Showing papers in "Molecular Nutrition & Food Research in 2009"

Phytate in foods and significance for humans: food sources, intake, processing, bioavailability, protective role and analysis.

Abstract: The article gives an overview of phytic acid in food and of its significance for human nutrition. It summarises phytate sources in foods and discusses problems of phytic acid/phytate contents of food tables. Data on phytic acid intake are evaluated and daily phytic acid intake depending on food habits is assessed. Degradation of phytate during gastro-intestinal passage is summarised, the mechanism of phytate interacting with minerals and trace elements in the gastro-intestinal chyme described and the pathway of inositol phosphate hydrolysis in the gut presented. The present knowledge of phytate absorption is summarised and discussed. Effects of phytate on mineral and trace element bioavailability are reported and phytate degradation during processing and storage is described. Beneficial activities of dietary phytate such as its effects on calcification and kidney stone formation and on lowering blood glucose and lipids are reported. The antioxidative property of phytic acid and its potentional anticancerogenic activities are briefly surveyed. Development of the analysis of phytic acid and other inositol phosphates is described, problems of inositol phosphate determination and detection discussed and the need for standardisation of phytic acid analysis in foods argued.

Tannins: current knowledge of food sources, intake, bioavailability and biological effects.

Abstract: Tannins are a unique group of phenolic metabolites with molecular weights between 500 and 30 000 Da, which are widely distributed in almost all plant foods and beverages. Proanthocyanidins and hydrolysable tannins are the two major groups of these bioactive compounds, but complex tannins containing structural elements of both groups and specific tannins in marine brown algae have also been described. Most literature data on food tannins refer only to oligomeric compounds that are extracted with aqueous-organic solvents, but a significant number of non-extractable tannins are usually not mentioned in the literature. The biological effects of tannins usually depend on their grade of polymerisation and solubility. Highly polymerised tannins exhibit low bioaccessibility in the small intestine and low fermentability by colonic microflora. This review summarises a new approach to analysis of extractable and non-extractable tannins, major food sources, and effects of storage and processing on tannin content and bioavailability. Biological properties such as antioxidant, antimicrobial and antiviral effects are also described. In addition, the role of tannins in diabetes mellitus has been discussed.

Carotenoids: Actual knowledge on food sources, intakes, stability and bioavailability and their protective role in humans

Abstract: Carotenoids are one of the major food micronutrients in human diets and the overall objective of this review is to re-examine the role of carotenoids in human nutrition. We have emphasized the attention on the following carotenoids present in food and human tissues: beta-carotene, beta-cryptoxanthin, alpha-carotene, lycopene, lutein and zeaxanthin; we have reported the major food sources and dietary intake of these compounds. We have tried to summarize positive and negative effects of food processing, storage, cooking on carotenoid content and carotenoid bioavailability. In particular, we have evidenced the possibility to improve carotenoids bioavailability in accordance with changes and variations of technology procedures.

Glucosinolates in Brassica Vegetables - the Influence of the Food Supply Chain on Intake, Bioavailability and Human Health

Abstract: Glucosinolates (GLSs) are found in Brassica vegetables. Examples of these sources include cabbage, Brussels sprouts, broccoli, cauliflower and various root vegetables (e.g. radish and turnip). A number of epidemiological studies have identified an inverse association between consumption of these vegetables and the risk of colon and rectal cancer. Animal studies have shown changes in enzyme activities and DNA damage resulting from consumption of Brassica vegetables or isothiocyanates, the breakdown products (BDP) of GLSs in the body. Mechanistic studies have begun to identify the ways in which the compounds may exert their protective action but the relevance of these studies to protective effects in the human alimentary tract is as yet unproven. In vitro studies with a number of specific isothiocyanates have suggested mechanisms that might be the basis of their chemoprotective effects. The concentration and composition of the GLSs in different plants, but also within a plant (e.g. in the seeds, roots or leaves), can vary greatly and also changes during plant development. Furthermore, the effects of various factors in the supply chain of Brassica vegetables including breeding, cultivation, storage and processing on intake and bioavailability of GLSs are extensively discussed in this paper.

International epidemiology of prostate cancer: geographical distribution and secular trends.

Abstract: This review outlines current international patterns in prostate cancer incidence and mortality rates and survival, including recent trends and a discussion of the possible impact of prostate-specific antigen (PSA) testing on the observed data. Internationally, prostate cancer is the second most common cancer diagnosed among men (behind lung cancer), and is the sixth most common cause of cancer death among men. Prostate cancer is particularly prevalent in developed countries such as the United States and the Scandinavian countries, with about a six-fold difference between high-incidence and low-incidence countries. Interpretation of trends in incidence and survival are complicated by the increasing impact of PSA testing, particularly in more developed countries. As Western influences become more pronounced in less developed countries, prostate cancer incidence rates in those countries are tending to increase, even though the prevalence of PSA testing is relatively low. Larger proportions of younger men are being diagnosed with prostate cancer and living longer following diagnosis of prostate cancer, which has many implications for health systems. Decreasing mortality rates are becoming widespread among more developed countries, although it is not clear whether this is due to earlier diagnosis (PSA testing), improved treatment, or some combination of these or other factors.

