Hill coefficients of dietary polyphenolic enzyme inhibitiors: can beneficial health effects of dietary polyphenols be explained by allosteric enzyme denaturing?

Inspired by a recent article by Prinz, suggesting that Hill coefficients, obtained from four parameter logistic fits to dose–response curves, represent a parameter allowing distinction between a general allosteric denaturing process and real single site enzyme inhibition, Hill coefficients of a number of selected dietary polyphenol enzyme inhibitions were compiled from the available literature. From available literature data, it is apparent that the majority of polyphenol enzyme interactions reported lead to enzyme inhibition via allosteric denaturing rather than single site inhibition as judged by their reported Hill coefficients. The results of these searches are presented and their implications discussed leading to the suggestion of a novel hypothesis for polyphenol biological activity termed the insect swarm hypothesis.     

The effects of dietary consumption of plants secondary compounds on small ruminants’ products quality

Worldwide policies are encouraging the use of natural rangelands and low input feeding resources for livestock farming. Most of the low input feed contain secondary compounds (PSCs) – such as phenolic compounds (PhCs), saponins, and essential oils (EO) – which play a primary role on animal digestion and performances and also on product quality. Meat and milk fatty acid composition can be manipulated by dietary tannins as these PSCs modify ruminal biohydrogenation of dietary polyunsaturated fatty acids through changes in ruminal ecology. Dietary tannins improve products’ flavour by reducing the ruminal biosynthesis of skatole and its accumulation in meat and milk. The addition of garlic or juniper EO in lamb diets reduces the off-flavours perception while thyme or rosemary EO lowered the rancid-odour perception of meat under display. It is proved that dietary PhCs ameliorate meat oxidative stability and prevent meat from discoloration thus extending product shelf life. The dose–response effect of these PSCs as well as their mechanisms of action are not fully unravelled. Nevertheless, the use of plants rich in secondary compounds or the supplementation of purified PSCs in small ruminants diet seem to be a promising strategy for improving products quality.     

Gut sensing of dietary K⁺ intake increases renal K⁺excretion

Dietary K(+) intake may increase renal K(+) excretion via increasing plasma [K(+)] and/or activating a mechanism independent of plasma [K(+)]. We evaluated these mechanisms during normal dietary K(+) intake. After an overnight fast, [K(+)] and renal K(+) excretion were measured in rats fed either 0% K(+) or the normal 1% K(+) diet. In a third group, rats were fed with the 0% K(+) diet, and KCl was infused to match plasma [K(+)] profile to that of the 1% K(+) diet group. The 1% K(+) feeding significantly increased renal K(+) excretion, associated with slight increases in plasma [K(+)], whereas the 0% K(+) diet decreased K(+) excretion, associated with decreases in plasma [K(+)]. In the KCl-infused 0% K(+) diet group, renal K(+) excretion was significantly less than that of the 1% K(+) group, despite matched plasma [K(+)] profiles. We also examined whether dietary K(+) alters plasma profiles of gut peptides, such as guanylin, uroguanylin, glucagon-like peptide 1, and glucose-dependent insulinotropic polypeptide, pituitary peptides, such as AVP, α-MSH, and γ-MSH, or aldosterone. Our data do not support a role for these hormones in the stimulation of renal K(+) excretion during normal K(+) intake. In conclusion, postprandial increases in renal K(+) excretion cannot be fully accounted for by changes in plasma [K(+)] and that gut sensing of dietary K(+) is an important component of the regulation of renal K(+) excretion. Our studies on gut and pituitary peptide hormones suggest that there may be previously unknown humoral factors that stimulate renal K(+) excretion during dietary K(+) intake.     

The α-linolenic acid content of flaxseed can prevent the atherogenic effects of dietary trans fat

Dietary intake of industrially hydrogenated trans fatty acids (TFA) has been associated with coronary heart disease. Dietary flaxseed can inhibit atherosclerosis induced by dietary cholesterol. The aim of this study was to determine whether supplementing the diet with flaxseed could protect against atherosclerosis induced by a diet enriched in TFA. Low-density lipoprotein receptor-deficient (LDLr(-/-)) mice were fed 1 of 14 experimental diets for 14 wk containing one of two fat sources [regular (pork/soy) or trans fat] at two concentrations (4 or 8%) and supplemented with or without dietary cholesterol (2%), whole ground flaxseed, or one of the components of flaxseed [α-linolenic acid (ALA), defatted fiber, or lignan]. Adding flaxseed to the diet partially mitigated the rise in circulating cholesterol levels induced by the cholesterol-enriched diet. Atherosclerosis was stimulated by TFA and/or cholesterol. Including milled flaxseed to an atherogenic diet significantly reduced atherosclerosis compared with the groups that consumed cholesterol and/or TFA. ALA was the only component within flaxseed that could inhibit the atherogenic action of cholesterol and/or TFA on its own. Dietary flaxseed protects against atherosclerotic development induced by TFA and cholesterol feeding through its content of ALA.     

