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Immunohistochemical localization of nNOS and VIP in the mantle integument of the mussel, Mytilus galloprovincialis.

The phylogeny and functional roles of many bioactive compounds in the invertebrate integument are still unclear. In order to deal with this issue, we performed an immunohistochemical investigation of the integument of the mussel, Mytilus galloprovincialis, to demonstrate the presence of nNOS- and VIP-positive nerve fibers in subepidermal connective tissue of the mantle. Positive nerve cell bodies were detected in this tissue as well as in cortex of sperm follicles, and adjacent to maturating oocytes and spermatocytes located in the thickness of the mantle. These results indicate involvement of a local inhibitory non-adrenergic-non-cholinergic (NANC) regulatory mechanism of epidermal functions, such as mucous secretion and ciliary beating. At the gonadic level, this mechanism probably regulates the cycle of maturation and release of the gametes in both sexes.

Adrenergic Fibers↗

Modulatory effect of Piperine on mitochondrial antioxidant system in Benzo(a)pyrene-induced experimental lung carcinogenesis.

Chemoprevention has emerged as a very effective preventive measure against carcinogenesis. Many bioactive compounds present in edible as well in herbal plants have revealed their cancer chemopreventive potential. In the present study, our goal was to investigate the impact of piperine, a principle ingredient of pepper, on alterations of mitochondrial antioxidant system and lipid peroxidation in Benzo(a)pyrene (B(a)P) induced experimental lung carcinogenesis. Oral supplementation of piperine (50 mg/kg body weight) effectively suppressed lung carcinogenesis in B(a)p induced mice as revealed by the decrease in the extent of mitochondrial lipid peroxidation and concomitant increase in the activities of enzymatic antioxidants (superoxide dismutase, catalase and glutathione peroxidase) and non enzymatic antioxidant (reduced glutathione, vitamin E and vitamin C) levels when compared to lung carcinogenesis bearing animals. Our data suggests that piperine may extent its chemopreventive effect by modulating lipid peroxidation and augmenting antioxidant defense system.

Alkaloids↗

Bioactivity of secoiridoid glycosides from Centaurium erythraea.

As part of our on-going search for bioactive compounds from Scottish plants, two secoiridoid glycosides, swertiamarin and sweroside, have been isolated from the aerial parts of Centaurium erythraea Rafn (Family: Gentianaceae) by reversed-phase preparative HPLC coupled with a photo-diode-array detector. The structures of these compounds were elucidated unambiguously by UV, FABMS and extensive 1D and 2D NMR spectroscopic analyses and also by comparing experimental data with literature data. Antibacterial, free radical scavenging activities and general toxicity of these glycosides have been assessed. Both compounds inhibited the growth of Bacillus cereus, Bacillus subtilis, Citrobacter freundii and Escherichia coli. While swertiamarin was also active against Proteus mirabilis and Serratia marcescens, sweroside inhibited the growth of Staphylococcus epidermidis. Swertiamarin and sweroside exhibited significant general toxicity in brine shrimp lethality bioassay and the LD50 values were 8.0 microg/ml and 34 microg/ml, respectively, whereas that of the positive control podophyllotoxin, a well known cytotoxic lignan, was 2.79 microg/ml. Chemotaxonomic implications of these compounds in the family Gentianaceae have also been discussed briefly.

Animals↗

Functional foods: Latin American perspectives.

The perspectives of Latin America as a potential producer and consumer of functional foods will depend largely on the level of information and income of the population, credibility of the products, research investments and regulatory practices. The characteristics of Latin America are diverse at the regional and sub-regional levels. However, as part of the demographic and epidemiological transition currently underway, common trends can be identified such as increasing urbanization and life expectancy, the occurrence of obesity and malnutrition, increasing incidences of chronic diseases and causes of mortality rates, all of which suggests the importance of diet and functional foods in public health policies. The Latin American population in general has no knowledge of functional foods, but in the more urbanized areas there is an increasingly health-conscious consumer, aware of the importance of food for health, due to the media and local traditions. More investment in research is important to explore the existing plant biodiversity that is a rich source of new foods and bioactive compounds, some of which are already used for health improvement and well-being. Clinical validation of functional foods should consider functional food science concepts and also the diverse cultural and genetic background of the local population. In Latin American scientific and regulatory communities, the functional foods concept has been associated with foods having health benefits beyond those of basic nutrition but is not defined officially in the emerging regulatory codes. Regulation existing in some countries is focused on safety and efficacy; both functional and health claims are allowed (risk reduction) provided they have scientific validation. This allowed introduction on the market of several products with health claims, some of them submitted to post-marketing surveillance.

