Food Polyphenols Research Articles

Erratum to: Modulation of Nrf2/ARE Pathway by Food Polyphenols: A Nutritional Neuroprotective Strategy for Cognitive and Neurodegenerative Disorders

Erratum to: Modulation of Nrf2/ARE Pathway by Food Polyphenols: A Nutritional Neuroprotective Strategy for Cognitive and Neurodegenerative Disorders

Reactivity of Human Salivary Proteins Families Toward Food Polyphenols

Tannins are well-known food polyphenols that interact with proteins, namely, salivary proteins. This interaction is an important factor in relation to their bioavailability and is considered the basis of several important properties of tannins, namely, the development of astringency. It has been generally accepted that astringency is due to the tannin-induced complexation and/or precipitation of salivary proline-rich proteins (PRPs) in the oral cavity. However, this complexation is thought to provide protection against dietary tannins. Neverthless, there is no concrete evidence and agreement about which PRP families (acidic, basic, and glycosylated) are responsible for the interaction with condensed tannins. In the present work, human saliva was isolated, and the proteins existing in saliva were characterized by chromatographic and proteomic approaches (HPLC-DAD, ESI-MS, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and MALDI-TOF). These approaches were also adapted to study the affinity of the different families of salivary proteins to condensed tannins by the interaction of saliva with grape seed procyanidins. The results obtained when all the main families of salivary proteins are present in a competitive assay, like in the oral cavity, demonstrate that condensed tannins interact first with acidic PRPs and statherin and thereafter with histatins, glycosylated PRPs, and bPRPs.

Modulation of Nrf2/ARE Pathway by Food Polyphenols: A Nutritional Neuroprotective Strategy for Cognitive and Neurodegenerative Disorders

In recent years, there has been a growing interest, supported by a large number of experimental and epidemiological studies, for the beneficial effects of some phenolic substances, contained in commonly used spices and herbs, in preventing various age-related pathologic conditions, ranging from cancer to neurodegenerative diseases. Although the exact mechanisms by which polyphenols promote these effects remain to be elucidated, several reports have shown their ability to stimulate a general xenobiotic response in the target cells, activating multiple defense genes. Data from our and other laboratories have previously demonstrated that curcumin, the yellow pigment of curry, strongly induces heme-oxygenase-1 (HO-1) expression and activity in different brain cells via the activation of heterodimers of NF-E2-related factors 2 (Nrf2)/antioxidant responsive element (ARE) pathway. Many studies clearly demonstrate that activation ofNrf2 target genes, and particularly HO-1, in astrocytes and neurons is strongly protective against inflammation, oxidative damage, and cell death. In the central nervous system, the HO system has been reported to be very active, and its modulation seems to play a crucial role in the pathogenesis of neurodegenerative disorders. Recent and unpublished data from our group revealed that low concentrations of epigallocatechin-3-gallate, the major green tea catechin, induces HO-1 by ARE/Nrf2 pathway in hippocampal neurons, and by this induction, it is able to protect neurons against different models of oxidative damages. Furthermore, we have demonstrated that other phenolics, such as caffeic acid phenethyl ester and ethyl ferulate, are also able to protect neurons via HO-1 induction. These studies identify a novel class of compounds that could be used for therapeutic purposes as preventive agents against cognitive decline.

The metabolism and analysis of isoflavones and other dietary polyphenols in foods and biological systems

