flavan-3-ol and procyanidin

Results emanating from the synthesis of proanthocyanidins played a crucial role in defining the constitution, regiochemistry, and absolute configuration of this complex but fascinating group of plant secondary metabolites. The initial efforts, commencing in 1966, were focused on structure elucidation of, especially, the procyanidins, profisetinidins, and prorobinetinidins. However, over the past 12 years the emphasis has shifted to the synthesis of the bioactive procyanidins and some of their derivatives at a scale that would permit assessment of their pharmacological properties. With a few exceptions, the vast majority of these synthetic protocols involve the formation of the interflavanyl bond by acid/Lewis acid activation at C-4 of a flavan-3,4-diol or its equivalent, and subsequent trapping of the incipient C-4 carbocation by the nucleophilic centers of a flavan-3-ol (catechin). This review represents the first comprehensive chronicle depicting the development of the subject of proanthocyanidin synthesis.

Topics: Biflavonoids; Catechin; Chemistry, Organic; Flavonoids; History, 20th Century; History, 21st Century; Lewis Acids; Oxidation-Reduction; Plants; Proanthocyanidins; Stereoisomerism; Wood

There is considerable interest in the bioavailability of flavan-3-ols such as tea catechins and cocoa-derived procyanidin components of the diet and their bioactivity in vivo. Their hydrogen-donating abilities and their propensity for nitration make these compounds powerful scavengers of reactive oxygen and nitrogen species. In addition, recent evidence has suggested that these compounds may interact with redox-sensitive cell signaling pathways. However, their bioactivity in vivo will be dependent on the absorption and metabolism of these compounds after ingestion and the reducing properties of resulting metabolites. Many cell, animal, and human studies have shown that flavanol monomers, such as epicatechin, are extensively metabolised to O-methylated forms and/or conjugated to glucuronides and sulphates during absorption into the circulation. The cleavage of higher procyanidin oligomers to mixtures of monomer and dimer in the stomach may act to enhance the potential for their absorption in the small intestine as higher oligomers have very limited absorption. Studies suggest that the major bioactive forms of flavanol monomers and procyanidins in vivo are likely to be metabolites and/or conjugates of epicatechin. One such metabolite, 3'-O-methylepicatechin, has been shown to exert protective effects against oxidative stress-induced cell death. Future studies will continue to concentrate on the exact mechanism of action of the bioactive forms of flavan-3-ols in vivo.

Topics: Animals; Antioxidants; Biflavonoids; Catechin; Digestive System; Flavonoids; Humans; Models, Biological; Models, Chemical; Nitrogen; Oxidation-Reduction; Oxidative Stress; Phenols; Polymers; Proanthocyanidins; Rats; Reactive Oxygen Species; Time Factors

Flavan-3-ols are abundant polyphenols in human nutrition and are associated with beneficial health effects. The aim of this study was to comparatively investigate the metabolic fate of (-)-epicatechin, procyanidin B1, and polymeric procyanidins in a randomized cross-over study in humans.. Parent compounds, conjugates, and microbial metabolites were determined in plasma, urine, and faeces by HPLC-MS and GC-MS/MS. Glucuronidated, sulfated, and methylated (-)-epicatechin and 5-(3',4'-dihydroxyphenyl)-valerolactone were the dominant metabolites in blood and urine. In addition, minor amounts of procyanidin B1 and 4-hydroxy-5-(3',4'-dihydroxyphenyl)valeric acid and their conjugated metabolites were detected. The formation of 5-(3',4'-dihydroxyphenyl)-valerolactone and 4-hydroxy-5-(3',4'-dihydroxyphenyl)valeric acid varied largely between individuals as well as with the degree of polymerization of flavan-3-ols. Monomer units were not detectable in plasma or urine after procyanidin B1 and polymeric procyanidin intake. No correlation was found between the intake of flavan-3-ols and the occurrence of phenolic acids in blood and urine or the phenolic compound profiles in faeces.. In addition to conjugated metabolites derived from the absorption of monomeric flavan-3-ols, 5-(3',4'-dihydroxyphenyl)-valerolactone represents an important in vivo metabolite of (-)-epicatechin and procyanidin B1 produced by the gut microbiota.