Dietary Supplements↗

Antioxidant capacity of vegetables, spices and dressings relevant to nutrition.

Vegetables are the most important sources of phenolics in the Mediterranean diet. Phenolics, especially flavonoids, are suggested as being essential bioactive compounds providing health benefits. In this study, twenty-seven vegetables, fifteen aromatic herbs and some spices consumed in Central Italy (the Marches region) were studied to reveal total phenolic, flavonoid and flavanol content as well as their antioxidant capacity measured by the oxygen radical absorbance capacity (ORAC) method. A comparison in terms of antioxidant capacity was made between different salads, as well as between salads to which aromatic herbs had been added. Lemon balm and marjoram at a concentration of 1.5 % w/w increased by 150 % and 200 % respectively the antioxidant capacity of a salad portion. A 200 g portion of a salad enriched with marjoram corresponded to an intake of 200 (SD 10) mg phenolics and 4000 (SD 300) ORAC units (micromol Trolox equivalents). Olive oils and wine or apple vinegars were the salad dressings that provided the highest increase in antioxidant capacity. Among the spices tested, cumin and fresh ginger made the most significant contribution to the antioxidant capacity. The results are useful in surveying the antioxidant parameters of vegetables, herbs and spices produced and consumed in our geographical area as well as in quantifying the daily intake of phenolics and ORAC units. The results can be used in public health campaigns to stimulate the consumption of vegetables able to provide significant health protection in order to prevent chronic diseases.

Antioxidants↗

The case for strategic international alliances to harness nutritional genomics for public and personal health.

Nutrigenomics is the study of how constituents of the diet interact with genes, and their products, to alter phenotype and, conversely, how genes and their products metabolise these constituents into nutrients, antinutrients, and bioactive compounds. Results from molecular and genetic epidemiological studies indicate that dietary unbalance can alter gene-nutrient interactions in ways that increase the risk of developing chronic disease. The interplay of human genetic variation and environmental factors will make identifying causative genes and nutrients a formidable, but not intractable, challenge. We provide specific recommendations for how to best meet this challenge and discuss the need for new methodologies and the use of comprehensive analyses of nutrient-genotype interactions involving large and diverse populations. The objective of the present paper is to stimulate discourse and collaboration among nutrigenomic researchers and stakeholders, a process that will lead to an increase in global health and wellness by reducing health disparities in developed and developing countries.

Animals↗

Rye, lignans and human health.

Rye bran contains a high content not only of dietary fibre, but also of plant lignans and other bioactive compounds in the so-called dietary fibre complex. Blood concentrations of lignans such as enterolactone have been used as biomarkers of intake of lignan-rich plant food. At present,evidence from studies in human subjects does not warrant the conclusion that rye, whole grains orphyto-oestrogens protect against cancer. Some studies, however, have pointed in that direction,especially in relation to cancers of the upper digestive tract. A number of prospective epidemiological studies have clearly shown a protective effect of wholegrain cereals against myocardial infarctions. A corresponding protective effect against diabetes and ischaemic stroke(brain infarct) has also been demonstrated. It seems reasonable to assume that these protective effects are associated with one or more factors in the dietary fibre complex.

Cardiovascular Diseases↗

Carrot Juice Intake Modulates Oncogenic and Inflammatory Pathways in Advanced Colorectal Adenomas: A Pilot Feasibility Study.