Polyphenols in dietary and botanical matrices are usually present as simple and complex O-glycosides. In fermented dietary materials, the glycosidic moiety is removed and accompanied in some cases by more complex changes to the polyphenol. As for most xenobiotics, polyphenols undergo phase II conjugation in the intestinal wall during their absorption from the gut. In contrast, a few polyphenols, such as puerarin in the kudzu vine, are C-glycosides and are stable in the gut and during absorption, distribution and excretion. Large bowel bacteria reduce polyphenol aglycones, causing opening of the heterocyclic B-ring and ring cleavage. The products are mostly absorbed and enter the bloodstream. Phase I and II metabolism events occur in the intestine and the liver - most polyphenols predominantly circulate as β-glucuronides and sulfate esters with very little as the aglycones, the presumed active forms. In addition, metabolism can occur in non-hepatic tissues and cells including breast tumor cells that have variable amounts of cytochrome P450s, sulfatase and sulfotransferase activities. Inflammatory cells produce chemical oxidants (HOCl, HOBr, ONO(2)(-)) that will react with polyphenols. The isoflavones daidzein and genistein and the flavonol quercetin form mono- and dichlorinated products in reaction with HOCl. Genistein is converted to 3'-nitrogenistein in the lung tissue of lipopolysaccharide-treated rats. Whereas polyphenols that can be converted to quinones or epoxides react with glutathione (GSH) to form adducts, chlorinated isoflavones do not react with GSH; instead, they are converted to β-glucuronides and are excreted in bile. Analysis of polyphenols and their metabolites is routinely carried out with great sensitivity, specificity and quantification by LC-tandem mass spectrometry. Critical questions about the absorption and tissue uptake of complex polyphenols such as the proanthocyanins can be answered by labeling these polyphenols with (14)C-sucrose in plant cell culture and then purifying them for use in animal experiments. The (14)C signature is quantified using accelerator mass spectrometry, a technique capable of detecting one (14)C atom in 10(15) carbon atoms. This permits the study of the penetration of the polyphenols into the interstitial fluid, the fluid that is actually in contact with non-vascular cells.

Recent Applications of Grape Polyphenols in Foods, Beverages and Supplements

Grape polyphenols are associated with the prevention of diseases caused by oxidative stress. The present review discusses the most abundant polyphenols in red grapes as well as the recent food and beverage products developed with these natural antioxidant substances. Grape phenolic concentration and composition depend on agro-geographic factors and processing conditions. In humans, grape polyphenols demonstrated effects such as maintenance of endothelial function, increase in antioxidant capacity and protection against LDL oxidation. Recent patents regarding grape polyphenols show a tendency to return to natural products with a minimum use of severe extraction processes and organic solvents. The new products tend to use grape juice and wine as raw materials and maximize their polyphenolic contents. Grape derived polyphenolic foods, beverages and supplements suit effectively the current demand for antioxidant substances of nutritional interest.

Directly suspended droplet microextraction with in injection-port derivatization coupled to gas chromatography–mass spectrometry for the analysis of polyphenols in herbal infusions, fruits and functional foods

A miniaturized liquid-phase extraction procedure based on directly suspended droplet microextraction is proposed for determining different classes of polyphenols. A derivatization reaction by means of in injection-port reaction with bis(trimethylsilyl)trifluoroacetamide is carried out to convert the polar non-volatile polyphenols into volatile derivatives. The separation and detection is carried out by coupling gas chromatography with mass spectrometry in the selected ion monitoring mode. The procedure uses undecanone, a low density organic solvent, and several factors influencing the extraction, collection efficiency and derivatization reaction are optimized. Excellent linearity was obtained for the range studied (0.05–500 ng mL −1). The limits of detection are between 0.011 and 0.13 ng mL −1, depending on the compound, and the limits of quantification between 0.037 and 0.43 ng mL −1. The sensitivity and detection limits for polyphenols using the DSDME sample pretreatment method were very low. Enrichment factors are between 413 and 578. The recoveries obtained for spiked samples are satisfactory for all the compounds. The coupled miniaturized method is applied to the sensitive determination of both cis- and trans-resveratrol isomers, piceatannol, catechin, epicatechin, quercetin and fisetin in herbal infusions, fruits, juices and functional foods.