Topics: Adult; Biflavonoids; Body Mass Index; Cacao; Catechin; Chromatography, High Pressure Liquid; Creatinine; Cross-Over Studies; Feces; Flavonoids; Humans; Lactones; Male; Plant Extracts; Polymerization; Polymers; Polyphenols; Proanthocyanidins; Tandem Mass Spectrometry; Young Adult

Pulsed electric fields (PEF) have arisen as a promising tool for enhancing plant-based food bioactive compounds, although side effects on quality attributes might compromise consumer acceptance. This work was aimed at filling the gap in the understanding of whole effects of PEF on apple phenolic compounds profile and quality parameters. Treatment specific energy was a critical factor affecting phenolic profile and quality attributes, which in turn varied from 0 to 24 h after treatment. Treatments at 1.8 and 7.3 kJ kg

Topics: Antioxidants; Biflavonoids; Catechin; Chromatography, High Pressure Liquid; Coumaric Acids; Flavonoids; Flavonols; Food Quality; Fruit; Malus; Phenols; Proanthocyanidins; Quinic Acid; Spectrometry, Mass, Electrospray Ionization

Several studies have demonstrated that flavan-3-ol/procyanidins are associated with biological functions in the prevention of various chronic diseases, including obesity and diabetes. Knowledge of their mechanisms, including bioavailability, has significantly progressed in the last decade. However, the differences of the metabolic signatures among flavan-3-ol/procyanidins remain ambiguous.. The metabolites in urine over time after acute administration of three typical flavan-3-ol/procyanidins ((epi)catechin [EPC], epigallocatechin gallate [EGCG], and procyanidin dimer [PC]) in view of the chemical structure were analyzed by HPLC-quadrupole TOF/MS. Several bile acid and amino acid derivatives including tryptophan and tyrosine, as well as flavan-3-ol/procyanidin conjugates and phenolic acid degradation products generated by the gut microbiota were observed in rat urine.. Multivariate statistical analyses suggest that the exogenous and endogenous metabolites of flavan-3-ol/procyanidins greatly differ, although the chemical structures of three typical flavan-3-ol/procyanidins-EPC, EGCG, and PC-are similar. Thus, metabolomic differences likely affect their biological functions and health benefits.

Topics: Animals; Biflavonoids; Catechin; Chromatography, High Pressure Liquid; Flavonoids; Male; Mass Spectrometry; Molecular Weight; Proanthocyanidins; Rats, Wistar

A diverse panel of condensed tannins was used to resolve the confounding effects of size and subunit composition seen previously in tannin-protein interactions. Turbidimetry revealed that size in terms of mean degree of polymerisation (mDP) or average molecular weight (amw) was the most important tannin parameter. The smallest tannin with the relatively largest effect on protein aggregation had an mDP of ~7. The average size was significantly correlated with aggregation of bovine serum albumin, BSA (mDP: r = -0.916; amw: r = -0.925; p<0.01; df = 27), and gelatin (mDP: r = -0.961; amw: r = -0.981; p<0.01; df = 12). The procyanidin/prodelphinidin and cis-/trans-flavan-3-ol ratios gave no significant correlations. Tryptophan fluorescence quenching indicated that procyanidins and cis-flavan-3-ol units contributed most to the tannin interactions on the BSA surface and in the hydrophobic binding pocket (r = 0.677; p<0.05; df = 9 and r = 0.887; p<0.01; df = 9, respectively). Circular dichroism revealed that higher proportions of prodelphinidins decreased the apparent α-helix content (r = -0.941; p<0.01; df = 5) and increased the apparent β-sheet content (r = 0.916; p<0.05; df = 5) of BSA.

Topics: Anthocyanins; Biflavonoids; Catechin; Flavonoids; Gelatin; Hydrophobic and Hydrophilic Interactions; Kinetics; Molecular Structure; Plant Extracts; Plants, Medicinal; Proanthocyanidins; Protein Aggregates; Protein Binding; Serum Albumin, Bovine; Solutions; Tannins; Tryptophan

Medicinal plant materials are not usually analysed for condensed tannins (CT). Thirty commercially available European medicinal plants and herbal products were screened for CT and fourteen CT samples were analysed in detail. This is also the first comprehensive CT analysis of pine buds, walnut leaves, heather flowers and great water dock roots. Acetone/water extracts contained between 3.2 and 25.9 g CT/100g of extract, had CT with mean degrees of polymerisation of 2.9 to 13.3, procyanidin/prodelphinidin ratios of 1.6/98.4 to 100/0 and cis/trans flavan-3-ol ratios of 17.7/82.3 to 97.3/2.7. The majority of samples contained procyanidins, four contained A-type linkages (blackthorn flowers, heather flowers, bilberry leaves and cowberry leaves) and one sample also had galloylated procyanidins (great water dock roots).

Topics: Biflavonoids; Catechin; Europe; Flavonoids; Flowers; Plant Extracts; Plant Leaves; Plant Roots; Plants, Medicinal; Proanthocyanidins; Tannins

Studies with a diverse array of 22 purified condensed tannin (CT) samples from nine plant species demonstrated that procyanidin/prodelphinidin (PC/PD) and cis/trans-flavan-3-ol ratios can be appraised by (1)H-(13)C HSQC NMR spectroscopy. The method was developed from samples containing 44-∼100% CT, PC/PD ratios ranging from 0/100 to 99/1, and cis/trans ratios ranging from 58/42 to 95/5 as determined by thiolysis with benzyl mercaptan. Integration of cross-peak contours of H/C-6' signals from PC and of H/C-2',6' signals from PD yielded nuclei-adjusted estimates that were highly correlated with PC/PD ratios obtained by thiolysis (R(2) = 0.99). cis/trans-Flavan-3-ol ratios, obtained by integration of the respective H/C-4 cross-peak contours, were also related to determinations made by thiolysis (R(2) = 0.89). Overall, (1)H-(13)C HSQC NMR spectroscopy appears to be a viable alternative to thiolysis for estimating PC/PD and cis/trans ratios of CT if precautions are taken to avoid integration of cross-peak contours of contaminants.