Carrots are a rich dietary source of carotenoids and polyacetylenes, bioactive compounds with demonstrated anti-inflammatory and anticancer properties in experimental models. Epidemiological evidence suggests that carrot consumption is associated with a reduced risk of colorectal cancer; however, clinical data linking carrot intake to molecular changes in premalignant colorectal tissue remain limited. In this pilot intervention study, 20 patients with advanced colorectal adenomas were enrolled. Fifteen participants consumed carrot juice daily for 21 days, while five served as untreated controls. Paired adenoma biopsies were collected before and after the intervention and were analyzed using gene expression microarrays to assess transcriptional responses. Carrot juice intake was well tolerated, with adherence exceeding 95% and no reported adverse events. Transcriptomic analysis revealed modulation of key pathways implicated in colorectal carcinogenesis, including downregulation of the WNT, PI3K-AKT, and MAPK signaling pathways, as well as cyclooxygenase-2-related inflammatory pathways and cytokine signaling. These changes were consistent with reduced oncogenic signaling and attenuation of inflammatory activity within adenoma tissue. In summary, short-term carrot juice consumption was associated with coordinated suppression of molecular pathways involved in colorectal adenoma progression. These findings provide preliminary clinical evidence that a whole-food dietary intervention may influence early carcinogenic processes and support the need for larger controlled studies evaluating clinical outcomes.

Journal Article↗

Inhibition of skin carcinomas but not papillomas by sphingosine, N-methylsphingosine, and N-acetylsphingosine.

The sphingoid base backbones of sphingolipids are highly bioactive compounds that affect cell growth, differentiation, diverse cell behaviors, and programmed cell death. Therefore, the efficacy of sphingosine (SPH) and the analogs N-acetylsphingosine (NAS), N-methylsphingosine (NMS), octylamine (OCT), and sterylamine (STR) in the prevention of skin cancer was assessed in female Sencar mice by measuring effects on the induction of epidermal ornithine decarboxylase (ODC) activity and hyperplasia by 12-O-tetradecanoylphorbol-13-acetate (TPA) and effects on the induction of skin tumors by 7, 12-dimethylbenz[a]anthracene (DMBA) and TPA. ODC was measured in the shaved dorsal skin of mice treated topically with 0.05-20 mumol of these compounds 30 minutes before application of 8.5 nmol of TPA in 0.2 ml of acetone. ODC activity was inhibited by > or = 5 mumol of SPH and STR, > or = 10 mumol of NAS and NMS, and 20 mumol of OCT. In contrast, the induction of hyperplasia was not inhibited by application of these compounds 30 minutes before TPA. Two carcinogenesis studies were conducted with 10 nmol of DMBA as the initiator and 3.2 nmol of TPA (2x/wk for 15 wk) as the promoter. In the first study, NAS, NMS, OCT, and STR (0.05 and 0.5 mumol) were applied before each TPA application. Papilloma incidence and multiplicity were not inhibited, but NAS (0.05 mumol) and NMS (0.05 and 0.50 mumol) increased cancer-free survival. In the second experiment, SPH, NAS, and NMS (0.05 and 0.5 mumol) were applied 30 minutes before each TPA treatment and twice weekly for 10 weeks after the final TPA treatment. Papilloma incidence and multiplicity were not inhibited; however, the proportion of mice without carcinoma was increased by both doses of SPH and by 0.5 mumol of NAS. Thus low doses of sphingolipids that were not effective in inhibiting ODC activity, reducing hyperplasia, or preventing epidermal papilloma development were, nonetheless, effective in inhibiting carcinoma development.

Amines↗

Perspectives of the chemical fate and toxicity of pesticides.

The wide-spread use of pesticides in modern agriculture has created a need to investigate the chemical transformation of pesticides in plants and animals. This paper reviews the chemical and biochemical fate of various pesticides and other xenobiotics. Photochemical mechanisms appear to be the most common pathways for the abiotic transformation of these chemicals. Biotic transformation includes a large group of biochemical reactions which may result in either deactivation (detoxication) or activation (toxication) of bioactive compounds. The need for quality control in the production of pesticides is also discussed.

Animals↗

Soy isoflavones--benefits and risks from nature's selective estrogen receptor modulators (SERMs).

