Chlorogenic acid and its metabolite m-coumaric acid evoke neurite outgrowth in hippocampal neuronal cells

We evaluated the neurotrophic activity of dietary polyphenols by using primary cultures of fetal rat hippocampal neurons in a serum-free medium. Among the tested compounds, chlorogenic acid and its metabolite, m-coumaric acid, together with catechins and flavanone, were found to promote neuronal differentiation comparable to the phytochemical, honokiol, which has been reported to show potent neurotrophic activity. The present findings may contribute to the development of further neurotrophic studies on dietary polyphenols and their metabolites.     

Simple high-performance liquid chromatographic method for assaying cysteinesulfinic acid decarboxylase activity in rat tissue

A simple method is described for determining cysteinesulfinic acid decarboxylase activity in rat tissue. Enzyme preparations from the liver, kidney and brain were incubated with cysteinesulfinic acid substrate in the presence of pyridoxal 5-phosphate. The enzyme product, hypotaurine, was derivatized with o-phthalaldehyde and separated by reversed-phase high-performance liquid chromatography (Capsel Pack AG 120A C₁₈ column) using a mobile phase of acetonitrile–water (20:80, v/v) containing 50 mM sodium phosphate buffer (pH 6.0) and detected using a fluorometer (excitation at 360 nm and emission at 455 nm). The method described is reproducible and sensitive enough to determine the activity of cysteinesulfinic acid decarboxylase activity in the liver, kidney and brain. This assay was subsequently used to evaluate the effect of dietary proteins whose sulfur amino acid contents differ. Consistent with reported data, compared to casein and whole egg protein, a dietary protein low in sulfur amino acid (soybean protein) increased cysteinesulfinic acid decarboxylase activity in the liver and kidney. This method is therefore applicable to studies on the dietary regulation of cysteinesulfinic acid decarboxylase in rat tissue.     

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.     

Enhancement of antibacterial effects of epigallocatechin gallate, using ascorbic acid

Although plant polyphenols such as (−)-epigallocatechin gallate (EGCG) have antibacterial activity towards methicillin-resistant Staphylococcus aureus (MRSA), such polyphenols are unstable in solution. Because the instability of polyphenols is attributable to their oxidation, we examined the effects of antioxidants and inhibitors of polyphenol oxidation on the maintenance of polyphenol antibacterial activity. The antibacterial activity of EGCG was enhanced in the presence of ascorbic acid, and ascorbic acid was the most effective for retaining the concentration of stable EGCG. On the other hand, the antibacterial activity of EGCG was lowered in the presence of casein in spite of its suppressing effect on the EGCG decrease. The effect of EGCG on the antibiotic resistance of MRSA was also enhanced in the presence of ascorbic acid. The addition of an antioxidant may affect other pharmacological effects of polyphenols in analogous ways, although this does not mean the clinical usefulness of the addition directly.     

Dietary linolenic acid and fasting glucose and insulin: the National Heart, Lung, and Blood Institute Family Heart Study

Objective: To assess whether dietary linolenic acid is associated with fasting insulin and glucose. Research Methods and Procedures: In a cross‐sectional design, we studied 3993 non‐diabetic participants of the National Heart, Lung, and Blood Institute Family Heart Study 25 to 93 years of age. Linolenic acid was assessed through a food frequency questionnaire, and laboratory data were obtained after at least a 12‐hour fast. We used generalized linear models to calculate adjusted means of insulin and glucose across quartiles of dietary linolenic acid. Results: From the lowest to the highest sex‐specific quartile of dietary linolenic acid, means ± standard error for logarithmic transformed fasting insulin were 4.06 ± 0.02 (reference), 4.09 ± 0.02, 4.13 ± 0.02, and 4.17 ± 0.02 pM, respectively (trend, p < 0.0001), after adjustment for age, sex, energy intake, waist‐to‐hip ratio, smoking, and high‐density lipoprotein‐cholesterol. When dietary linolenic acid was used as a continuous variable, the multivariable adjusted regression coefficient was 0.42 ± 0.08. There was no association between dietary linolenic acid and fasting glucose (trend p = 0.82). Discussion: Our data suggest that higher consumption of dietary linolenic acid is associated with higher plasma insulin, but not glucose levels, in non‐diabetic subjects. Additional studies are needed to assess whether higher intake of linolenic acid results in an increased insulin secretion and improved glucose use in vivo.     

