors might be integrated at the transcriptional level. We hypothesized that its function in cytoprotection may be regulated by NFE2-related factor 2 (Nrf2), the master transcriptional controller of cellular stress defenses. In this report, we show that hepcidin regulation is inextricably linked to the acute stress response through Nrf2 signaling. Nrf2 regulates hepcidin expression from a prototypical antioxidant response element in its promoter, and by synergizing with other basic leucine-zipper transcription factors. We also show that polyphenolic small molecules or phytoestrogens commonly found in fruits and vegetables including the red wine constituent resveratrol can induce hepcidin expression in vitro and post-prandially, with concomitant reductions in circulating iron levels and transferrin saturation by one such polyphenol quercetin. Furthermore, these molecules derepress hepcidin promoter activity when its transcription by Nrf2 is repressed by Keap1. Taken together, the data show that hepcidin is a prototypical antioxidant response or cytoprotective gene within the Nrf2 transcriptional circuitry. The ability of phytoestrogens to modulate hepcidin expression in vivo suggests a novel mechanism by which diet may impact iron homeostasis.

Resveratrol: A Sirtuin Activator and The Fountain of Youth

BACKGROUND: An organism’s lifespan is inevitably accompanied by the aging process, which involves functional decline, a steady increase of a plethora of chronic diseases, and ultimately death. Thus, it has been an ongoing dream of mankind to improve healthspan and extend life.CONTENT: There are only a few proposed aging interventions: caloric restriction, exercise, and the use of low-molecular-weight compounds, including spermidine, metformin, resveratrol, and rapamycin. Resveratrol, a constituent of red wine, has long been suspected to have cardioprotective effects. Interest in this compound has been renewed in recent years, first from its identification as a chemopreventive agent for skin cancer, and subsequently from reports that it activates sirtuin deacetylases and extends the lifespans of lower organisms. Resveratrol have been shown to prevent and reduce the severity of age-related diseases such as atherosclerosis, stroke, myocardial infarct, diabetes, neurodegenerative diseases, osteoarthritis, tumors and metabolic syndrome, along with their ability to extend lifespan.SUMMARY: The purpose of aging research is the identification of interventions that may avoid or ameliorate the ravages of time. In other words, the quest is for healthy aging, where improved longevity is coupled to a corresponding healthspan extension. It is only by extending the healthy human lifespan that we will truly meet the premise of the Roman poet Cicero: “No one is so old as to think that he may not live a year.”KEYWORDS: aging, caloric restriction, mimetic, healthspan, sirtuin activator

Resveratrol: Biological Activities and Therapeutic Potential

Resveratrol is a polyphenolic flavonoid initially identified as a phytoalexin and as a major constituent of red wine. However interest in this molecule initially developed as a cardioprotective agent and in due course of time therapeutic actions came into limelight. This article explores the different therapeutic activities of Resveratrol and highlights their possible mode of action responsible for its therapeutic action. It becomes evident from this article that Resveratrol has a pharmacological agent that has widespread targets and therefore due emphasis on specific biological action need to be addressed using medicinal chemistry and quantitative structure activity relationships in developing new congeners of Resveratrol to be exploited as drugs.

Resveratrol promotes degradation of the human bile acid transporter ASBT (SLC10A2)

The sodium/bile acid co-transporter ASBT [apical sodium-dependent bile acid transporter; SLC10A2 (solute carrier family 10 member 2)] plays a key role in the enterohepatic recycling of the bile acids and indirectly contributes to cholesterol homoeostasis. ASBT inhibitors reportedly lower plasma triglyceride levels and increase HDL (high-density lipoprotein) cholesterol levels. RSV (resveratrol), a major constituent of red wine, is known to lower LDL (low-density lipoprotein) cholesterol levels, but its mechanism of action is still unclear. In the present study, we investigated the possible involvement of ASBT in RSV-mediated cholesterol-lowering effects. We demonstrate that RSV inhibits ASBT protein expression and function via a SIRT1 (sirtuin 1)-independent mechanism. The effect was specific to ASBT since other transporters involved in cholesterol homoeostasis, NTCP (SLC10A1), OSTα (SLC51A) and ABCG1 (ATP-binding cassette G1), remained unaffected. ASBT inhibition by RSV was reversed by proteasome inhibitors (MG-132 and lactacystin) and the ubiquitin inhibitor LDN57444, suggesting involvement of the ubiquitin-proteasome pathway. Immunoprecipitation revealed high levels of ubiquitinated ASBT after RSV treatment. Phosphorylation at Ser335 and Thr339 was shown previously to play a role in proteosomal degradation of rat ASBT. However, mutation at corresponding residues in rat ASBT revealed that phosphorylation does not contribute to RSV-mediated degradation of ASBT. Combined, our data indicate that RSV promotes ASBT degradation via the ubiquitin-proteasome pathway without requiring phosphorylation. We conclude that regulation of ASBT expression by RSV may have clinical relevance with regard to the observed cholesterol-lowering effects of RSV.