Topics: Biflavonoids; Catechin; Flavonoids; Isomerism; Magnetic Resonance Spectroscopy; Plant Extracts; Plants; Proanthocyanidins; Sulfhydryl Compounds

The consumption of polyphenols has frequently been associated with low incidence of degenerative diseases. Most of these natural antioxidants come from fruits, vegetables, spices, grains and herbs. For this reason, there has been increasing interest in identifying plant extract compounds. Polymeric tannins and monomeric flavonoids, such as catechin and epicatechin, in pine bark and green tea extracts could be responsible for the higher antioxidant activities of these extracts. The aim of the present study was to characterize the phenolic compounds in pine bark and green tea concentrated extracts using high-performance liquid chromatography coupled to electrospray ionization mass spectrometry (HPLC-ESI-QTOF-MS). A total of 37 and 35 compounds from pine bark and green tea extracts, respectively, were identified as belonging to various structural classes, mainly flavan-3-ol and its derivatives (including procyanidins). The antioxidant capacity of both extracts was evaluated by three complementary antioxidant activity methods: Trolox equivalent antioxidant capacity (TEAC), ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC). Higher antioxidant activity values by each method were obtained. In addition, total polyphenol and flavan-3-ol contents, which were determined by Folin-Ciocalteu and vanillin assays, respectively, exhibited higher amounts of gallic acid and (+)-catechin equivalents.

Topics: Antioxidants; Biflavonoids; Catechin; Chromatography, High Pressure Liquid; Dimerization; Flavonoids; Phenols; Pinus; Plant Bark; Plant Extracts; Proanthocyanidins; Spectrometry, Mass, Electrospray Ionization; Tea; Time Factors

In this study the permeability of two flavanol-C-glucosides (FCglcs) and five dimeric and trimeric flavan-3-ols, namely, procyanidins (PCs), was investigated with the human colon carcinoma cell line (Caco-2) model. These compounds can be found especially in cocoa, and they are of great interest due to their assumed beneficial health effects. Transepithelial electrical resistance (TEER) and capacitance were measured online with a CellZscope device prior to and during the whole experiment to guarantee the maintenance of the barrier properties. The transport experiments with pure, single compounds (50-300 μM) from apical to basolateral side showed slight permeation of PCs A2, B2, and B5 and cinnamtannin B1 (CB1) as well as (-)-catechin-6-C-glucoside (C6Cglc) and (-)-catechin-8-C-glucoside (C8Cglc) of about 0.02-0.2% after 24 h. Transport of PC C1 could not be detected. Inhibition of P-glycoprotein (Pgp) increased the permeation of PC B2 and CB1 to the basolateral side, which indicates that Pgp counteracts the transport of these compounds. Metabolites (epicatechin, 3'- and 4'-O-epicatechin) in very small amounts were detectable only for PC B2. These are the first data concerning the permeability of flavan-3-ol-C-glucosides across the Caco-2 cell monolayer.

Topics: Biflavonoids; Caco-2 Cells; Catechin; Dimerization; Epithelial Cells; Flavonoids; Glucosides; Humans; Molecular Structure; Permeability; Plant Extracts; Proanthocyanidins

The monomeric flavan-3-ols catechin and epicatechin as well as procyanidins are of great interest due to their potential beneficial health effects observed in epidemiological studies. However, the occurrence and concentration of these compounds is not well-known due to the fact that reference compounds are not commercially available. In this study we determined the pattern and concentration of catechin, epicatechin, and different dimeric and trimeric procyanidins in 38 food samples (nuts, cereals, legumes) using a reversed phase high-performance liquid chromatography electrospray ionization tandem mass spectrometry (RP-HPLC-ESI-MS/MS) approach based on isolated authentic reference compounds. Of the analyzed food samples 21 were found to contain dimeric and trimeric procyanidins and their monomeric building units catechin and epicatechin. Mainly the monitored nut samples contained the analyzed procyanidins as well as catechin and epicatechin whereas only 3 cereals were identified as sources of the analyzed compounds. The concentration ranged from 148 μg/100 g in macadamia nut to 55 mg/100 g in pinto bean. Catechin and procyanidin B3 were found to be the most abundant analytes. The only A-type procyanidin that could be identified was procyanidin A2, which was found in peanut. The achieved data could be used for authenticity control and furthermore in combination with dietary studies to calculate the daily intake of monomeric flavan-3-ols and procyanidins. To our knowledge this is the first detailed study quantifying monomeric flavan-3-ols and dimeric and trimeric procyanidins in various nuts, cereals, and legumes.