Dietary fatty acids promote sleep through a taste‐independent mechanism

Consumption of foods that are high in fat contribute to obesity and metabolism‐related disorders. Dietary lipids are comprised of triglycerides and fatty acids, and the highly palatable taste of dietary fatty acids promotes food consumption, activates reward centers in mammals and underlies hedonic feeding. Despite the central role of dietary fats in the regulation of food intake and the etiology of metabolic diseases, little is known about how fat consumption regulates sleep. The fruit fly, Drosophila melanogaster, provides a powerful model system for the study of sleep and metabolic traits, and flies potently regulate sleep in accordance with food availability. To investigate the effects of dietary fats on sleep regulation, we have supplemented fatty acids into the diet of Drosophila and measured their effects on sleep and activity. We found that flies fed a diet of hexanoic acid, a medium‐chain fatty acid that is a by‐product of yeast fermentation, slept more than flies starved on an agar diet. To assess whether dietary fatty acids regulate sleep through the taste system, we assessed sleep in flies with a mutation in the hexanoic acid receptor Ionotropic receptor 56D, which is required for fatty acid taste perception. We found that these flies also sleep more than agar‐fed flies when fed a hexanoic acid diet, suggesting the sleep promoting effect of hexanoic acid is not dependent on sensory perception. Taken together, these findings provide a platform to investigate the molecular and neural basis for fatty acid‐dependent modulation of sleep.     

Dietary polyphenols in chemoprevention and synergistic effect in cancer: Clinical evidences and molecular mechanisms of action

BackgroundEpidemiological studies has revealed that a diet rich in fruits and vegetables could lower the risk of certain cancers. In this setting, natural polyphenols are potent anticancer bioactive compounds to overcome the non-target specificity, undesirable cytotoxicity and high cost of treatment cancer chemotherapy.PurposeThe review focuses on diverse classifications of the chemical diversity of dietary polyphenol and their molecular targets, modes of action, as well as preclinical and clinical applications in cancer prevention.ResultsThe dietary polyphenols exhibit chemo-preventive activity through modulation of apoptosis, autophagy, cell cycle progression, inflammation, invasion and metastasis. Polyphenols possess strong antioxidant activity and control multiple molecular events through activation of tumor suppressor genes and inhibition of oncogenes involved in carcinogenesis. Numerous in vitro and in vivo studies have evidenced that these dietary phytochemicals regulate critical molecular targets and pathways to limit cancer initiation and progression. Moreover, natural polyphenols act synergistically with existing clinically approved drugs. The improved anticancer activity of combinations of polyphenols and anticancer drugs represents a promising perspective for clinical applications against many human cancers.ConclusionThe anticancer properties exhibited by dietary polyphenols are mainly attributed to their anti-metastatic, anti-proliferative, anti-angiogenic, anti-inflammatory, cell cycle arrest, apoptotic and autophagic effects. Hence, regular consumption of dietary polyphenols as food or food additives or adjuvants can be a promising tactic to preclude adjournment or cancer therapy.     

Dietary management and physical exercise can improve climbing defects and mitochondrial activity in Drosophila melanogaster parkin null mutants

Physical exercise can improve gait, balance, tremor, flexibility, grip strength and motor coordination in Parkinson’s disease (PD) patients. Several lines of evidence have also shown the therapeutic potential of dietary management and supplementation in halting the progression of PD. However, there is a lack of research on the combined effects of physical activity and nutrition in the progression of PD. We test the effects exercise and dietary modification in a Drosophila model of PD. In this study, we fed Drosophila parkin mutants high protein and high carbohydrate diets without and with stearic acid (4 treatments in total). In parallel, we subjected mutants to a regimen of exercise using a purpose-built ‘Power tower’ exercise machine. We then measured climbing ability, aconitase activity, and basal mitochondrial ROS levels. We observed that exercising parkin mutants fed the high protein diet improved their climbing ability and increased aconitase activity. There was an additional improvement in climbing and aconitase activity in exercised parkin mutants fed the high protein diet supplemented with stearic acid. No benefits of exercise were seen in parkin mutants fed the high carbohydrate diet. Combined, these results suggest that dietary management along with physical activty has potential to improve mitochondrial biogenesis and delay the progression of PD in Drosophila parkin mutants.     