Phytoestrogens have become one of the more topical areas of interest in clinical nutrition. These non-nutrient bioactive compounds are ubiquitous to the plant kingdom and possess a wide range of biological properties that contribute to the many different health-related benefits reported for soy foods and flaxseeds--two of the most abundant dietary sources of phytoestrogens. Reviewed is the recent knowledge related to their pharmacokinetics and clinical effects, focusing mainly on isoflavones that are found in high concentrations in soy foods. Arguments are made for considering soy isoflavones as natural selective estrogen receptor modulators (SERMs) based upon recent data of their conformational binding to estrogen receptors. Rebuttal is made to several key and important issues related to the recent concerns about the safety of soy and its constituent isoflavones. This article is not intended to be a comprehensive review of the literature but merely highlight recent research with key historical perspectives.

Biological Availability↗

Regulation of adiposity and obesity risk by dietary calcium: mechanisms and implications.

Dietary calcium plays a pivotal role in the regulation of energy metabolism; high calcium diets attenuate adipocyte lipid accretion and weight gain during periods of overconsumption of an energy-dense diet and increase lipolysis and preserve thermogenesis during caloric restriction, thereby markedly accelerating weight loss. Intracellular Ca2+ has a key role in regulating adipocyte lipid metabolism and triglyceride storage, with increased intracellular Ca2+ resulting in stimulation of lipogenic gene expression and lipogenesis, suppression of lipolysis, and increased lipid filling and adiposity. Moreover, we have recently demonstrated that the increased calcitriol released in response to low calcium diets stimulates Ca2+ influx in human adipocytes and thereby promotes adiposity. Accordingly, suppressing calcitriol levels by increasing dietary calcium is an attractive target for the prevention and management of obesity. In support of this concept, transgenic mice expressing the agouti gene specifically in adipocytes (a human-like pattern) respond to low calcium diets with accelerated weight gain and fat accretion, while high calcium diets markedly inhibit lipogenesis, accelerate lipolysis, increase thermogenesis and suppress fat accretion and weight gain in animals maintained at identical caloric intakes. Further, low calcium diets impede body fat loss, while high calcium diets markedly accelerate fat loss in transgenic mice subjected to caloric restriction. These findings are further supported by clinical and epidemiological data demonstrating a profound reduction in the odds of being obese associated with increasing dietary calcium intake. Notably, dairy sources of calcium exert a significantly greater anti-obesity effect than supplemental sources in each of these studies, possibly due to the effects of other bioactive compounds, such as the angiotensin converting enzyme inhibitor found in milk, on adipocyte metabolism, indicating an important role for dairy products in the control of obesity.

Adipocytes↗

Molecular dynamics simulation of anesthetic-phospholipid bilayer interactions.

To probe the hypothesis of a lipid-mediated mechanism of general anesthetic action on a molecular level, and to help elucidate the nature of the interactions of bioactive compounds with membranes, the effects of trichloroethylene (TCE), an inhalational general anesthetic, on a dioleoylphosphatidylcholine (DOPC) lipid bilayer have been investigated by molecular dynamics (MD) simulations at 37 degrees C and 1 atm and the results compared with 31P and 2H NMR experimental studies (Ref 1). The model used included a single TCE molecule embedded in a lipid bilayer consisting of 24 DOPC molecules and an 8 A layer of explicit water of solvation in each polar head group region of the bilayer, together with constant-pressure periodic boundary conditions in three dimensions. A comparison of the bilayer properties calculated in the presence and absence of the anesthetic led to the detection of three major perturbations of the bilayer caused by the anesthetic at 1 atm: i) an increase in the ratio of the effective areas of hydrocarbon tails and the head group per lipid, predicting the tendency of lipids near the anesthetic site of action to form a hexagonal phase (HII); ii) a slight increase in the frequency of chain dihedral angles found in the gauche conformation; and iii) a significant increase in the lateral mean-square displacement of lipid molecules, an indication of increased lipid lateral diffusion and membrane fluidity. The pressure antagonism of these effects was also studied by MD simulations at pressures of 200 and 400 atm. The study of the pressure reversibility of these effects at 200 and 400 atm indicated that they were partially prevented at 200 atm and essentially blocked at 400 atm, suggesting their probable relevance to the pressure reversal effect seen with general anesthesia. These results may thus provide insights into the interaction between general anesthetics and similar small organic molecules with membranes.