Pharmacokinetic and safety profile of trans‐resveratrol in a rising multiple‐dose study in healthy volunteers

Abstract: This was a double-blind, randomised, placebo-controlled study to investigate the pharmacokinetics and safety of trans-resveratrol. In four groups of ten healthy adult subjects (five males and five females), two subjects were randomized to receive placebo and eight subjects to receive trans-resveratrol 25, 50, 100 or 150 mg, six times/day, for thirteen doses. Peak plasma concentrations of trans-resveratrol were reached at 0.8-1.5 h postdose. Following the 13th dose of trans-resveratrol 25, 50, 100 and 150 mg, mean peak plasma concentration (C(max)) was 3.89, 7.39, 23.1 and 63.8 ng/mL and mean area under the plasma concentration-time curve (AUC(0-tau)) was 3.1, 11.2, 33.0 and 78.9 ng.h/mL. Interindividual variability was high, with coefficients of variation >40%. Trans-resveratrol half-life was 1-3 h following single-doses and 2-5 h following repeated dosing. Trough (C(min)) concentrations were < or = 1 ng/mL following 25 and 50 mg, 3 ng/mL following 100 mg and < 10 ng/mL following 150 mg. Trans-resveratrol pharmacokinetics showed circadian variation. Adverse events were mild in severity and similar between all groups. In conclusion, repeated administration was well-tolerated but produced relatively low plasma concentrations of trans-resveratrol, despite the high doses and short dosing interval used. Bioavailability was higher after morning administration.

Resveratrol addiction: To die or not to die

Abstract: Resveratrol, a polyphenol derived from red grapes, berries, and peanuts, has been shown to mediate death of a wide variety of cells. The mechanisms by which resveratrol mediates cell death include necrosis, apoptosis, autophagy, and others. While most studies suggest that resveratrol kills tumor cells selectively, evidence is emerging that certain normal cells such as endothelial cells, lymphocytes, and chondrocytes are vulnerable to resveratrol. Cell killing by this stilbene may be mediated through any of numerous mechanisms that involve activation of mitochondria and of death caspases; upregulation of cyclin-dependent kinase inhibitors, tumor suppressor gene products, or death-inducing cytokines and cytokine receptors; or downregulation of cell survival proteins (survivin, cFLIP, cIAPs, X-linked inhibitor of apoptosis protein (XIAP), bcl-2, bcl-XL) or inhibition of cell survival kinases (e.g., mitogen-activiated protein kinases (MAPKs), AKT/phosphoinositide 3-kinase (PI3K), PKC, EGFR kinase) and survival transcription factors (nuclear factor-kappaB (NF-kappaB), activating protein 1 (AP-1), HIF-1alpha, signal transducer and activator of transcription (STAT3)). Induction of any of these pathways by resveratrol leads to cell death. While cell death is a hallmark of resveratrol, this polyphenol also has been linked with suppression of inflammation, arthritis, and cardiovascular diseases and delaying of aging. These attributes of resveratrol are discussed in detail in this review.

Status of groundwater arsenic contamination in the state of West Bengal, India: A 20‐year study report

Abstract: Since 1988 we have analyzed 140 150 water samples from tube wells in all 19 districts of West Bengal for arsenic; 48.1% had arsenic above 10 μg/L (WHO guideline value), 23.8% above 50 μg/L (Indian Standard) and 3.3% above 300 μg/L (concentration predicting overt arsenical skin lesions). Based on arsenic concentrations we have classified West Bengal into three zones: highly affected (9 districts mainly in eastern side of Bhagirathi River), mildly affected (5 districts in northern part) and unaffected (5 districts in western part). The estimated number of tube wells in 8 of the highly affected districts is 1.3 million, and estimated population drinking arsenic contaminated water above 10 and 50 μg/L were 9.5 and 4.2 million, respectively. In West Bengal alone, 26 million people are potentially at risk from drinking arsenic-contaminated water (above 10 μg/L). Studying information for water from different depths from 107 253 tube wells, we noted that arsenic concentration decreased with increasing depth. Measured arsenic concentration in two tube wells in Kolkata for 325 and 51 days during 2002–2005, showed 15% oscillatory movement without any long-term trend. Regional variability is dependent on sub-surface geology. In the arsenic-affected flood plain of the river Ganga, the crisis is not having too little water to satisfy our needs, it is the crisis of managing the water.