Dieback of rural eucalypts: Does insect herbivory relate to dietary quality of tree foliage?

Foliar dietary quality, and the damage that insects caused to the foliage of dieback-affected and healthy Eucalyptus blakelyi trees, were monitored for 3 years, on pastoral properties in the Australian Capital Territory. Compared with healthy trees, the foliage of dieback trees was more heavily grazed by insects, and its dietary quality was generally superior. Some of the differences in dietary quality were related to the average age of the foliage of healthy and dieback trees. But when statistical models were used to equalize the effects of differences in leaf ages, leaves on dieback trees nonetheless tended to have lower specific weights, and were sometimes rounder and contained more nitrogen. Regression analyses of herbivory against each of the dietary quality variables showed that the only significant relationship that was consistent for both of the years monitored was for foliar nitrogen and herbivory for both dieback and healthy trees. In the first year, regressions between herbivory and specific leaf weight, shape, or sugar content were also significant, but only amongst the dieback trees. This may indicate that these relationships were a response to, rather than a primary cause of, the repeated high defoliation of the dieback trees. Multiple regression equations incorporating annual means of several quality variables explained a high proportion of the variance in annual herbivory, but were grossly different between years.     

Inhibition of polypeptide N-acetyl-α-galactosaminyltransferases is an underlying mechanism of dietary polyphenols preventing colorectal tumorigenesis

Ellagitannin-derived ellagic acid (EA) and colonic metabolite urolithins are functional dietary ingredients for cancer prevention, but the underlying mechanism need elucidation. Mucin-type O-glycosylation, initiated by polypeptide N-acetyl-α-galactosaminyltransferases (ppGalNAc-Ts), fine-tunes multiple biological processes and is closely associated with cancer progression. Herein, we aim to explore how specific tannin-based polyphenols affect tumor behavior of colorectal cancer cells (CRC) by modulating O-glycosylation. Utilizing HPLC-based enzyme assay, we find urolithin D (UroD), EA and gallic acid (GA) potently inhibit ppGalNAc-Ts. In particular, UroD inhibits ppGalNAc-T2 through a peptide/protein-competitive manner with nanomolar affinity. Computational simulations combined with site-directed mutagenesis further support the inhibitors’ mode of action. Moreover, lectin analysis and metabolic labelling reveal that UroD can reduce cell O-glycans but not N-glycans. Transwell experiments prove that UroD inhibits migration and invasion of CRC cells. Our work proves that specific tannin-based polyphenols can potently inhibit ppGalNAc-Ts activity to reduce cell O-glycosylation and lead to lowering the migration and invasion of CRC cells, suggesting that disturbance of mucin-type O-glycosylation is an important mechanism for the function of dietary polyphenols.     

Modulation of in vitro activity of zymogenic and mature recombinant human β-secretase by dietary plants

The in vitro activity of human recombinant β-secretase (BACE1) was studied using a fluorogenic substrate based on the cleavage site for the enzyme in the Swedish mutation of amyloid precursor protein. The enzyme was inhibited by a control peptide inhibitor with good repeatability. The enzyme preparation comprised a mixture of pro-enzyme or zymogen and mature enzyme whereby the pro-enzyme sequence forms a 'flap' that can obstruct the binding site. 'Open flap' forms of the zymogen and mature enzyme are active, but the 'closed flap' form of the zymogen is inactive. This mixture of enzyme populations permitted apparent stimulation of enzyme activity under particular conditions, presumably due to facilitating flap-opening of the zymogen. As reported for heparin, enzyme activation was stimulated in the presence of low concentrations of Tween 20 and dimethylsulfoxide before becoming inhibited at higher concentrations. Dietary plant extracts either consistently inhibited (e.g. clove, tea, cinammon) or consistently stimulated (e.g. mushroom, parsley, asparagus) BACE1. Common structural features identified by Fourier transform infrared spectroscopy revealed that BACE1 activity could be explained by differential interactions of either small molecule or polymeric species with mature versus zymogen forms of the enzyme, respectively. Further, enzyme activity could be reversed by mixtures of high and low mass species. These results may have implications for the regulation of β-secretase activity in vivo by either endogenous or possibly dietary factors and for a potential role of BACE1 in stimulation of the production of amyloid beta peptide in sporadic Alzheimer's disease.     

