SciCombinator

Discover the most talked about and latest scientific content & concepts.

Concept: Resveratrol

172

Resveratrol is a bioactive polyphenol enriched in red wine that exhibits many beneficial health effects via multiple mechanisms. However, it is unclear whether resveratrol is beneficial for the prevention of food allergy. This study investigated whether resveratrol inhibited the development of food allergy by using a mouse model of the disease.

Concepts: Human, Nutrition, Allergy, Mouse, Resveratrol, Wine, Polyphenol, French Paradox

171

Sirtuins are protein deacetylases regulating metabolism, stress responses, and aging processes, and they were suggested to mediate the lifespan extending effect of a low calorie diet. Sirtuin activation by the polyphenol resveratrol can mimic such lifespan extending effects and alleviate metabolic diseases. The mechanism of Sirtuin stimulation is unknown, hindering the development of improved activators. Here we show that resveratrol inhibits human Sirt3 and stimulates Sirt5, in addition to Sirt1, against fluorophore-labeled peptide substrates but also against peptides and proteins lacking the non-physiological fluorophore modification. We further present crystal structures of Sirt3 and Sirt5 in complex with fluorogenic substrate peptide and modulator. The compound acts as a top cover, closing the Sirtuin’s polypeptide binding pocket and influencing details of peptide binding by directly interacting with this substrate. Our results provide a mechanism for the direct activation of Sirtuins by small molecules and suggest that activators have to be tailored to a specific Sirtuin/substrate pair.

Concepts: Protein, Amino acid, Metabolism, Histone deacetylase, Antioxidant, Resveratrol, Sirtuin, Sir2

170

Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a polyphenol found in various plants, especially in the skin of red grapes. The effect of resveratrol on human health is the topic of numerous studies. In fact this molecule has shown anti-cancer, anti-inflammatory, blood-sugar-lowering ability and beneficial cardiovascular effects. However, for many polyphenol compounds of natural origin bioavailability is limited by low solubility in biological fluids, as well as by rapid metabolization in vivo. Therefore, appropriate carriers are required to obtain efficient therapeutics along with low administration doses.Liposomes are excellent candidates for drug delivery purposes, due to their biocompatibility, wide choice of physico-chemical properties and easy preparation.In this paper liposome formulations made by a saturated phosphatidyl-choline (DPPC) and cholesterol (or its positively charged derivative DC-CHOL) were chosen to optimize the loading of a rigid hydrophobic molecule such as resveratrol.Plain and resveratrol loaded liposomes were characterized for size, surface charge and structural details by complementary techniques, i.e. Dynamic Light Scattering (DLS), Zeta potential and Small Angle X-ray Scattering (SAXS). Nuclear and Electron Spin magnetic resonances (NMR and ESR, respectively) were also used to gain information at the molecular scale.The obtained results allowed to give an account of loaded liposomes in which resveratrol interacted with the bilayer, being more deeply inserted in cationic liposomes than in zwitterionic liposomes. Relevant properties such as the mean size and the presence of oligolamellar structures were influenced by the loading of RESV guest molecules.The toxicity of all these systems was tested on stabilized cell lines (mouse fibroblast NIH-3T3 and human astrocytes U373-MG), showing that cell viability was not affected by the administration of liposomial resveratrol.

Concepts: Electron, Electric charge, Molecule, Scattering, Resveratrol, Polyphenol antioxidant, Polyphenol, Dynamic light scattering