Resveratrol protects against atherosclerosis, but does not add to the antiatherogenic effect of atorvastatin, in APOE*3-Leiden.CETP mice

Resveratrol is a major constituent of traditional Asian medicinal herbs and red wine and is suggested to be a potential antiatherosclerotic drug due to its proposed hypolipidemic, anti-inflammatory and antioxidative properties. The aim of this study was to evaluate whether resveratrol protects against atherosclerosis development in APOE*3-Leiden.CETP (E3L.CETP) mice and adds to the antiatherogenic effect of mild statin treatment, currently the most widely used antiatherogenic therapy. E3L.CETP mice were fed a cholesterol-rich diet without (control) or with resveratrol (0.01% w/w), atorvastatin (0.0027% w/w) or both for 14 weeks. During the study plasma lipid, inflammatory and oxidative stress parameters were determined. Resveratrol reduced atherosclerotic lesion area (−52%) in the aortic root, comparable to atorvastatin (−40%) and the combination of both drugs (−47%). The collagen/macrophage ratio in the atherosclerotic lesion, a marker of plaque stability, was increased by resveratrol (+108%), atorvastatin (+124%) and the combination (+154%). Resveratrol decreased plasma cholesterol levels (−19%) comparable to atorvastatin (−19%) and the combination (−22%), which was completely confined to (very)low-density lipoprotein cholesterol levels in all groups. Post hoc analyses showed that the antiatherogenic effect of atorvastatin could be explained by cholesterol lowering, while the antiatherosclerotic effect of resveratrol could be attributed to factors additional to cholesterol lowering. Markers of inflammation and oxidative stress were not different, but resveratrol improved macrophage function. We conclude that resveratrol potently reduces atherosclerosis development and induces a more stable lesion phenotype in E3L.CETP mice. However, under the experimental conditions tested, resveratrol does not add to the antiatherogenic effect of atorvastatin.

Modulation of microRNA 20b with resveratrol and longevinex is linked with their potent anti‐angiogenic action in the ischaemic myocardium and synergestic effects of resveratrol and γ‐tocotrienol

Resveratrol, a constituent of red wine, and γ-tocotrienol, a constituent of palm oil are important for cardioprotection. Although microRNAs are known regulators for genes involved in cardiac remodelling, the regulatory pathway involving microRNA has not been studied so far. We explored the cardioprotection by resveratrol, longevinex and γ−tocotrienol in ischaemia/reperfusion(I/R) model of rat and determined miRNA profile from isolated RNA. Systemic analyses of miRNA array and theirs targets were determined using a number of computational approaches. Resveratrol and γ-tocotrienol, either alone or in combination, modulated the expression pattern of miRNAs close to the control level based on PCA analyses. Differential expression was observed in over 75 miRNAs, some of them, such as miR-21 and miR-20b (anti-angiogenic) were previously implicated in cardiac remodelling. The target genes for the highest differentially expressed miRNA include genes of various molecular functions such as TGFβ1–Smad3 signalling pathway, inflammation and their transcription factors, which may play key role in reducing I/R injury. Administration of antagomiR-20 attenuated I/R induced vascular endothelial growth factor and HIF1α level. All the interventions treated for 3 weeks lead to significant cardioprotection against ischaemia/reperfusion injury. A unique signature of miRNA profile is observed in control heart pretreated with resveratrol or γ-tocotrienol. We have determined specific group of miRNA in heart that have altered during IR injuries. Most of those altered microRNA expressions modulated close to their basal level in resveratrol or longevinex treated I/R rat. Interestingly, resveratrol and γ-tocotrienol resulted in synergestic action.

Red Wine and Cardiovascular Health

There is strong epidemiological evidence that light-to-moderate consumption of alcoholic drinks, but neither zero nor more than moderate intake, reduces mortality from all causes and also diminishes cardiovascular risk.1 The lowest risk for coronary heart disease mortality is seen with 1 to 2 drinks (12.5–25g alcohol) per day. Article, see p 1065 Hypertension is a major risk factor for cardiovascular disease, and there is a clear inverse relationship between light-to-moderate alcohol intake and blood pressure. Thus, the reduced cardiovascular risk associated with moderate consumption of alcoholic drinks may be due, in part, to a reduction in blood pressure. The greatest blood pressure benefit seems to be obtained with 1 drink per day for women and with 2 drinks per day for men.2 In most published studies, red wine has been used as the alcoholic test beverage. Red wine produces concentration-dependent vasodilator effects in subcutaneous small resistance arteries obtained from patients with essential hypertension.3 In addition, red wine and dealcoholized red wine increase flow-mediated vasodilation of the brachial artery in healthy subjects.4,5 Intake of red wine also counteracts endothelial dysfunction produced by high-fat diet in human volunteers,6 and red wine increases flow-mediated vasodilation and decreases blood pressure in adult cigarette smokers.7,8 With red wine, both the alcoholic and the polyphenolic components seem to contribute to its beneficial effects.9 The alcoholic component is known to increase high-density lipoprotein cholesterol and to decrease fibrinogen concentrations.10 The polyphenols present in red wine have been shown …