Topics: Biflavonoids; Catechin; Chromatography, High Pressure Liquid; Edible Grain; Fabaceae; Flavonoids; Nuts; Plant Extracts; Polymerization; Proanthocyanidins; Tandem Mass Spectrometry

Procyanidins, polymers of flavan-3-ol units, have been reported to exhibit many beneficial health effects such as antioxidant and anti-carcinogenic effects. In this study, we investigated the cancer chemopreventive properties of procyanidins from wild grape (Vitis amurensis) seeds in particular their roles in inducing phase II detoxifying/antioxidant enzymes as well as in modulating the upstream kinases. Ethanolic extract of V. amurensis seeds was fractionated with a series of organic solvents and finally separated into six fractions, F1-F6. Chemical properties of the procyanidins were analyzed by vanillin assay, BuOH-HCl test, and depolymerization with phloroglucinol followed by LC/MS analysis. The F5 had the highest procyanidin content among all the fractions and strongly induced the reporter activity of antioxidant response element as well as the protein expression of nuclear factor E2-related factor (Nrf2) in HepG2 human hepatocarcinoma cells. The procyanidin-rich F5 also strongly induced the expression of the phase II detoxifying and antioxidant enzymes such as NAD(P)H:quinone oxidoreductase1 and hemeoxygenase1. Phosphorylations of the upstream kinases such as MAPKs and PI3K/Akt were significantly increased by treatment with procyanidin fraction. In addition, the procyanidin-mediated Nrf2 expression was partly attenuated by PI3K inhibitor LY294002, and almost completely by p38 inhibitor SB202190, but neither by JNK inhibitor SP600125 nor by MEK1/2 inhibitor U0126. Taken together, the procyanidins from wild grape seeds could be used as a potential natural chemopreventive agent through Nrf2/ARE-mediated phase II detoxifying/antioxidant enzymes induction via p38 and PI3K/Akt pathway.

Topics: Biflavonoids; Catechin; Chromatography, High Pressure Liquid; Chromones; Flavonoids; Gene Expression; Heme Oxygenase-1; Hep G2 Cells; Humans; Mass Spectrometry; Morpholines; NAD(P)H Dehydrogenase (Quinone); NF-E2-Related Factor 2; p38 Mitogen-Activated Protein Kinases; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Proanthocyanidins; Proto-Oncogene Proteins c-akt; Seeds; Signal Transduction; Vitis

A semisynthetic approach for the strategic formation of various procyanidins has been developed. Procyanidin-rich grape seed extracts were reacted with flavan-3-ols under acid catalysis. The reaction enables the formation of dimeric procyanidins and the elimination of higher oligomeric and polymeric procyanidins through degradation. An easy and fast method for the isolation of large amounts of procyanidins after semisynthetic formation by high-speed countercurrent chromatography is presented. Dimeric procyanidins (B1, B2, B3, B4, B5, and B7) were obtained and isolated. Furthermore, galloylated dimeric procyanidins [(-)-epicatechin-3- O-gallate-4beta-->8-(+)-catechin, (-)-epicatechin-3- O-gallate-4beta-->8-(-)-epicatechin, (-)-epicatechin-3- O-gallate-4beta-->6-(-)-epicatechin, and (-)-epicatechin-4beta-->8-(-)-epicatechin-3- O-gallate], as well as trimeric procyanidins [C1, (-)-epicatechin-4beta-->6-(-)-epicatechin-4beta-->8-(-)-epicatechin, and (-)-epicatechin-4beta-->6-(-)-epicatechin-4beta-->6-(+)-catechin] were obtained and isolated as side products. This approach also afforded gambiriins A1 and A2, which were all isolated and unambiguously identified, and the novel 3-(2,4,6-trihydroxyphenyl)-1-(3,4-dihydroxyphenyl)-propan-2-ol-1beta-->8-(-)-epicatechin (gambiriin A4).

Topics: Biflavonoids; Catechin; Dimerization; Flavonoids; Plant Extracts; Proanthocyanidins; Solvents; Vitis

Epidemiological studies have shown that the risk of developing oesophageal adenocarcinoma (OA) is inversely correlated to consumption of fruits and vegetables. Flavan-3-ols are the most abundant subclass of flavonoids in these types of foods. Three apple-derived procyanidin fractions with different average degrees of polymerization (aDP) were characterized and the effects of these fractions and of pure flavan-3-ol monomers ((-)-epicatechin and (+)-catechin) and dimers (B1, B2) on two OA cell lines were investigated. Flavan-3-ol monomers and dimers had no effect on the two cell lines, while apple-derived flavan-3-ol oligomers and polymers induced a time-dependent reduction of cell viability. The reduction in the cell viability was due to the induction of caspase-mediated apoptosis and an arrest of the cell cycle in G0/G1. The magnitude of the reduction in cell viability and induction of apoptosis after exposure to flavan-3-ol oligomeric/polymeric fractions positively correlated with their aDP. These results indicate that only flavan-3-ol oligomers and polymers, but not monomers and dimers, have an effect on the proliferation of OA cells in vitro. As tested flavan-3-ol concentrations are achievable through diet, this study suggests that apple-derived PA may possess chemotherapeutic effects against OA.