Nonextractable polyphenols, usually ignored, are the major part of dietary polyphenols: A study on the Spanish diet

Dietary polyphenols (PP) can be divided into two groups: extractable polyphenols (EPP) or compounds solubilized by aqueous organic solvents, and nonextractable polyphenols (NEPP) or compounds that remain in their corresponding extraction residues. Most studies on food polyphenols and dietary intakes address exclusively EPP. The objective of this work was to determine the actual amount of PP, including NEPP, in food and in a whole diet. HPLC-MS analyses were performed to identify EPP in methanol-acetone extracts and NEPP in the acidic hydrolyzates of their extraction residues in cereals, fruits, vegetables, nuts, and legumes. NEPP contents, estimated as hydrolyzable PP plus nonextractable proanthocyanidins (PA), ranged from 880 mg/100 g dry weight in fruits to 210 mg/100 g in cereals and were substantially higher than the contents of EPP. NEPP intake (day/person) in the Spanish diet (942 mg) is higher than EPP intake (258 mg) fruits and vegetables (746 mg) are the major contributors to the total PP intake (1201 mg). Non extractable polyphenols are the major part of dietary polyphenols. The knowledge of intakes and physiological properties of NEPP may be useful for a better understanding of the potential health effects of dietary PP.

Structure−Activity Relationships of Polyphenols To Prevent Lipid Oxidation in Pelagic Fish Muscle

The influence of polymerization (number of monomers) and galloylation (content of esterified gallates) of oligomeric catechins (proanthocyanidins) on their effectiveness to prevent lipid oxidation in pelagic fish muscle was evaluated. Non-galloylated oligomers of catechin with diverse mean polymerization (1.9-3.4 monomeric units) were extracted from pine (Pinus pinaster) bark. Homologous fractions with galloylation ranging from 0.25 to <1 gallate group per molecule were obtained from grape (Vitis vinifera) and witch hazel (Hamamelis virginiana). The results showed the convenience of proanthocyanidins with medium size (2-3 monomeric units) and low galloylation degree (0.15-0.25 gallate group/molecule) to inhibit lipid oxidation in pelagic fish muscle. These optimal structural characteristics of proanthocyanidins were similar to those lately reported in fish oil-in-water emulsions using phosphatidylcholine as emulsifier. This finding suggests that the antioxidant behavior of polyphenols in muscle-based foods can be mimicked in emulsions prepared with phospholipids as emulsifier agents. The present data give relevant information to achieve an optimum use of polyphenols in pelagic fish muscle.

Recent Applications of Grape Polyphenols in Foods, Beverages and Supplements

Recent Applications of Grape Polyphenols in Foods, Beverages and Supplements

Natural polyphenols antagonize the antimyeloma activity of proteasome inhibitor bortezomib by direct chemical interaction

Bortezomib is a therapeutic proteasome inhibitor with antimyeloma activity and polyphenols are well known compounds that exert antiproliferative effects against tumuors. We attempted to co-treat myeloma cells with bortezomib and polyphenols, anticipating a synergistic effect. However, the anticancer activity of bortezomib was blocked by the polyphenols. The structural features of the polyphenols correlated strikingly with their antagonistic effect; in particular, the presence or absence of a vicinal diol moiety was the key element for effective blockage of the anticancer function of bortezomib. We speculated that the vicinal diols in the polyphenols interact with the boronic acid of bortezomib and convert the active triangular boronic acid of bortezomib to an inactive tetrahedral boronate, thus abolishing the antimyeloma activity of bortezomib. We confirmed this hypothesis by (11)B nuclear magnetic resonance spectroscopy and an in vitro assay on multiple myeloma (MM) cell lines and primary myeloma cells from patients. Based on these findings, restriction of the intake of natural polyphenols in foods or vitamin supplements during bortezomib treatment in MM patients should be considered.

Antioxidant evaluation of O-methylated metabolites of catechin, epicatechin and quercetin