Alpha-linolenic acid and its conversion to longer chain n−3 fatty acids: Benefits for human health and a role in maintaining tissue n−3 fatty acid levels

There is little doubt regarding the essential nature of alpha-linolenic acid (ALA), yet the capacity of dietary ALA to maintain adequate tissue levels of long chain n−3 fatty acids remains quite controversial. This simple point remains highly debated despite evidence that removal of dietary ALA promotes n−3 fatty acid inadequacy, including that of docosahexaenoic acid (DHA), and that many experiments demonstrate that dietary inclusion of ALA raises n−3 tissue fatty acid content, including DHA. Herein we propose, based upon our previous work and that of others, that ALA is elongated and desaturated in a tissue-dependent manner. One important concept is to recognize that ALA, like many other fatty acids, rapidly undergoes β-oxidation and that the carbons are conserved and reused for synthesis of other products including cholesterol and fatty acids. This process and the differences between utilization of dietary DHA or liver-derived DHA as compared to ALA have led to the dogma that ALA is not a useful fatty acid for maintaining tissue long chain n−3 fatty acids, including DHA. Herein, we propose that indeed dietary ALA is a crucial dietary source of n−3 fatty acids and its dietary inclusion is critical for maintaining tissue long chain n−3 levels.     

Vochysiaceae: secondary metabolites, ethnopharmacology and pharmacological potential

Many Vochysiaceae species, in special Qualea and Vochysia genera, are widely used in folk medicine to treat several diseases. This review describes some aspects of their ethnopharmacology potential, biological activity and the secondary metabolites reported so far for Vochysiaceae. The chemical constituents of this family include triterpenoids, steroids and polyphenols like flavonoids and ellagic acid derivatives.     

Investigation of the mechanisms affecting Cu and Fe bioavailability from legumes

Chemical composition and content in polyphenols, phytic acid, and dietary fiber of whole cooked common bean (Phaseolus vulgaris L.) and faba bean (Vicia faba L.) and of soluble and insoluble fractions separated from them were determined. Simultaneous determination of Cu, Fe, and protein bioavailability in the small intestine of rat was carried out in single-dose, short-term (1 h) experiments. After cooking, about 80% of seed components (on a weight basis) of either legume was recovered in the precipitate (insoluble fraction) after extraction with water. Protein, lipid, starch, dietary fiber, and polyphenols underwent the most severe insolubilization, together with more than 70% of total Cu and Fe. Cu, Fe, and protein bioavailability showed a similar trend (i.e., the lower the protein, the lower the Cu and Fe availability). Availability of proteins, Cu, and Fe in the insoluble fractions were the lowest, but Cu bioavailability was higher than that of Fe in all fractions. The results provide evidence that the heat-induced insolubilization process adversely affects not only protein but also Cu and Fe bioavailability from legumes and that polyphenols are likely to be a major inhibitor on absorption.     

Glutathione depletion switches nitric oxide neurotrophic effects to cell death in midbrain cultures: implications for Parkinson's disease

Nitric oxide (NO) exerts neurotrophic and neurotoxic effects on dopamine (DA) function in primary midbrain cultures. We investigate herein the role of glutathione (GSH) homeostasis in the neurotrophic effects of NO. Fetal midbrain cultures were pretreated with GSH synthesis inhibitor, l ‐buthionine‐(S,R)‐sulfoximine (BSO), 24 h before the addition of NO donors (diethylamine/nitric oxide‐complexed sodium and S‐nitroso‐N‐acetylpenicillamine) at doses tested previously as neurotrophic. Under these conditions, the neurotrophic effects of NO disappeared and turned on highly toxic. Reduction of GSH levels to 50% of baseline induced cell death in response to neurotrophic doses of NO. Soluble guanylate cyclase (sGC) and cyclic GMP‐dependent protein kinase (PKG) inhibitors protected from cell death for up to 10 h after NO addition; the antioxidant ascorbic acid also protected from cell death but its efficacy decreased when it was added after NO treatment (40% protection 2 h after NO addition). The pattern of cell death was characterized by an increase in chromatin condensed cells with no DNA fragmentation and with breakdown of plasmatic membrane. The inhibition of RNA and protein synthesis and of caspase activity also protected from cell death. This study shows that alterations in GSH levels change the neurotrophic effects of NO in midbrain cultures into neurotoxic. Under these conditions, NO triggers a programmed cell death with markers of both apoptosis and necrosis characterized by an early step of free radicals production followed by a late requirement for signalling on the sGC/cGMP/PKG pathway.     