Topics: Adenocarcinoma; Apoptosis; Biflavonoids; Catechin; Cell Cycle; Cell Line, Tumor; Cell Survival; Chromatography, High Pressure Liquid; Dimerization; Esophageal Neoplasms; Flavonoids; Humans; Malus; MAP Kinase Signaling System; Polymers; Proanthocyanidins

The adsorption of flavan-3-ol monomers and grape seed procyanidin fractions of different mean degrees of polymerization was studied on three surfaces by means of adsorption isotherms. Reversibility upon dilution was also investigated. These surfaces were three polymeric microfiltration membranes, presenting close Lifshitz-van der Waals components of their surface tension but differing in their surface polar properties. The electron-donor character of the surface was of primary importance for the adsorption of nongalloylated monomers. Increasing the number of phenolic rings above two (galloylated monomers and procyanidins) sharply enhanced flavan-3-ol affinity for surfaces whatever their polarity. However, maximum adsorbed amounts were always much higher on the most polar material. The general trend was a partial reversibility with monomers, whereas an irreversible process was evidenced from the lowest molecular weight tannin fractions. This indicated the formation of multiple bonds with surfaces, in accordance with the high affinity type isotherms. The whole results indicated very different mechanisms in the buildup of the adsorbed layers when the surface electron-donor character varied.

Topics: Adsorption; Biflavonoids; Catechin; Chemical Phenomena; Chemistry, Physical; Flavonoids; Kinetics; Proanthocyanidins; Seeds; Solvents; Surface Properties; Vitis

In the United States, commercially available foods, including cocoa and chocolate, are being marketed with statements referring to the level of antioxidant activity and polyphenols. For cocoa-containing foods, there has been no comprehensive survey of the content of these and other chemistries. A survey of cocoa and chocolate-containing products marketed in the United States was conducted to determine antioxidant activity and polyphenol and procyanidin contents. Commercially available samples consisted of the top market share products in each of the following six categories: natural cocoa, unsweetened baking chocolate, dark chocolate, semisweet baking chips, milk chocolate, and chocolate syrup. Composite samples were characterized using four different methods: oxygen radical absorbance capacity (ORAC), vitamin C equivalence antioxidant capacity (VCEAC), total polyphenols, and procyanidins. All composite lots were further characterized for percent nonfat cocoa solids (NFCS) and percent fat. Natural cocoas had the highest levels of antioxidant activities, total polyphenols, and procyanidins followed by baking chocolates, dark chocolates and baking chips, and finally milk chocolate and syrups. The results showed a strong linear correlation between NFCS and ORAC (R (2) = 0.9849), total polyphenols (R (2) = 0.9793), and procyanidins (R (2) = 0.946), respectively. On the basis of principal component analysis, 81.4% of the sample set was associated with NFCS, antioxidant activity, total polyphenols, and procyanidins. The results indicated that, regardless of the product category, NFCS were the primary factor contributing to the level of cocoa antioxidants in the products tested. Results further suggested that differences in cocoa bean blends and processing, with the possible exception of Dutching, are minor factors in determining the level of antioxidants in commercially available cocoa-containing products in the United States.

Topics: Antioxidants; Ascorbic Acid; Biflavonoids; Cacao; Catechin; Flavonoids; Phenols; Polyphenols; Proanthocyanidins; Reactive Oxygen Species; United States

A low sodium diet has often been implicated in the protection of low blood pressure populations from hypertension, but several other dietary factors, including those as yet unidentified, may also be involved. The Kuna Indians of Panama are free of hypertension and cardiovascular disease, but this is changing with migration to urban areas. We compared the indigenous diet of Kuna Indians living on remote islands in Panama (Ailigandi), whose lifestyle is largely hunter-gatherer, with those who have moved to a suburb of Panama City (Vera Cruz). Between April and October 1999, members of a Kuna research team administered a 118-item food frequency questionnaire to133 adult Kuna from Ailigandi and 183 from Vera Cruz. Single 24-hour urine collections and nonfasting blood samples were obtained. The Kuna in Ailigandi reported consuming a 10-fold higher amount of cocoa-containing beverages, 4 times the amount of fish, and twice the amount of fruit as urban Kuna (P<0.05 by t test). Salt added was ample among those living in Ailigandi and Vera Cruz according to both self-report (7.1+/-1.1 and 4.6+/-0.3 tsp weekly) and urinary sodium levels (177+/-9 and 160+/-7 mEq Na/g creatinine), respectively. The low blood pressure of island-dwelling Kuna does not seem to be related to a low salt diet. Among dietary factors that varied among migrating Kuna, the notably higher intake of flavanol-rich cocoa is a potential candidate for further study.