Catechins and quercetin are major polyphenols in many plant foods that have been related to health promotion. In the human organism they are largely metabolized to different metabolites, which are further found in plasma and should contribute to the biological effects associated to the intake of the parent compounds. An important step in quercetin and catechins metabolism is the O-methylation of the catechol group, which can be expected to have an effect on their antioxidant and scavenging properties. In the present work, the 3′- and 4′-methylethers of catechin and epicatechin have been prepared and characterised and their antioxidant activity evaluated and compared to that of the corresponding quercetin derivatives. The antioxidant activity was assessed using the ferric reducing power (FRAP) assay and two methods based on the ability to scavenge the ABTS + radical cation at different pH values. In these assays the three flavonoids behave as better radical scavengers and reducing compounds than usually recognised antioxidants like α-tocopherol. The O-methylation of the hydroxyls of the catechol B-ring resulted in a decrease of the antioxidant activity with regard to the parent compounds. However, the methylated metabolites still retain significant radical scavenging activity at pH 7.4, suggesting that they could act as potential antioxidants in physiological conditions. Quercetin and its methylated metabolites showed, in general, greater activity than (epi)catechin and their O-methyl derivatives, although a relatively high antioxidant activity was found in the case of 3′- O-methyl catechin at pH 7.4, comparable to those of its parent compound and the quercetin metabolites. It was confirmed that the antioxidant activity of the flavonoids assayed was strongly dependent on the pH of the medium, showing higher activity at greater pH values. The results obtained are expected to contribute to the understanding of the mechanisms involved in the biological effects attributed to the intake of flavonoid-rich diets.

Preparation and Characterization of Catechin Sulfates, Glucuronides, and Methylethers with Metabolic Interest

Catechins are major polyphenols in many plant foods that have been related to health promotion. In the human organism they are largely metabolized to different conjugates (sulfates, glucuronides, and methylethers), which are further found in plasma and would contribute to the biological effects associated with the intake of the parent compounds. Circulating metabolites are likely to possess biological properties different from those of the original compounds, and therefore, it is important to evaluate their activity, for which sufficient amounts of them are required that cannot be obtained by isolation from biological fluids. This paper describes the preparation of the methyl, sulfate, and glucuronide derivatives of catechins using different chemical syntheses and their characterization by HPLC-DAD-ESI/MS. MS2 fragmentation of the compounds was also described that allowed the determination of the location of the different substituents on the catechin aglycones. The procedures optimized allowed the preparation of (epi)catechin sulfates, glucuronides, and methylethers conjugated at positions 3' and 4', as well as the sulfates at positions 5 and 7 with satisfactory yields for their further isolation by semipreparative-HPLC in view of their use in in vitro/ex vivo assays.

Ferulaldehyde, a Water-Soluble Degradation Product of Polyphenols, Inhibits the Lipopolysaccharide-Induced Inflammatory Response in Mice

Antiinflammatory properties of polyphenols in natural products, traditional medicines, and healthy foods were recently attributed to highly soluble metabolites produced by the microflora of the intestines rather than the polyphenols themselves. To provide experimental basis for this hypothesis, we measured antiinflammatory properties of ferulaldehyde (FA), a natural intermediate of polyphenol metabolism of intestinal microflora, in a murine lipopolysaccharide (LPS)-induced septic shock model. We found that intraperitoneally administered FA (6 mg/kg) prolonged the lifespan of LPS-treated (40 mg/kg) mice, decreased the inflammatory response detected by T(2)-weighted in vivo MRI, decreased early proinflammatory cytokines such as tumor necrosis factor-alpha and interleukin (IL)-1beta, and increased the antiinflammatory IL-10 in the sera of the mice. Additionally, FA inhibited LPS-induced activation of nuclear factor kappaB transcription factor in the liver of the mice. According to our data, these effects were probably due to attenuating LPS-induced activation of c-Jun N-terminal kinase and Akt. Furthermore, FA decreased free radical and nitrite production in LPS plus interferon-gamma-treated primary mouse hepatocytes, whose effects are expected to contribute to its antiinflammatory property. These data provide direct in vivo evidence, that a water-soluble degradation product of polyphenols could be responsible for, or at least could significantly contribute to, the beneficial antiinflammatory effects of polyphenol-containing healthy foods, natural products, and traditional medicines.