The involvement of polyphenols and peroxidase activities in heavy-metal accumulation by epidermal glands of the waterlily (Nymphaeaceae)

Co-localization of polyphenols and peroxidase activity was demonstrated in epidermal glands of the waterlily (Nymphaea) by histochemistry. Total phenols, tannins and peroxidase activity were determined quantitatively in plant extracts. Polyphenols were partially identified and were found to consist mainly of hydrolyzable tannins, gallic and tannic acid derivatives.Nymphaea polyphenols were shown to chelate Cr, Hg, and Pb in vitro, and Cd-binding by polymerized polyphenols was demonstrated in leaves exposed to Cd in vivo. Both polyphenols and peroxidases were found at very high constitutive levels, which were not induced or altered by external conditions, such as light and heavy-metal stress. It is suggested that the polymerization of polyphenols by peroxidases, enhanced after heavy-metal uptake and detoxification, is responsible for the binding of heavy metals in Nymphaea epidermal glands. Received: 29 April 2000 / Accepted: 8 June 2000     

Protective Effects of Chlorogenic Acid on Paraquat-induced Oxidative Stress in Rats

The protective effects of chlorogenic acid on paraquat-induced oxidative stress were examined in rats. The activities of erythrocytes and liver glutathione peroxidase, and of both liver catalase and glutathione reductase, which were increased by feeding paraquat, declined to the levels in the control rats by supplementing chlorogenic acid to the paraquat diet. The activity of superoxide dismutase was not changed by dietary paraquat or by supplementing chlorogenic acid to the paraquat diet. Paraquat in the diet markedly decreased the liver triacylglycerol and phospholipid concentrations, as well as the food intake and body weight gain, while chlorogenic acid protected against these decreases. These in vivo results and the in vitro superoxide anion scavenging activity of chlorogenic acid suggest that chlorogenic acid acted preventively against paraquat-induced oxidative stress.     

Molecular docking‐assisted screening reveals tannic acid as a natural protein disulphide isomerase inhibitor with antiplatelet and antithrombotic activities

Protein disulphide isomerase (PDI) promotes platelet activation and constitutes a novel antithrombotic target. In this study, we reported that a PDI‐binding plant polyphenol, tannic acid (TA), inhibits PDI activity, platelet activation and thrombus formation. Molecular docking using plant polyphenols from dietary sources with cardiovascular benefits revealed TA as the most potent binding molecule with PDI active centre. Surface plasmon resonance demonstrated that TA bound PDI with high affinity. Using Di‐eosin‐glutathione disulphide fluorescence assay and PDI assay kit, we showed that TA inhibited PDI activity. In isolated platelets, TA inhibited platelet aggregation stimulated by either GPVI or ITAM pathway agonists. Flow cytometry showed that TA inhibited thrombin‐ or CRP‐stimulated platelet activation, as reflected by reduced granule secretion and integrin activation. TA also reduced platelet spreading on immobilized fibrinogen and platelet adhesion under flow conditions. In a laser‐induced vascular injury mouse model, intraperitoneal injection of TA significantly decreased the size of cremaster arteriole thrombi. No prolongation of mouse jugular vein and tail‐bleeding time was observed after TA administration. Therefore, we identified TA from natural polyphenols as a novel inhibitor of PDI function. TA inhibits platelet activation and thrombus formation, suggesting it as a potential antithrombotic agent.     