Topics: Acculturation; Adult; Animals; Beverages; Biflavonoids; Cacao; Catechin; Diet; Diet Surveys; Female; Fishes; Flavonoids; Fruit; Humans; Hypertension; Indians, Central American; Male; Middle Aged; Panama; Proanthocyanidins; Sodium, Dietary; Vegetables

Catechins (flavanols) are strong antioxidants, free radical scavengers and inhibitors of lipid peroxidation. New bio-based antioxidant compounds obtained by depolymerization of plant polymeric flavanols (procyanidins) in the presence of cysteine or cysteamine, as well as their underivatized counterpart, (-)-epicatechin, were evaluated in terms of their percutaneous absorption profiles taking into account their free radical scavenging efficiency. The evaluation of the percutaneous absorption of flavanols was carried out by an in vitro methodology using both pig and human skin. A good correlation was obtained using both skins in the evaluation of the skin absorption profiles. It can be deduced that 4beta-(S-cysteinyl)epicatechin (Cys-Ec) has a tendency to be located mainly in the outermost layers of the skin, whereas 4beta-(2-aminoethylthio)epicatechin (Cya-Ec) has a pronounced percutaneous absorption capacity. Their antioxidant properties and their skin penetration profiles support their potential cosmetic or pharmacological applications.

Topics: Animals; Biflavonoids; Catechin; Chromatography, High Pressure Liquid; Flavonoids; Free Radical Scavengers; Humans; In Vitro Techniques; Molecular Structure; Proanthocyanidins; Skin; Skin Absorption; Swine; Tissue Distribution

Procyanidins extracted from cocoa play a role in the defense against oxidative stress, as well as in vascular and immune functions. We previously reported that pentameric procyanidins isolated from cocoa inhibit the expression of the tyrosine kinase ErbB2 gene, thus slowing the growth of cultured human aortic endothelial cells. We herein investigate the further consequences of such inhibition by cocoa procyanidins, particularly regarding the protein level in phosphorylation patterns and the effects on the proliferation of human dermal microvascular endothelial cells (HDMECs) following angiogenic stimulation with low-level H2O2. We report herein that both the pentameric and octameric procyanidin fractions of cocoa inhibit the proliferation of HDMECs, whereas the pentameric fraction modulates the activity of several crucial proteins in angiogenic signaling by altering their tyrosine phosphorylation. Similar to aortic endothelial cells, the pentameric procyanidin fraction down-regulates the expression of ErbB2 tyrosine kinase in HDMECs. In conclusion, we report evidence suggesting that polyphenols may influence endothelial growth signaling, thus affecting angiogenesis in vitro. If these observations are applicable in vivo, they suggest a beneficial effect for cells overexpressing ErbB2, such as in specific neoplasias

Topics: Biflavonoids; Cacao; Catechin; Cell Division; DNA Primers; Endothelium, Vascular; Flavonoids; Humans; Hydrogen Peroxide; Microcirculation; Neovascularization, Physiologic; Proanthocyanidins; Receptor, ErbB-2; Reverse Transcriptase Polymerase Chain Reaction; Skin

Separation of the water-soluble fraction of peanut skins led to the isolation of five proanthocyanidins. Based on the spectroscopic investigation and partial acid catalyzed degradation, their structures were determined to be epicatechin-(2beta-->O -->7, 4beta -->6)-[epicatechin-(4beta-->8)]-catechin (1), epicatechin-(2beta-->O -->7, 4beta-->8) epicatechin-(4beta-->8)-catechin-(4alpha-->8)-epicatechin (2), and procyanidins B2 (3), B3 (4) and B4 (5). The absolute configuration of the new compounds was determined from their circular dichroism curves and the (1)H NMR spectra of analysis of flavan-3-ols formed by thiolytic degradation of 1 and 2 in the presence of a chiral dirhodium complex (dirhodium tetra-(R)-(trifluoromethyl) phenyl acetate).