Interaction of Polyphenolic Metabolites with Human Serum Albumin: A Circular Dichroism Study

Binding sites of polyphenolic compounds on human serum albumin (HSA) were investigated using induced Cotton effects on the circular dichroism (CD) spectra. Polyphenolic compounds used in this study are known to be metabolites from tannins and their related polyphenols in food and medicinal plants. The present investigation revealed that the structural differences markedly affected the binding of the compounds to HSA. Protocatechuic acid, together with its methylated compounds vanillic and isovanillic acids, were assigned to be bound to sites I and II of HSA, based on the competitive relationships with site-I-binding phenylbutazone (PB) and site-II-binding diazepam (DP). 4-O-Methylgallic acid, which is the metabolite from gallic acid, was bound to site I on HSA, while gallic acid did not affect the binding of PB and DP at the concentration examined. Neither ellagic acid nor its metabolite urolithin A was competitive with PB and DP on HSA. The addition of digitoxin did not affect the induced CD of the polyphenolic acids examined.

Chemical Studies on Plant Polyphenols and Formation of Black Tea Polyphenols

Recent biological and pharmacological studies strongly suggested that plant polyphenols in foods, beverages and crude drugs have various health benefits. However, still there are chemically uncharacterized polyphenols, especially those with large molecular weights. The typical example is black tea polyphenols. Four tea catechins of fresh tea leaves are enzymatically oxidized in tea fermentation process of black tea manufacture to give a complex mixture of the oxidation products. Despite many efforts since 1950's, major part of the black tea polyphenols has not been clarified yet. We have investigated the oxidation mechanism of each catechin by employing a newly developed in vitro model fermentation system. The oxidation was initiated by enzymatic dehydrogenation of catechins, and subsequent intermolecular quinone-phenol coupling reactions followed by cascade-type degradation of the unstable products resulted in the formation of complex black tea polyphenols. Besides black tea polyphenols, this review introduces the chemistry of insolubilization of persimmon proanthocyanidins, wood polyphenols in connection with whisky polyphenols, and co-polymerization of cinnamaldehyde and proanthocyanidins in cinnamon bark.

Cranberries and Cranberry Products: Powerful in Vitro, ex Vivo, and in Vivo Sources of Antioxidants

Cranberry products and especially cranberry juice (CJ) have been consumed for health reasons primarily due to their effect on urinary tract infections. We investigated the quantity of both free and total (after hydrolysis) phenolic antioxidants in cranberry products using the Folin assay. The order of amount of total polyphenols in cranberry foods on a fresh weight basis was as follows: dried > frozen > sauce > jellied sauce. On a serving size basis for all cranberry products, the order was as follows: frozen > 100% juice > dried > 27% juice > sauce > jellied sauce. High fructose corn syrup (HFCS) is a major source of sugar consumption in the U.S. and contains both glucose and fructose, potential mediators of oxidative stress. We investigated the effect of the consumption of HFCS and ascorbate with CJ antioxidants or without CJ (control) given to 10 normal individuals after an overnight fast. Plasma antioxidant capacity, glucose, triglycerides, and ascorbate were measured 6 times over 7 h after the consumption of a single 240 mL serving of the two different beverages. The control HFCS caused a slight decrease in plasma antioxidant capacity at all time points and thus an oxidative stress in spite of the presence of ascorbate. CJ produced an increase in plasma antioxidant capacity that was significantly greater than control HFCS at all time points. Postprandial triglycerides, due to fructose in the beverages, were mainly responsible for the oxidative stress and were significantly correlated with the oxidative stress as measured by the antioxidant capacity. Cranberries are an excellent source of high quality antioxidants and should be examined in human supplementation studies.

Iron Bioavailability to Piglets from Red and White Common Beans (Phaseolus vulgaris)