The effect of vitamin A deficiency and dietary α-tocopherol on the stability of rat-liver lysosomes

1. Vitamin A-deficient rats and pair-fed controls were maintained on either normal or raised amounts of dietary alpha-tocopherol. 2. Their livers were fractionated and ;free' and ;total' lysosomal phosphatase were determined in the various fractions. The rate of release of this enzyme was determined in the mitochondria-lysosome-rich fraction during incubation at pH5 and 37 degrees . 3. The deficient livers showed increased enzymic activity. 4. Prolonged incubation caused more rapid enzyme release from the mitochondria-lysosome-rich fraction of the vitamin A-deficient rats receiving the normal amount of dietary alpha-tocopherol than from the equivalent fraction of their pair-fed controls receiving vitamin A. Raised dietary alpha-tocopherol reversed this phenomenon.     

Effect of high levels of dietary vitamin C on the blood responses of matrinxã (Brycon amazonicus)

Juvenile matrinx? (Brycon amazonicus) were fed with different dietary vitamin C (ascorbic acid or AA) concentrations for 2 months in order to evaluate its effect on the physiological condition of this species. Five treatments were tested: Reference diet-RD (350 mg AA kg(-1) and 45% crude protein commercial feed); C400, C500, C600 and C800 with supplementation of 400, 500, 600 and 800 mg AA kg(-1). Fish fed 800 mg AA kg(-1) supplemented diets presented greater weight gain and survival. Hematocrit, hemoglobin concentrations and erythrocytes showed significant increase (p<0.05) in C600 and C800 relatively to the others. Total leukocyte values were significantly higher in fish fed vitamin C supplemented diets relatively to those fed RD and leukocytes count of C600 and C800 were the highest among the treatments. Monocytes were the only cells of fish defense mechanism that presented variation, and C600 and C800 presented the lowest values (P<0.05). Glucose level was significantly different relatively to RD only in C400 and the plasmatic total protein values for fish fed vitamin C supplemented diets were higher than for fish fed the RD. Fish plasmatic ions (Na(+) and Cl(-)) were significantly lower for C500, C600 and C800 relatively to C400 and RD. The physiological profile and the growth performance of matrinx? suggest that diet supplemented with 800 mg AA kg(-1) can improve its performance and increase the survival rate.     

Are metals dietary carcinogens?

Humans have been in contact with metals almost since the beginning of our existence. In fact, one cannot even think on human evolution without considering the great role played by metals in mankind's development. Metals are common moieties of molecules involved in a wide variety of biological processes, and hence are found in virtually all living organisms. Some metals are essential for human nutrition; others are found as contaminants in foodstuffs. One feature of the normal human diet which is frequently found is the simultaneous presence of both essential and toxic metals. Other factors important in the risk-evaluation analysis of metals are their pharmacokinetics, interactions among them and with other major components of the diet, and, especially, the great differences in the dietary habits of different populations and in the regional distribution of metals. In attempting to understand the role which dietary metals could play in human carcinogenesis, we found that the many factors involved and the lack of specific information made it difficult to reach firm conclusions on the hazards of dietary metals. We hope that this paper will raise the interest of genetic toxicologists in the subject and will consequently facilitate a risk analysis of the carcinogenic potential of dietary metals.     