Polyphenol metabolites from colonic microbiota exert anti-inflammatory activity on different inflammation models.

Abstract: The polyphenols in fruits and vegetables may be partly responsible for the health-promoting effects attributed to fruit and vegetable intake. Although their properties have been relatively well studied, the activity of their metabolites, produced after ingestion, has been poorly investigated. Thus, the aim of this work was to study the potential anti-inflammatory effect of 18 polyphenol metabolites, derived from colon microbiota. They were screened by measuring prostaglandin E(2) (PGE(2)) production by CCD-18 colon fibroblast cells stimulated with IL-1beta. Metabolites that inhibited more than 50% PGE(2) production were hydrocaffeic (HCAF), dihydroxyphenyl acetic (dOHPA), and hydroferulic acid (HFER), that subsequently were tested with the writhing and paw pressure test in rodents where all three compounds showed an anti-inflammatory effect. The effect of HCAF administered orally (50 mg/kg) was also tested in the dextran sodium sulfate (DSS)-induced colitis model. Weight loss and fecal water content were more pronounced in DSS rats than in DSS-HCAF treated rats. HCAF treatment diminished the expression of the cytokines IL-1beta, IL-8, and TNF-alpha, reduced malonyldialdehyde (MDA) levels and oxidative DNA damage (measured as 8-oxo-2'-deoxyguanosine levels) in distal colon mucosa. These results indicate that HCAF, dOHPA, and HFER have anti-inflammatory activity in vitro and in vivo.

In vitro digestion methods for assessing the effect of food structure on allergen breakdown

Abstract: This article reviews the in vitro digestion models developed to assess the stability of food allergens during digestion. It is hypothesised that food allergens must exhibit sufficient gastro-intestinal stability to reach the intestinal mucosa where absorption and sensitisation (development of atopy) can occur. The investigation of stability of proteins within the gastrointestinal tract may provide prospective testing for allergenicity and could be a significant and valid parameter that distinguishes food allergens from nonallergens. Systematic evaluation of the stability of food allergens that are active via the gastrointestinal tract is currently tested in traditional pepsin digestibility models. The human gastrointestinal tract however is very complex and this article points out the importance of using physiologically relevant in vitro digestion systems for evaluating digestibility of allergens. This would involve the simulation of the stomach/small intestine environment (multi-phase models) with sequential addition of digestive enzymes, surfactants such as phospholipids and bile salts under physiological conditions, as well as the consideration of the effect of the food matrices on the allergen digestion.

Absorption, metabolism and excretion of Choladi green tea flavan-3-ols by humans

Abstract: Ten healthy human subjects consumed 500 mL of Choladi green tea, containing 648 mumol of flavan-3-ols after which plasma and urine were collected over a 24 h period and analysed by HPLC-MS. Plasma contained a total of ten metabolites, in the form of O-methylated, sulphated and glucuronide conjugates of (epi)catechin and (epi)gallocatechin, with 29-126 nM peak plasma concentrations (C(max)) occurring 1.6-2.3 h after ingestion, indicative of absorption in the small intestine. Plasma also contained unmetabolised (-)-epigallocatechin-3-gallate and (-)-epicatechin-3-gallate with respective C(max) values of 55 and 25 nM. Urine excreted 0-24 h after consumption of green tea contained 15 metabolites of (epi)catechin and (epi)gallocatechin, but (-)-epigallocatechin-3-gallate and (-)-epicatechin-3-gallate were not detected. Overall flavan-3-ol metabolite excretion was equivalent to 8.1% of intake, however, urinary (epi)gallocatechin metabolites corresponded to 11.4% of (epi)gallocatechin ingestion while (epi)catechin metabolites were detected in amounts equivalent to 28.5% of (epi)catechin intake. These findings imply that (epi)catechins are highly bioavailable, being absorbed and excreted to a much greater extent than most other flavonoids. It is also evident that flavan-3-ol metabolites are rapidly turned over in the circulatory system and as a consequence C(max) values are not an accurate quantitative indicator of the extent to which absorption occurs.

Thioredoxin system inhibitors as mediators of apoptosis for cancer therapy

Abstract: The thioredoxin (Trx) system is a major antioxidant system integral to maintaining the intracellular redox state. It contains Trx, a redox active protein, which regulates the activity of various enzymes including those that function to counteract oxidative stress within the cell. Trx can also scavenge reactive oxygen species (ROS) and directly inhibits proapoptotic proteins such as apoptosis signal-regulating kinase 1 (ASK1). The oxidized form of Trx is reduced by thioredoxin reductase (TrxR). The cytoplasm and mitochondria contain equivalent Trx systems and inhibition of either system can lead to activation of apoptotic signaling pathways. There are a number of inhibitors with chemotherapy applications that target either Trx or TrxR to induce apoptosis in cancer cells. Suberoylanilide hydroxamic acid (SAHA) is effective against many cancer cells and functions by up-regulating an endogenous inhibitor of Trx. Other compounds target the selenocysteine-containing active site of TrxR. These include gold compounds, platinum compounds, arsenic trioxide, motexafin gadolinium, nitrous compounds, and various flavonoids. Inhibition of TrxR leads to an accumulation of oxidized Trx resulting in cellular conditions that promote apoptosis. In addition, some compounds also convert TrxR to a ROS generating enzyme. The role of Trx system inhibitors in cancer therapy is discussed in this review.