Variation in Phenolic Profile, β‐Carotene and Flavonoid Contents,Biological Activities of Two Tagetes Species from Pakistani Flora

The objective of present study was to evaluate the variation in phenolic profile, β‐carotene, flavonoid contents, antioxidant and antimicrobial properties of Tagetes erecta and Tagetes patula (T. erecta and T. patula) through different in vitro assays. Antioxidant activity was determined through 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) free radical scavenging and inhibition of linoleic acid peroxidation assays and antibacterial and antifungal activities studied using the disc diffusion and resazurin microtiter‐plate assays against bacterial and fungal strains. Moreover, total phenolics (TP), total carotenoids (TC) and total flavonoids (TF) were also determined. Highest (TP 35.8 mg GAE/g) and TF (16.9 mg CE/g) contents were found in MeOH extract of T. patula. T. erecta extract showed higher TC contents (6.45 mg/g) than T. patula extract (6.32 mg/g). T. erecta exhibited the highest DPPH radical‐scavenging activity (IC₅₀) (5.73 μg/mL) and inhibition of linoleic acid peroxidation (80.1%). RP‐HPLC revealed the presence of caffeic acid, sinapic acid and ferulic acid in Tagetes extracts, m‐coumaric acid in T. erecta whereas chlorogenic acid in T. patula extract only. Both extracts possessed promising antimicrobial activity compared to the ciprofloxacin and flumequine (+ve controls) against Bacillus subtilis and Alternaria alternate. Both extract were rich source of polyphenols exhibiting excellent biological activities.     

Effects of conjugated linoleic acids on growth performance,serum lysozyme activity,lymphocyte proliferation,and antibody production in broiler chicks

Abstract

This study was conducted to investigate the effect of dietary conjugated linoleic acids (CLA) on growth performance and immune responses in broiler chicks. A total of 240 day-old Arbor Acre male broiler chicks were randomly allotted into four dietary treatments with different inclusion levels of CLA (0, 2.5, 5.0 or 10.0 g/kg) for six weeks. Growth performance, peripheral blood lymphocyte (PBL) proliferation, lysozyme activity, phagocytic activity (carbon clearance) and serum antibody titers against Newcastle disease virus (NDV) vaccine were examined. There were no significant differences in growth performance among treatments (p > 0.05). Chicks fed CLA diets produced more lysozyme activity in serum than the control group at 2 and 6 weeks of age (p < 0.05). Dietary CLA enhanced the PBL proliferation in response to concanavalin A (ConA) at the age of 42 d (p < 0.05). Phagocytic ability was also affected by dietary CLA and chicks fed CLA diets had faster carbon clearance rate (p < 0.05), but antibody titers to NDV was not influenced by dietary CLA. The results of the study suggested that dietary CLA could enhance innate and cellular immune response in broiler chicks, and not affect the growth performance.     

Methionine and Serine Synergistically Suppress Hyperhomocysteinemia Induced by Choline Deficiency,but Not by Guanidinoacetic Acid,in Rats Fed a Low Casein Diet

The effects of dietary supplementation with 0.5% methionine, 2.5% serine, or both on hyperhomocysteinemia induced by deprivation of dietary choline or by dietary addition of 0.5% guanidinoacetic acid (GAA) were investigated in rats fed a 10% casein diet. Hyperhomocysteinemia induced by choline deprivation was not suppressed by methionine alone and was only partially suppressed by serine alone, whereas it was completely suppressed by a combination of methionine and serine, suggesting a synergistic effect of methionine and serine. Fatty liver was also completely prevented by the combination of methionine and serine. Compared with methionine alone, the combination of methionine and serine decreased hepatic S-adenosylhomocysteine and homocysteine concentrations and increased hepatic betaine and serine concentrations and betaine-homocysteine S-methyltransferase activity. GAA-induced hyperhomocysteinemia was partially suppressed by methionine alone, but no interacting effect of methionine and serine was detected. In contrast, GAA-induced fatty liver was completely prevented by the combination of methionine and serine. These results indicate that a combination of methionine and serine is effective in suppressing both hyperhomocysteinemia and fatty liver induced by choline deprivation, and that methionine alone is effective in suppressing GAA-induced hyperhomocysteinemia partially.