Polyphenols in foods may chelate dietary Fe and lower its bioavailability. Concentrations of phenols are higher in red beans than in white beans. The aim of this study was to compare iron bioavailabilities from red and white beans in a piglet hemoglobin repletion model. Fe deficient cross bred piglets (Hampshire x Landrace x Yorkshire) were used. Nutritionally balanced diets (except for Fe) were formulated to contain 50% precooked, dehydrated beans (either small red or Great Northern white). At age 5 weeks, the piglets were assigned to two groups and fed diets containing either red or white beans for 4 weeks. Weight and hemoglobin (Hb) concentrations were monitored weekly. Feed intakes were measured daily. Hemoglobin repletion efficiency (HRE) was calculated as the gain in total body hemoglobin Fe (Hb-Fe) divided by Fe intake. Hb concentrations, Hb-Fe gains, and HRE were not different between the groups at any time point ( p > 0.05). HRE values in the red bean group were 50% in the first week and 30% over the entire 4 week period. In the white bean group, they were 56 and 26%, respectively. Proline-rich protein mRNA concentrations in parotid glands were higher in the red bean group compared to the white bean group. These results show that iron bioavailabilities from red and white beans are similar and suggest that pigs adapt to the inhibitory effects of polyphenols on iron absorption by increasing the secretion of protective proline-rich proteins in the saliva.

Benefits from Dietary Polyphenols for Brain Aging and Alzheimer’s Disease

Brain aging and the most diffused neurodegenerative diseases of the elderly are characterized by oxidative damage, redox metals homeostasis impairment and inflammation. Food polyphenols can counteract these alterations in vitro and are therefore suggested to have potential anti-aging and brain-protective activities, as also indicated by the results of some epidemiological studies. Despite the huge and increasing amount of the in vitro studies trying to unravel the mechanisms of action of dietary polyphenols, the research in this field is still incomplete, and questions about bioavailability, biotransformation, synergism with other dietary factors, mechanisms of the antioxidant activity, risks inherent to their possible pro-oxidant activities are still unanswered. Most of all, the capacity of the majority of these compounds to cross the blood-brain barrier and reach brain is still unknown. This commentary discusses recent data on these aspects, particularly focusing on effects of curcumin, resveratrol and catechins on Alzheimer's disease.

植物性食品の非栄養性機能成分ポリフェノール

植物性食品には多様なポリフェノールが含まれている。その機能は抗酸化能とタンパク質機能調節作用である。有効な抗酸化能を示すポリフェノールはその化学構造にカテコール構造をもつものである。タンパク質機能調節作用は酵素, 受容体, 情報伝達タンパク質などに作用してその機能を調節する効果であるが, これはポリフェノールの立体化学構造によって標的タンパク質が3群に分類される。フェニルプロパノイド類は薬物代謝系の第2相酵素誘導系に, フラボン, フラボノール, アントラキノン類はアリール炭化水素受容体などに, イソフラボンやフラバノン類はエストロゲン受容体などに作用する。ところで, ポリフェノールは非栄養素なので, 体内吸収時にそのほとんどが抱合反応で不活性化される。しかし, 小腸での吸収系を理解して, ポリフェノールを組み合わせるなどのデザインをすれば, 体内で有効な抗酸化能やタンパク質機能調節作用を発揮するポリフェノールを見出すことができる。ここではその機能性を発掘する戦略も議論したい。

Quercetin mediates preferential degradation of oncogenic Ras and causes autophagy in Ha- RAS -transformed human colon cells

Several food polyphenols act as chemopreventers by reducing the incidence of many types of cancer, especially in colon epithelia. In this study, we have investigated whether the flavonoid quercetin can modulate cell proliferation and survival by targeting key molecules and/or biological processes responsible for tumor cell properties. The effect of quercetin on the expression of Ras oncoproteins was specifically studied using systems of either constitutive or conditional expression of oncogenic RAS in human epithelial cells. Our findings suggest that quercetin inhibits cell viability as well as cancer cell properties like anchorage-independent growth. These findings were further supported at the molecular level, since quercetin treatment resulted in a preferential reduction of Ras protein levels in cell lines expressing oncogenic Ras proteins. Notably, in cells that only express wild-type Ras or in those where the oncogenic Ras allele was knocked out, quercetin had no evident effects upon Ras levels. We have shown that quercetin drastically reduces half-life of oncogenic Ras but has no effect when the cells are treated with a proteasome inhibitor. Moreover, in Ha-RAS-transformed cells, quercetin induces autophagic processes. Since quercetin downregulates the levels of oncogenic Ras in cancer cells, we propose that this flavonoid could act as a chemopreventive agent for cancers with frequent mutations of RAS genes.