Topics: Antioxidants; Arachis; Biflavonoids; Catechin; Circular Dichroism; Flavonoids; Free Radical Scavengers; Magnetic Resonance Spectroscopy; Phenols; Polyphenols; Proanthocyanidins; Rhodium; Sulfhydryl Reagents

Cocoa flavanols and procyanidins have numerous biological activities. It is known that (-)-epicatechin, (+)-catechin, epicatechin-(4beta-8)-epicatechin (dimer B2), and epicatechin-(4beta-6)-epicatechin (dimer B5) are unstable at physiologic pH, degrading almost completely within several hours, whereas they are relatively stable at pH 5.0. The present study investigated the effects of ascorbic and citric acid on the stability of monomers and dimers in simulated intestinal juice (pH 8.5) and in sodium phosphate buffer (pH 7.4). The addition of ascorbic acid to the incubation mixture significantly increased the stability of the monomers and dimers, whereas the addition of citric acid provided no protective effects. LC-MS showed that with the degradation of dimer B2 and dimer B5, doubly linked A-type dimers were formed. The present results, although not directly transferable to in vivo conditions, suggest that ascorbic acid may stabilize cocoa flavanols and procyanidins in the intestine where the pH is neutral, or alkaline, before absorption.

Topics: Ascorbic Acid; Biflavonoids; Body Fluids; Cacao; Catechin; Citric Acid; Dimerization; Drug Stability; Flavonoids; Hydrogen-Ion Concentration; Intestines; Proanthocyanidins

The monomeric, oligomeric, and polymeric flavan-3-ol composition of wines, grape seeds, and skins from Vitis vinifera L. cv. Graciano, Tempranillo, and Cabernet Sauvignon has been studied using (1) fractionation by polyamide column chromatography followed by HPLC/ESI-MS analysis, (2) fractionation on C(18) Sep-Pak cartridges followed by reaction with vanillin and acid-catalyzed degradation in the presence of toluene-alpha-thiol (thiolysis). The content of monomers ((+)-catechin and (-)-epicatechin), procyanidin dimers (B3, B1, B4, and B2), trimers (T2 and C1), and dimer gallates (B2-3-O-gallate, B2-3'-O-gallate, and B1-3-O-gallate) ranged from 76.93 to 133.18 mg/L in wines, from 2.30 to 8.21 mg/g in grape seeds, and from 0.14 to 0.38 mg/g in grape skins. In wines, the polymeric fraction represented 77-84% of total flavan-3-ols and showed a mean degree of polymerization (mDP) value of 6.3-13.0. In grapes, the polymeric fraction represented 75-81% of total flavan-3-ols in seeds and 94-98% in skins and showed mDP values of 6.4-7.3 in seeds and 33.8-85.7 in skins. All the monomeric flavan-3-ols and oligomeric procyanidins found in wines were also present in seeds, although differences in their relative abundances were seen. The skin polymeric proanthocyanidins participated in the equilibration of the wine polymeric proanthocyanidin fraction, especially contributing to the polymer subunit composition and mDP.

Topics: Biflavonoids; Catechin; Chromatography, High Pressure Liquid; Flavonoids; Fruit; Hydrogen-Ion Concentration; Polymers; Proanthocyanidins; Seeds; Spectrometry, Mass, Electrospray Ionization; Toluene; Vitis; Wine

It was determined that flavan-3-ols and procyanidins have an inhibitory effect on angiotensin I converting enzyme (ACE) activity, and the effect was dependent on the number of epicatechin units forming the procyanidin. The inhibition by flavan-3-ols and procyanidins was competitive with the two substrates assayed: N-hippuryl-L-histidyl-L-leucine (HHL) and N-[3-(2-furyl)acryloyl]-L-phenylalanylglycylglycine (FAPGG). Tetramer and hexamer fractions were the more potent inhibitors, showing Ki of 5.6 and 4.7 microM, respectively. As ACE is a membrane protein, the interaction of flavanols and procyanidins with the enzyme could be related to the number of hydroxyl groups on the procyanidins, which determine their capacity to be adsorbed on the membrane surface.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Biflavonoids; Binding Sites; Binding, Competitive; Catechin; Flavonoids; Inhibitory Concentration 50; Kinetics; Lung; Peptidyl-Dipeptidase A; Proanthocyanidins; Rabbits; Substrate Specificity; Thermodynamics

The flavan-3-ols (-)-epicatechin (epicatechin) and (+)-catechin (catechin) and their related oligomers (procyanidins) isolated from cocoa were assayed for their capacity to inhibit the UVC-mediated formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (oxo(8)dG) in calf thymus DNA. The above-mentioned compounds inhibited oxo(8)dG production in a concentration- and time-dependent manner. After 30 min of irradiation (30 kJ/m(2)), 0.1, 1.0, 10, and 100 microM epicatechin inhibited oxo(8)dG formation by 20, 36, 64, and 74%, respectively. For the same dose of UVC, 0.1, 1.0, 10, and 100 microM catechin inhibited oxo(8)dG formation by 1, 23, 50, and 70%, respectively. Epicatechin was more efficient than catechin with respect to inhibiting oxo(8)dG formation (IC(50) 1.7 +/- 0.7 vs 4.0 +/- 0.7 microM). Monomer, tetramer, and hexamer fractions were equally effective in inhibiting oxo(8)dG formation when assayed at 10 microM monomer equivalent concentration. At similar concentrations (1-50 microM), the inhibition of the UVC-mediated oxo(8)dG formation by flavan-3-ols and procyanidins was in the range of that of alpha-tocopherol, Trolox, ascorbate, and glutathione. These results support the concept that flavan-3-ols and their related procyanidins can protect DNA from oxidation at concentrations that can be physiologically relevant. Both epimerism and degree of oligomerization are important determinants of the antioxidant activity of flavan-3-ols and procyanidins.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Biflavonoids; Catechin; Cattle; Deoxyguanosine; DNA; DNA Damage; Dose-Response Relationship, Drug; Flavonoids; Kinetics; Proanthocyanidins; Thymus Gland; Ultraviolet Rays