The complex links between dietary phytochemicals and human health deciphered by metabolomics

Abstract: A large variety of phytochemicals commonly consumed with the human diet, influence health and may contribute to the prevention of diseases. However, it is still difficult to make nutritional recommendations for these bioactive compounds. Current studies of phytochemicals are generally focused on specific compounds and their effects on a limited number of markers. New approaches are needed to take into account both the diversity of phytochemicals found in the diet and the complexity of their biological effects. Recent progress in high-throughput analytical technologies and in bioinformatics now allows the simultaneous analysis of the hundreds or more metabolites constituting the metabolome in urine or plasma. These analyses give complex metabolic fingerprints characteristic of a given phenotype. The exploitation of the wealth of information it contains, in randomized controlled trials and cohort studies, should lead to the discovery of new markers of intake for phytochemicals and new markers of effects. In this paper, we briefly review the current methods used to evaluate intake of phytochemicals and their effects on health. We then describe the applications of metabolomics in this field. Recent metabolomics studies illustrate the potential of such a global approach to explore the complex relationships linking phytochemical intake and metabolism and health.

Impact of food processing on the structural and allergenic properties of food allergens.

Abstract: This article reviews recent studies that address one of the major unanswered questions in food allergy research: what attributes of food or food proteins contribute to or enhance food allergenicity?

Phytochemicals in olive-leaf extracts and their antiproliferative activity against cancer and endothelial cells.

Abstract: Olive oil compounds is a dynamic research area because Mediterranean diet has been shown to protect against cardiovascular disease and cancer Olive leaves, an easily available natural material of low cost, share possibly a similar wealth of health benefiting bioactive phytochemicals In this work, we investigated the antioxidant potency and antiproliferative activity against cancer and endothelial cells of water and methanol olive leaves extracts and analyzed their content in phytochemicals using LC-MS and LC-UV-SPE-NMR hyphenated techniques Olive-leaf crude extracts were found to inhibit cell proliferation of human breast adenocarcinoma (MCF-7), human urinary bladder carcinoma (T-24) and bovine brain capillary endothelial (BBCE) The dominant compound of the extracts was oleuropein; phenols and flavonoids were also identified These phytochemicals demonstrated strong antioxidant potency and inhibited cancer and endothelial cell proliferation at low micromolar concentrations, which is significant considering their high abundance in fruits and vegetables The antiproliferative activity of crude extracts and phytochemicals against the cell lines used in this study is demonstrated for the first time

Vascular action of polyphenols

Abstract: Dietary patterns are widely recognised as contributors to cardiovascular and cerebrovascular disease. Endothelial function, the elastic properties of large arteries and the magnitude and timing of wave reflections are important determinants of cardiovascular performance. Several epidemiological studies suggest that the regular consumption of foods and beverages rich in flavonoids is associated with a reduction in the risk of several pathological conditions ranging from hypertension to coronary heart disease, stroke and dementia. The impairment of endothelial function is directly related to ageing and an association between decreased cerebral perfusion and dementia has been shown to exist. Cerebral blood flow (CBF) must be maintained to ensure a constant delivery of oxygen and glucose as well as the removal of waste products. Increasing blood flow is one potential way for improving brain function and the prospect for increasing CBF with dietary polyphenols is extremely promising. The major polyphenols shown to have some of these effects in humans are primarily from cocoa, wine, grape seed, berries, tea, tomatoes (polyphenolics and nonpolyphenolics), soy and pomegranate. There has been a significant paradigm shift in polyphenol research during the last decade. This review summarises our current knowledge in this area and points the way for the development of new types of functional foods targeted to brain health through improving vascular health.

Dietary quercetin alleviates diabetic symptoms and reduces streptozotocin-induced disturbance of hepatic gene expression in mice.