Protective effects of dietary EPA and DHA on ischemia–reperfusion-induced intestinal stress

The immunoregulatory effects of dietary omega-3 fatty acids are still not fully characterized. The aim of this study was to determine whether dietary eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intake limits intestinal ischemia–reperfusion (IR) injury. To test this, rats were fed either control or EPA/DHA supplemented diet for 3 weeks following which they underwent either a sham or an IR surgical protocol. A significant reduction in mucosal damage was observed after EPA/DHA supplemented diet as reflected by maintenance of total protein content. To address the underlying mechanisms of protection, we measured parameters of oxidative stress, intestinal and serological cytokines and intestinal eicosanoids. Interestingly, EPA/DHA fed animals displayed a higher activity of oxidative stress enzyme machinery, i.e., superoxide dismutase and catalase in addition to a reduction in total nitrate/nitrite content. While no changes in cytokines were observed, eicosanoid analyses of intestinal tissue revealed an increase in metabolites of the 12-lipoxygenase pathway following IR. Further, IR in EPA/DHA fed animals was accompanied by a significant increase of 17,18-epoxyeicosatetraenoic acid, 8-Iso prostaglandin F_3α and thromboxane B₃, by more than 12-, 6-, 3-fold, respectively. Thus, the data indicate that EPA/DHA supplementation may be able to reduce early intestinal IR injury by anti-oxidative and anti-inflammatory mechanisms.     

Lygus hesperus （Heteroptera： Miridae） tolerates high concentrations of dietary nickel

Nickel hyperaccumulator plants contain unusually elevated levels of Ni （〉 1 000 μg Ni/g）. Some insect herbivores, including Lygus hesperus （Western tarnished plant bug）, have been observed feeding on the California Ni hyperaccumulator Streptanthus polygaloides. This bug may be able to utilize S. polygaloides as a host either through its feeding behavior or by physiological tolerance of Ni. This experiment determined the Ni tolerance of L hesperus by offering insects artificial diet amended with 0, 0.4, 1, 2, 4.5, 10, 20 and 40 mmol Ni/L and recording survival. Survival varied due to Ni concentration, with diets containing 10 mmol Ni/L and greater resulting in significantly lower survival compared to the control （0 mmol Ni/L） treatment. Insects tolerated diet containing as much as 4.5 mmol Ni/L, a relatively elevated Ni concentration. I conclude that L hesperus can feed on S. polygaloides because it is Ni-tolerant, probably due to physiological mechanisms that provide it with resistance to plant chemical defenses including elemental defenses such as hyperaccumulated Ni.     

Relation between age–sex classes and dietary selection of wild Japanese monkeys

Dietary selection by wild Japanese monkeys (Macaca fuscata yakui Kuroda) was examined in relation to body size. The monkeys were classified into three age–sex categories: adult males, adult females and immatures excluding suckling infants. Time spent feeding did not differ between age–sex classes, although time spent moving was longer in lighter classes. Heavier individuals fed relatively more on mature leaves, while lighter individuals fed on insects more frequently. Mature leaves were more abundant but had lower energy content than other food items in the forest. Heavier monkeys seemed to feed on greater amounts of lower quality food in this species. This finding agrees with the Jarman–Bell principle on ungulates.     

Evolution of the response patterns to dietary carbohydrates and the developmental differentiation of gene expression of α-amylase in Drosophila

Intraspecific variation of -amylase activity in D. melanogaster and D. immigrans, which is distantly related to D. melanogaster, and interspecific variation of -amylase activity in 18 Drosophila species were examined. The amount of intraspecific variation of -amylase activities measured in terms of coefficient of variation in D. melanogaster and D. immigrans was one-half and one-tenth or less, respectively, of the interspecific variation in 18 Drosophila species. We also surveyed the response patterns of -amylase activity to dietary carbohydrates at the larval and adult stages. The levels of -amylase activity depended on both repression by dietary glucose (glucose repression) and induction by dietary starch (starch induction). In general, our data suggest that glucose repression was conserved among species at both stages while starch induction was mainly observed in larvae, although the degree of the response depended on species. In D. lebanonensis lebanonensis and D. serrata, larvae expressed electrophoretically different -amylase variants (isozymes) from those of adult flies. These results may suggest that the regulatory systems responsible both for the response to environment and developmental expression are different among species in Drosophila. Correspondence to: T. Yamazaki     

The daily dietary intake of ochratoxin a — Results of a duplicate portion study with Bavarian schoolchildren

The daily dietary intakes of ochratoxin A (OTA) were estimated for 28 school-children at the age of seven and eight years using duplicate portions of the total diets collected on three successive days. For most children and collection days the dietary OTA intakes were below the PTDI-value of 5 ng/kg bw/day. The mean dietary intake was 1.52 ng/kg bw/day for all children. According to sex the mean intakes were 1.21 ng/kg bw/day for boys and 1.83 ng/kg bw/day for girls.