Reconstituted High Density Lipoprotein Bearing Apolipoprotein E3 Serves as a Nanovehicle to Transport and Target Bioflavonoids such as Resveratrol

The objective of this study is to transport resveratrol, an antioxidant and anti-inflammatory bioflavonoid, in the plasma to targeted sites. Resveratrol is a phytoalexin polyphenol that is found in natural products such as grape skins, cocoa, and is a constituent of red wine. It appears to be a potent factor as an anti-cancer and atheroprotective agent. The “French Paradox” (French suffering a relatively lower incidence of coronary heart disease compared to other western societies) has been attributed to the benefits of resveratrol (as a result of higher consumption of red wine by the French). However, it is difficult to achieve effective concentrations of resveratrol in plasma via the oral tract from natural resveratrol-rich products. Its low aqueous solubility appears to limit the use of resveratrol as a nutraceutical agent. We propose to employ apolipoprotein E3 (apoE3)-containing reconstituted high density lipoproteins (rHDL) for transportation and targeted delivery of resveratrol. rHDL are water soluble lipoprotein complexes composed of a bilayer of phospholipids surrounded by apoE3, which bears high affinity binding sites for the cell surface localized low density lipoprotein receptor (LDLr). The phospholipid microenvironment of rHDL is expected to provide a centrally located lipid milieu into which resveratrol may be sequestered, and shielded from modification and/or degradation. Our data indicates that resveratrol has effectively partitioned into the hydrophobic milieu of the phospholipid bilayer of rHDL without significant alteration to the conformation of apoE3. Importantly, the presence of resveratrol did not alter the LDLr binding ability of apoE3. These results indicate that rHDL bearing the apoE3 LDLr binding domain can serve as an effective “nanovehicle” to transport and potentially deliver resveratrol to targeted sites across the cell membrane.Funded by CSUPERB and TRDRP 17RT-0165.

Nutraceuticals and Mediterranean Diet

In recent years, the chemistry research of natural products has focused on the identification of biologically active secondary metabolites in plants, commonly used as vegetables in the human diet and which, in past centuries, had been used not only as food or spices but also in traditional medicinal remedies. The main contribution that can be attributed to plants is the introduction for example of vitamins or minerals to the human diet. However, they contain other secondary metabolites, which are defined as nutraceuticals and which have recently been, at the center of large scientific studies. Edible plants are rich in polyphenols [1], terpenoids [2-4], flavonoids, alkaloids, sterols, pigments and unsaturated fatty acids, which play an important role in maintaining wellness. The Mediterranean diet includes a good amount of plant food (fruits, vegetables, nuts, seeds, wine, olive oil) [5], which by preventing oxidation reactions, results in a significant reduction of risk factors in coronary heart disease and in lowering cholesterol levels in blood [6]. They also result in the decrease in the risk of chronic degenerative diseases such as cancer, Alzheimer’s, Parkinson’s disease, autoimmune diseases and multiple sclerosis [7,8]. Epidemiological studies have attributed these positive effects to the presence of compounds having antioxidant activity in foods (and beverages) commonly known as polyphenols. From the chemical point of view the polyphenols are classified into two groups: flavonoids and non-flavonoids. Belonging to the flavonoids group, flavonols present themselves both in free form or as glycosides; the flavan-3-ols such as catechin, and anthocyanins such as malvidin-3-glycoside. Among the non-flavonoids there is gallic acid, the hydroxicinnamate such as p-coumaric acid, caffeic acid [9] and the caftaric acid and stilbenes such as transand cis-resveratrol. The most significant component of the polyphenols is made up of condensed tannins, also known as procyanidins. They are oligomers and polymers of catechins (catechin or epicatechin), condensed by 4-6 and 4-8 carbon-carbon bonds. Grapes contain catechins and procyanidins in the seeds and skins and are major constituents of red wine, along with resveratrol; epigallocatechin is abundant in green tea [8-10]. The interest for the antioxidant compounds derives from the observation of their role in modulating the production of free radicals. A very timely topic in research on the pathogenesis of many diseases is related to the role played by the uncontrolled formation of free radicals: the action of free radicals as mediators of tissue damage is in fact recognized in many pathophysiological processes such as inflammation, atherosclerosis, ischemia, tumors, the damage induced by ionizing radiation, aging and skin photoreaction.