Abstract: Quercetin is a food component that may ameliorate the diabetic symptoms. We examined hepatic gene expression of BALB/c mice with streptozotocin (STZ)-induced diabetes to elucidate the mechanism of the protective effect of dietary quercetin on diabetes-associated liver injury. We fed normal and STZ-induced diabetic mice with diets containing quercetin for 2 wk and compared the patterns of hepatic gene expression in these groups of mice using a DNA microarray. Diets containing 0.1 or 0.5% quercetin lowered the STZ-induced increase in blood glucose levels and improved plasma insulin levels. A cluster analysis of the hepatic gene expressions showed that 0.5% quercetin diet suppressed STZ-induced alteration of gene expression. Gene set enrichment analysis (GSEA) and quantitative RT-PCR analysis showed that the quercetin diets had greatest suppressive effect on the STZ-induced elevation of expression of cyclin-dependent kinase inhibitor p21(WAF1/Cip1) (Cdkn1a). Quercetin also suppressed STZ-induced expression of Cdkn1a in the pancreas. Dietary quercetin might improve liver and pancreas functions by enabling the recovery of cell proliferation through the inhibition of Cdkn1a expression. Unexpectedly, in healthy control mice the 0.5 and 1% quercetin diets reduced the expression of ubiquitin C (Ubc), which has heat-shock element (HSE) in the promoter region, in the liver.

Challenging homeostasis to define biomarkers for nutrition related health

Abstract: A primary goal of nutrition research is to optimize health and prevent or delay disease. Biomarkers to quantify health optimization are needed since many if not most biomarkers are developed for diseases. Quantifying "normal homeostasis" and developing validated biomarkers are formidable tasks because of the robustness of homeostasis and of inter-individual diversity. In this paper, we discuss the science, strategies, and technologies for measuring parameters that define individual health. The following concepts are central to define the physiology of the healthy individual: (i) responses to a challenge of homeostasis will be more informative than static homeostatic measures; (ii) processes involved in maintaining homeostasis usually are multi-factorial and require quantitative analyses of the many individual components involved; (iii) health includes a large variation in "normality" and the effects of nutritional interventions may remain hidden in this "diversity of robustness," if incompletely analyzed. Specifically, comprehensive multi-parameter ("omics") analysis may identify key parameters (biomarkers) and lead to a greater understanding of health supporting processes. Perturbation tests that accurately target aspects of the overarching drivers of health (metabolism, oxidation, inflammation, and psychological stress) may be instrumental in creating knowledge for maintaining health and preventing disease through nutrition. © 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Oat β-glucan increases postprandial cholecystokinin levels, decreases insulin response and extends subjective satiety in overweight subjects

Abstract: This study recorded acute biochemical and subjective measures of satiety, followed by energy intake from a subsequent meal, after varying doses of beta-glucan in extruded breakfast cereals. Molecular weight, solubility and viscosity of beta-glucan products were determined. Seven male and seven female subjects (BMI 25-36 kg/m) consumed five breakfasts (different doses of beta-glucan sourced from two different technological processes) and dietary intake was measured after four hours. Blood was collected to measure glucose, insulin, ghrelin and cholecystokinin, and visual analogue scales measured subjective satiety. Molecular weight, solubility and viscosity indicated products were likely to increase luminal viscosity. beta-Glucan was found to decrease insulin secretion over 2 h (RMANOVA, p = 0.011) in a dose responsive manner from 2.16 to 5.68 g per serving (p = 0.007). Cholecystokinin levels increased linearly over the same range of beta-glucan concentrations (p = 0.002) in women. Subjective satiety was increased at a beta-glucan dose of 2.2 g (p = 0.039). Subsequent meal intake decreased by greater than 400 kJ with higher beta-glucan dose (>5 g). beta-Glucan improves satiety and release of cholecystokinin is likely to be part of the mechanism. Products with different sources of beta-glucan provide similar benefits but each product requires individual testing.

The bioactivity of dietary anthocyanins is likely to be mediated by their degradation products

Abstract: To date the in vitro mechanistic bioactivity of anthocyanins has been exclusively explored using aglycones and glycoside conjugates, despite a lack of evidence establishing these as the biologically available forms. We conducted intestinal epithelial cell (Caco-2 cells) culture experiments, which indicated that after a 4 h incubation of anthocyanins in cell-free culture media (DMEM), 57% of the initial cyanidin-3-glucoside (C3G) and 96% of cyanidin had degraded. The level of degradation was not statistically different from that of cultured cell incubations, suggesting that degradation was spontaneous. Degradation products were identified as protocatechuic acid (PCA) and phloroglucinaldehyde (PGA), and were confirmed in two other buffer matrices (phosphate and Hank's buffers). In cultured cell media the degradation products PCA and PGA were metabolised to glucuronide and sulphate conjugates, as indicated by both enzyme hydrolysis (sulphatase and glucuronidase treatments) and MS (PCA and PGA m/z = 155; sulphate = 235; glucuronide = 331). These data suggest a significant proportion of intestinal metabolites of anthocyanins are likely to be conjugates of their degradation products. Future efforts to establish the biological activities of anthocyanins should therefore include the investigation of phenolic acid and aldehyde products of degradation, along with their respective metabolites.