165

BACKGROUND: Resveratrol is an important stilbene that benefits human health. However, it is only distributed in a few species including grape and is very expensive. At present, grape has been an important source resveratrol. However, the details are scarce on resveratrol distribution in different Vitis species or cultivars. METHODOLOGYPRINCIPAL FINDING: The composition and content of resveratrols were investigated by HPLC for assessing genotypic variation in berry skins and leaves of 75 grape cultivars, belonging to 3 species and 7 interspecific hybrids. Trans-resveratrol, cis-piceid and trans-piceid were detected in berry skins and leaves, but cis-resveratrol was not. Resveratrol content largely varied with genetic background as well as usage. In most cultivars, total resveratrol including the above three compounds was higher in berry skins than leaves. In berry skins of most cultivars and leaves of almost all cultivars, cis-piceid was the most abundant resveratrol; trans-resveratrol and trans-piceid were minor components. Some specific cultivars were found with extremely high levels of trans-resveratrol, cis- piceid, trans-piceid or total resveratrols in berry skins or leaves. In skins and leaves, rootstock cultivars had a higher content of total resveratrols, and the cultivated European type cultivars and their hybrids with V. labrusca had relatively low totals. There were no significant correlations of the amounts of total resveratrols or any individual resveratrol between berry skins and leaves. All 75 cultivars can be divided into four groups based on the composition of resveratrols and their concentration by principal component analysis. CONCLUSION: Resveratrol content of grape berries and leaves varied largely with their genetic background and usage. Rootstock cultivars had a higher content of total resveratrols than the other germplasm. Total resveratrols were lower in leaves than berry skins in most cultivars. Cis-piceid was the most abundant resveratrol in most cultivars, and trans-res and trans-pd were minor components.

Concepts: Vitis vinifera, Resveratrol, Grape, Vitis, Vitaceae, Vitis riparia, Vitis labrusca, Muscadine

163

Flavonoids are a significant group of secondary metabolites in plants. Many of these compounds are potent antioxidants, being an important part in food products derived from the plants. The current status of research on flavonoid compounds in the fruit of Saskatoon berries (Amelanchier alnifolia Nutt.) and their health promoting effects, including recommended utilization, are reviewed. The major classes of flavonoids in the fruit are flavonols (quercetin and rutin), flavanes (proanthocyanidin compounds ranging from dimers through to heptamers and even higher polymers) and finally anthocyanins. The flavonoids represented the group of polyphenols that mostly contributed to the antioxidant activity of Saskatoon berries. High content of the flavoinoids antioxidants in the fruit is responsible for the observed anti-inflammatory, antidiadiabetic and chemo-protective effects.

Concepts: Nutrition, Antioxidant, Flavonoid, Resveratrol, Polyphenol, Flavonols, Rutin, Amelanchier alnifolia

30

Phytonutrients reportedly extend the lifespan of C. elegans, Drosophila, and mice. We tested extracts of blueberry, pomegranate, green and black tea, cinnamon, sesame, and French maritime pine bark (Pycnogenol and taxifolin), as well as curcumin, morin, and quercetin for their effects on the lifespan of mice. While many of these phytonutrients reportedly extend the lifespan of model organisms, we found no significant effect on the lifespan of male, F1 hybrid mice, even though the dosages used reportedly produce defined therapeutic endpoints in mice. The compounds were fed beginning at 12 months of age. The control and treatment groups were isocaloric with respect to one another. A 40% calorically restricted and other groups not reported here did experience lifespan extension. Body weights were unchanged relative to controls for all but two supplemented groups, indicating most supplements did not change energy absorption or utilization. Tea extracts with morin decreased weight, while quercetin, taxifolin, and Pycnogenol together increased weight. These changes may be due to altered locomotion or fatty acid biosynthesis. Published reports of murine lifespan extension using curcumin or tea components may have resulted from induced caloric restriction. Together, our results do not support the idea that phytonutrient-antioxidants and anti-inflammatories are potential longevity therapeutics, even though consumption of whole fruits and vegetables is associated with enhanced health- and lifespan.

Concepts: Nutrition, Caenorhabditis elegans, Model organism, Gerontology, Fruit, Resveratrol, Calorie restriction, Medicinal plants

29

Profound research has been done on the medicinal value of Brassica nigra (BN) seeds, and the leaves of the plant have been investigated in this study. The methanol extracts of the leaves were subjected to several in vitro studies. The antioxidant activity of methanol extract was demonstrated with a wide range of concentration, 10-500 µg mL(-1), and the antioxidant activity increased with the increase in concentration. Total phenol content was found to be 171.73 ± 5.043 gallic acid equivalents and the total flavonoid content 7.45 ± 0.0945 quercetin equivalents. Further quantification and identification of the compounds were done by HPTLC and GC-MS analyses. The predominant phenolic compounds determined by HPTLC were gallic acid, followed by quercetin, ferulic acid, caffeic acid and rutin. The free radical quenching property of BN leaf extract suggests the presence of bioactive natural compounds.