Epidemiological reports have suggested that the consumption of foods rich in flavonoids is associated with a lower incidence of certain degenerative diseases, including cardiovascular disease. Flavanols and their related oligomers, the procyanidins CFP, isolated from cocoa can modulate the production and level of several signaling molecules associated with immune function and inflammation in vitro, including several cytokines and eicosanoids. To further elucidate the potential immuno-modulatory functions of flavanol-rich cocoa, the present investigation examined whether isolated CFP fractions (monomers through decamers) influence the secretion of tumor necrosis factor-alpha (TNF-alpha) from resting and phytohemagluttinin (PHA)-stimulated human peripheral blood mononuclear cells (PBMC). We used an in vitro culture system where PBMC from 14 healthy subjects were introduced to individual CFP fractions for 72 h prior to measuring the levels of TNF-alpha released. The intermediate-sized CFP fractions (tetramers through octamers) were the most active on resting cells, causing a 3-4 fold increase in TNF-alpha relative to media baseline. The monomers and dimers were the least stimulatory of the fractions tested, displaying a 42 and 31% increase, respectively, over media control, whereas the trimers, nonamers and decamers showed an intermediate stimulation of this cytokine. In the presence of PHA, the intermediate-sized CFP fractions again were the most active, enhancing TNF-alpha secretion in the range of 48-128% relative to the PHA control. The monomers and dimers were slightly inhibitory (-1.5 and -15%, respectively), while trimers, nonamers and decamers stimulated moderate increases in TNF-alpha levels (13, 19 and 15%, respectively). The above results lend support to the concept that CFP can be immunomodulatory. The stimulation of TNF-alpha secretion may contribute to the putative beneficial effects of dietary flavanoids against microbial infection and tumorigenesis.

Topics: Biflavonoids; Cacao; Catechin; Cells, Cultured; Dimerization; Flavonoids; Humans; Leukocytes, Mononuclear; Proanthocyanidins; Tumor Necrosis Factor-alpha

The effects of cocoa powder and extracts with different amounts of flavanols and related procyanidin oligomers were investigated on the growth of Caco-2 cells. Treatment of the cells with 50 microg/ml of procyanidin-enriched (PE) extracts caused a 70% growth inhibition with a blockade of the cell cycle at the G2/M phase. PE extracts caused a significant decrease of ornithine decarboxylase and S-adenosylmethionine decarboxylase activities, two key enzymes of polyamine biosynthesis. This led to a decrease in the intracellular pool of the polyamines. These observations indicate that polyamine metabolism might be an important target in the anti-proliferative effects of cocoa polyphenols.

Topics: Antineoplastic Agents; Antioxidants; Apoptosis; Biflavonoids; Cacao; Catechin; Cell Division; Cell Survival; Colonic Neoplasms; Flavonoids; Humans; Kinetics; Phytotherapy; Plant Extracts; Polyamines; Proanthocyanidins; Tumor Cells, Cultured

New bio-based antioxidant compounds have been obtained by depolymerisation of grape polymeric flavanols in the presence of cysteine. Their preparation and purification, as well as their antiradical/antioxidant and antiproliferative properties are reported. 4beta-(S-cysteinyl)epicatechin 5, 4beta-(S-cysteinyl)catechin 6 and 4beta-(S-cysteinyl)epicatechin 3-O-gallate 7 were efficiently purified from the crude depolymerised mixture by cation-exchange chromatography and preparative reversed-phase chromatography. The new compounds were more efficient than the underivatised (-)-epicatechin 1 as scavengers of the 1,1-diphenyl-2-picrylhydrazyl free radical (DPPH) and weak growth inhibitors of human colon carcinoma HT29 cells. The order of antiradical and antiproliferative efficiency was 7 >5 approximately 6 >1, the same for both assays.

Topics: Antineoplastic Agents; Antioxidants; Biflavonoids; Biphenyl Compounds; Catechin; Cell Division; Cysteine; Flavonoids; Free Radical Scavengers; Humans; Picrates; Proanthocyanidins; Structure-Activity Relationship; Tumor Cells, Cultured; Vitis