Alternariol acts as a topoisomerase poison, preferentially affecting the IIα isoform

Abstract: Alternariol (AOH), a mycotoxin formed by Alternaria alternata, has been reported to possess genotoxic properties. However, the underlying mechanism of action is unclear. Here, we tested the hypothesis that interactions with DNA-topoisomerases play a role in the DNA-damaging properties of AOH. First we compared DNA-damaging properties of AOH with other Alternaria mycotoxins such as AOH monomethyl ether (AME), altenuene and isoaltenuene. AOH and AME significantly increased the rate of DNA strand breaks in human carcinoma cells (HT29, A431) at micromolar concentrations, whereas altenuene and isoaltenuene did not affect DNA integrity up to 100 microM. Next, we selected AOH as the most DNA-damaging Alternaria metabolite for further studies of interactions with DNA topoisomerases. In cell-free assays, AOH potently inhibited DNA relaxation and stimulated DNA cleavage activities of topoisomerase I, IIalpha and IIbeta. Stabilisation of covalent topoisomerase II-DNA intermediates by AOH was also detectable in cell culture, and here, the IIalpha isoform was preferentially targeted. AOH is thus characterised as a poison of topoisomerase I and II with a certain selectivity for the IIalpha isoform. Since topoisomerase poisoning and DNA strand breakage occurred within the same concentration range, poisoning of topoisomerase I and II might at least contribute to the genotoxic properties of AOH.

Analytical and compositional aspects of isoflavones in food and their biological effects

Abstract: This paper provides an overview of analytical techniques used to determine isoflavones (IFs) in foods and biological fluids with main emphasis on sample preparation methods. Factors influencing the content of IFs in food including processing and natural variability are summarized and an insight into IF databases is given. Comparisons of dietary intake of IFs in Asian and Western populations, in special subgroups like vegetarians, vegans, and infants are made and our knowledge on their absorption, distribution, metabolism, and excretion by the human body is presented. The influences of the gut microflora, age, gender, background diet, food matrix, and the chemical nature of the IFs on the metabolism of IFs are described. Potential mechanisms by which IFs may exert their actions are reviewed, and genetic polymorphism as determinants of biological response to soy IFs is discussed. The effects of IFs on a range of health outcomes including atherosclerosis, breast, intestinal, and prostate cancers, menopausal symptoms, bone health, and cognition are reviewed on the basis of the available in vitro, in vivo animal and human data.

The anti-diabetic effect of anthocyanins in streptozotocin-induced diabetic rats through glucose transporter 4 regulation and prevention of insulin resistance and pancreatic apoptosis.

Abstract: Hyperglycemia, abnormal lipid and antioxidant profiles are the most usual complications in diabetes mellitus. Thus, in this study, we investigated the anti-diabetic and anti-oxidative effects of anthocyanins (ANT) from black soybean seed coats in streptozotocin (STZ)-induced diabetic rats. The administration of ANT markedly decreased glucose levels and improved heart hemodynamic function (left ventricular end diastolic pressure, +/-dp/dt parameters). ANT not only enhanced STZ-mediated insulin level decreases, but also decreased the triglyceride levels induced by STZ injection in serum. Diabetic rats exhibited a lower expression of glucose transporter 4 proteins in the membrane fractions of heart and skeletal muscle tissues, which was enhanced by ANT. In addition, ANT activated insulin receptor phosphorylation, suggesting an increased utilization of glucose by tissues. Moreover, ANT protected pancreatic tissue from STZ-induced apoptosis through regulation of caspase-3, Bax, and Bcl-2 proteins. Furthermore, ANT significantly suppressed malondialdehyde levels and restored superoxide dismutase and catalase activities in diabetic rats. Interestingly, the observed effects of ANT were superior to those of glibenclamide. Taken together, ANT from black soybean seed coat have anti-diabetic effects that are due, in part, to the regulation of glucose transporter 4 and prevention of insulin resistance and pancreatic apoptosis, suggesting a possible use as a drug to regulate diabetes.

Monodemethylated polymethoxyflavones from sweet orange (Citrus sinensis) peel Inhibit growth of human lung cancer cells by apoptosis