Concepts: Catechin, Quercetin, Caffeic acid, Resveratrol, Phenols, Ferulic acid, Gallic acid, Vanillin

29

Despite resveratrol’s well-documented health benefits, its mechanism of action remains controversial. In particular, the direct molecular target of resveratrol has been elusive. Park et al. now show that resveratrol directly inhibits cAMP-dependent phosphodiesterases, triggering a cascade of events that converge on the important energy-sensing metabolic regulators AMPK, SIRT1, and PGC-1α.

Concepts: Health insurance, Nutrition, Metaphysics, Resveratrol, Sirtuin 1

28

Bitterness is a major sensory attribute of several common foods and beverages rich in polyphenol compounds. These compounds are reported as very important for health as chemopreventive compounds but they are also known to taste bitter. So, in this work, the activation of the human bitter taste receptors, TAS2Rs, by six polyphenol compounds was analyzed. The compounds chosen are present in a wide range of plant-derived foods and beverages, namely red wine, beer, tea and chocolate. Pentagalloylglucose (PGG) is a hydrolysable tannin, (-)-epicatechin is a precursor of condensed tannins, procyanidin dimer B3 and trimer C2 belong to the condensed tannins, and malvidin-3-glucoside and cyanidin-3-glucoside are anthocyanins. The results show that the different compounds activate different combinations of the ~25 TAS2Rs. (-)-Epicatechin activated three receptors, TAS2R4, TAS2R5 and TAS2R39 whereas only two receptors, TAS2R5 and TAS2R39, responded to PGG. In contrast, malvidin-3-glucoside and procyanidin trimer stimulated only one receptor, TAS2R7 and TAS2R5, respectively. Notably, tannins are the first natural agonists found for TAS2R5 that display high potency only toward this receptor. The catechol and/or galloyl groups appear to be important structural determinants that mediate the interaction of these polyphenolic compounds with TAS2R5. Overall, the EC50 values obtained for the different compounds vary 100-fold with the lowest values for PGG and malvidin-3-glucoside compounds suggesting that they could be significant polyphenols responsible for the bitterness of fruits, vegetables and derived products even if they are present in very low concentrations.

Concepts: Antioxidant, Taste, Tea, Catechin, Resveratrol, Tannin, Polyphenol, Taste receptor

28

The binding sites of antioxidant polyphenols resveratrol, genistein and curcumin are located with milk α- and β-caseins in aqueous solution. FTIR, CD and fluorescence spectroscopic methods and molecular modeling were used to analyse polyphenol binding sites, the binding constant and the effects of complexation on casein stability and conformation. Structural analysis showed that polyphenols bind casein via hydrophilic and hydrophobic interactions with the number of bound polyphenol molecules (n) 1.20 for resveratrol, 1.4 for genistein and 1.4 for curcumin with α-casein and 1.2 for resveratrol, 1.3 for genistein and 1.3 for curcumin with β-casein. The overall binding constants of the complexes formed are Kres-α-casein = 1.9 (± 0.6) x 104 M-1, Kgen-α-casein = 1.8 (± 0.4) x 104 M-1 , Kcur-α-casein = 2.8 (± 0.8) x 104 M-1 with α-casein and Kres-β-casein = 2.3 (± 0.3) x 104 M-1, Kgen-β-casein = 3.0 (± 0.5) x 104 M-1 and Kcur-β-casein = 3.1 (± 0.5) x 104 M-1 for β-casein. Molecular modeling showed the participation of several amino acids in polyphenol-protein complexes, which were stabilized by hydrogen bonding network with the free binding energy of -11.56 (resveratrol-α-casein), -12.35 (resveratrol-β-casein), -9.68 (genistein-α-casein, -9.97 (genistein-β-casein), -8.89 (curcumin-α-casein) and -10.70 kcal/mol (curcumin-β-casein). The binding sites of polyphenols are different with α- and β-caseins. Polyphenol binding altered casein conformation with reduction of α-helix indicating a partial protein destabilization. Caseins might act as carriers to transport polyphenol in vitro.

Concepts: Protein, Antioxidant, Molecule, Chemistry, Atom, Resveratrol, Polyphenol antioxidant, Polyphenol