Abstract: Polymethoxyflavones (PMFs) are almost exclusively found in the Citrus genus, particularly in the peels of sweet orange (Citrus sinensis L. Osbeck) and mandarin (C. reticulate Blanco). We studied the effects of two major PMFs, namely, nobiletin and 3,5,6,7,8,3',4'-heptamethoxyflavone (HMF), and two major monodemethylated PMFs, namely 5-hydroxy-3,7,8,3',4'-pentamethoxyflavone (5HPMF), and 5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone (5HHMF), on the growth of human lung cancer H1299, H441, and H460 cells. Monodemethylated PMFs were much more potent in growth inhibition of lung cancer cells than their permethoxylated counterpart PMFs. In H1299 cells, cell cycle analyses further revealed that monodemethylated PMFs caused significant increase in sub-G0/G1 phase, suggesting possible role of apoptosis in the growth inhibition observed, whereas the permethoxylated counterpart PMFs did not affect cell cycle distribution at same concentrations tested. These results strongly suggested that the phenolic group is essential for the growth inhibitory activity of monodemethylated PMFs. Further studies in H1299 cells demonstrated that monodemethylated PMFs downregulated oncogenic proteins, such as iNOS, COX-2, Mcl-1, and K-ras, as well as induced apoptosis evidenced by activation of caspase-3 and cleavage of PARP. Our results provide rationale to develop orange peel extract enriched with monodemethylated PMFs into value-added nutraceutical products for cancer prevention.

Anti‐obese property of fucoxanthin is partly mediated by altering lipid‐regulating enzymes and uncoupling proteins of visceral adipose tissue in mice

Abstract: This study investigated the anti-obesity effects of fucoxanthin in diet-induced obesity mice fed a high-fat diet (20% fat, wt/wt). The mice were supplemented with two doses of fucoxanthin (0.05 and 0.2%, wt/wt) for 6 wk. Fucoxanthin significantly lowered body weight and visceral fat-pads weights compared with the control group without altering food intake. In epididymal adipose tissue of fucoxanthin-fed mice, adipocyte sizes and mRNA expression of lipogenic and fatty acid beta-oxidation enzymes were significantly altered in a dose-dependent manner. Plasma leptin level was significantly lower in the fucoxanthin groups than in the control group, while the adiponectin level was elevated. Fucoxanthin significantly down-regulated various lipogenic enzyme activities in epididymal adipose tissue with a simultaneous decrease in fatty acid beta-oxidation activity. The 0.2% fucoxanthin supplement led to increase mRNA expression of uncoupling protein-1 (UCP-1) and UCP-3 in brown adipose tissue and that of UCP-2 in the epididymal white adipose tissue. However, the 0.05% fucoxanthin only elevated UCP-1 mRNA expression in epididymal white adipose tissue. These results suggest that the anti-obesity effect of fucoxanthin could be mediated by altering lipid-regulating enzymes and UCPs in the visceral fat tissues and plasma adipokine levels.

Influence of postharvest processing and storage on the content of phenolic acids and flavonoids in foods.

Abstract: The review is based on the evaluation of electronically collated data published between 2002 to June 2006. It is based on 325 references dealing with the following subclasses of phenolic compounds: hydroxycinnamic and hydroxybenzoic acids, chalcones, flavanones, flavones, flavonols, monomeric flavanols and anthocyanins. Only publications dealing directly with the effects of storage and postharvest processing on the phenolic acid and flavonoid contents of foods were considered. The expectation that the structural diversity even within each subgroup, and the number of different procedures and of different parameters would make finding homogenous tendencies unlikely, has, in most instances, been confirmed. By adding a database Excel table combined with a focused and unified evaluation, specific additional information was rendered accessible and concise. It holds true for most of the subclasses in question that the effect of storage and food processing on the polyphenol content is negligible in comparison to the differences between different varieties of plants. Variety dependence must always be considered, for all classes of compounds.

Purified berry anthocyanins but not whole berries normalize lipid parameters in mice fed an obesogenic high fat diet

Abstract: Male C57BL/6 mice received diets with either 10% of kcal from fat, or a high fat diet [45% (HF45) or 60% (HF60) kcal from fat]. Diets were prepared with or without freeze-dried powders (10%) from whole blueberries (BB), strawberries (SB), Concord grape or black raspberry. In the 2nd study, purified anthocyanins (ACNs) from SB or BB were added to the drinking water of the treatments fed the HF60 diet. In Study 1, serum triglycerides were increased by feeding the HF45 diet but were elevated further when black raspberry or BB was included in the HF45 diet. Liver total lipids and triglycerides were increased in mice fed HF45 diet and inclusion of any of the berry powders in the HF45 diet did not alter concentrations compared to HF45 controls. In the 2nd study, mice fed the HF60 diet plus purified ACNs from BB in the water had lower body weight gains and body fat than the HF60 fed. Serum cholesterol and triglyceride levels were elevated with the HF60 diet and decreased to control levels when ACNs from either SB or BB were included in the drinking water. Serum leptin levels were consistently decreased to control low fat levels in those ACN treatments in which measures of body fat were decreased. Administering purified ACNs from BB and strawberry via drinking water prevented the development of dyslipidemia and obesity in mice, but feeding diets containing whole berries or purple corn (PC) ACNs did not alter the development of obesity.

Influence of apple polyphenols on inflammatory gene expression

Abstract: Apples (Malus spp., Rosaceae) and products thereof contain high amounts of polyphenols which show diverse biological activities and may contribute to beneficial health effects, like protecting the intestine against inflammation initiated by chronic inflammatory bowel diseases (IBD). IBD are characterized by an excessive release of several proinflammatory cytokines and chemokines by different cell types which results consequently in an increased inflammatory response. In the present study we investigated the preventive effectiveness of polyphenolic juice extracts and single major constituents on inflammatory gene expression in immunorelevant human cell lines (DLD-1, T84, MonoMac6, Jurkat) induced with specific stimuli. Besides the influence on proinflammatory gene expression, the effect on NF-kappaB-, IP-10-, IL-8-promoter-, STAT1-dependent signal transduction, and the relative protein levels of multiple released cytokines and chemokines were studied. DNA microarray analysis of several genes known to be strongly regulated during gastrointestinal inflammation, combined with quantitative real-time PCR (qRT-PCR) revealed that the apple juice extract AE04 (100-200 microg/mL) significantly inhibited the expression of NF-kappaB regulated proinflammatory genes (TNF-alpha, IL-1beta, CXCL9, CXCL10), inflammatory relevant enzymes (COX-2, CYP3A4), and transcription factors (STAT1, IRF1) in LPS/IFN-gamma stimulated MonoMac6 cells without significant effects on the expression of house-keeping genes. A screening of some major compounds of AE04 revealed that the flavan-3-ol dimer procyanidin B(2 )is mainly responsible for the anti-inflammatory activity of AE04. Furthermore, the dihydrochalcone aglycone phloretin and the dimeric flavan-3-ol procyanidin B(1 )significantly inhibited proinflammatory gene expression and repressed NF-kappaB-, IP-10-, IL-8-promoter-, and STAT1-dependent signal transduction in a dose-dependent manner. The influence on proinflammatory gene expression by the applied polyphenols thereby strongly correlated with the increased protein levels investigated by human cytokine array studies. In summary, we evaluated selected compounds responsible for the anti-inflammatory activity of AE04. In particular, procyanidin B(1), procyanidin B(2), and phloretin revealed anti-inflammatory activities in vitro and therefore may serve as transcription-based inhibitors of proinflammatory gene expression.

Gene expression, cell cycle arrest and MAPK signalling regulation in Caco-2 cells exposed to ellagic acid and its metabolites, urolithins

Abstract: Novel gene expression profiles and cellular functions modulated in Caco-2 cells in response to the dietary polyphenol, ellagic acid (EA), and its colonic metabolites, urolithin-A (3,8-dihydroxy-6H-dibenzo[b,d] pyran-6-one) and urolithin-B (3-hydroxy-6H-dibenzo[b,d] pyran-6-one) have been identified. Exposure of cells to EA and urolithins arrested cell growth at the S- and G(2)/M-phases. Transcriptional profiling using microarray and functional analysis revealed changes in the expression levels of MAPK signalling genes such as, growth factor receptors (FGFR2, EGFR), oncogenes (K-Ras, c-Myc), and tumour suppressors (DUSP6, Fos) and of genes involved in cell cycle (CCNB1, CCNB1IP1). Results suggest that EA and urolithin-A and -B, at concentrations achievable in the lumen from the diet, might contribute to colon cancer prevention by modulating the expression of multiple genes in epithelial cells lining the colon. Some of these genes are involved in key cellular processes associated with cancer development and are currently being investigated as potential chemopreventive targets.

Absorption of anthocyanins through intestinal epithelial cells - Putative involvement of GLUT2.

Abstract: Anthocyanins bioavailability is a major issue regarding their biological effects and remains unclear due to few data available on this matter. This work aimed to evaluate the absorption of anthocyanins at the intestine using Caco-2 cells. Anthocyanin extract, rich in malvidin-3-glucoside, was obtained from red grape skins and tested on Caco-2 cells. The absorption of anthocyanins, in absence or presence of 1% ethanol, was detected by HPLC/DAD/LC-MS. Our results showed that this transport was significantly increased in the presence of ethanol especially after 60 min of incubation. In addition, cells that were pretreated for 96 h with anthocyanins (200 microg/mL) showed an increase of their own transport (about 50% increase). Expression of glucose transporters sodium-dependent glucose transporter 1, facilitative glucose transporters 5, and facilitative glucose transporters 2 was assessed by RT-PCR. It was found that facilitative glucose transporters 2 expression was increased (60%) in Caco-2 cells pretreated with anthocyanins, by comparison with controls. When the effect of anthocyanin extract on (3)H-2-deoxy-D-glucose uptake was tested, an inhibitory effect was observed (about 60% decrease). However, the malvidin aglycone was tested and had no effect. In conclusion, anthocyanins could be absorbed through Caco-2 cells, and can interfere with their own transport and also with glucose intestinal uptake.