Computer Graphics↗

A novel total synthesis of kinsenoside and goodyeroside A relying on the efficient reaction of the chiral 2(5H)-furanones.

A new total synthesis of the bioactive compounds, kinsenoside and goodyeroside A, has been accomplished from readily available starting materials. The chiral 2(5H)-furanone and its enantiomer were employed as the key chiral intermediates to construct the chiral glycosides and with the appropriate stereochemistry. The spectral data of the target compounds and their acetylated derivatives and are identical with those of the natural and corresponding acetylated products.

4-Butyrolactone↗

Antitumor components from an actinomycete strain 6011W.

Three bioactive compounds that inhibited nucleoside transport were isolated from the cultured broth of Streptoverticillium sp. 6011W. The structures of those compounds were characterized as cinnamamide, N-(tetrahydro-2-oxo-3-thienyl)-acetamide and benzamide, respectively. They all inhibited radiolabeled thymidine transport into Ehrlich carcinoma cells, with IC50 values of 30.4, 97.2 and 85.4 microM, respectively. When administered i.p., cinnamamide not only inhibited the growth of transplanted tumors but also reduced the number of lung metastases in mice bearing Lewis lung carcinoma. The results suggest that nucleoside transport inhibition assay is a valuable model to search for antitumor agents of natural origin.

Actinomycetales↗

Potential impact of strawberries on human health: a review of the science.

Epidemiological studies have noted a consistent association between the consumption of diets rich in fruits and vegetables and a lower risk for chronic diseases including cancer and cardiovascular disease. There is accumulating evidence that much of the health-promoting potential of these plant foods may come from phytochemicals, bioactive compounds not designated as traditional nutrients. In strawberries, the most abundant of these are ellagic acid, and certain flavonoids: anthocyanin, catechin, quercetin and kaempferol. These compounds in strawberries have potent antioxidant power. Antioxidants help lower risk of cardiovascular events by inhibition of LDL-cholesterol oxidation, promotion of plaque stability, improved vascular endothelial function, and decreased tendency for thrombosis. Furthermore, strawberry extracts have been shown to inhibit COX enzymes in vitro, which would modulate the inflammatory process. Individual compounds in strawberries have demonstrated anticancer activity in several different experimental systems, blocking initiation of carcinogenesis, and suppressing progression and proliferation of tumors. Preliminary animal studies have indicated that diets rich in strawberries may also have the potential to provide benefits to the aging brain.

Antioxidants↗

Microemulsions: a potential delivery system for bioactives in food.

Microemulsions are thermodynamically stable, transparent, low viscosity, and isotropic dispersions consisting of oil and water stabilized by an interfacial film of surfactant molecules, typically in conjunction with a cosurfactant. Microemulsions (so-called due to their small particle size; 5-100 nm) have found application in a wide variety of systems, such as pharmaceutical and oil recovery, but their application in food systems has been hindered by the types of surfactant permissible for use in food. The objective of this review is to provide an overview of the structures and phase behavior of microemulsions, methods of microemulsion formation, and techniques which may be used for characterization. A comprehensive review of previous work on both food-grade microemulsion systems, and non-food-grade systems of specific food interest is included. The application of microemulsions as reaction media, their ability to solubilize proteins and hence their use as a separation technique is also documented. In addition, attention is focused on the application of microemulsions as delivery systems for delivery of bioactive compounds, and the links between microemulsions and increased bioavailability. Future research, both applied and fundamental, should focus on surfactants which are not restricted for use in foods.

Chemical Phenomena↗

A physico-chemical approach of polyanion-polycation interactions aimed at better understanding the in vivo behaviour of polyelectrolyte-based drug delivery and gene transfection.

Polyanions and polycations are known to interact electrostatically and form soluble or insoluble polyelectrolyte complexes. Body fluids, blood and cells are composed of many polyelectrolytic systems such as proteins, glycoproteins, poly(glycosamino glycane)s, polynucleotides, etc. under physiological conditions. Nowadays synthetic polyelectrolytes are proposed as carriers of bioactive compounds, such as drugs and genes, and are thus to be injected into body fluids. For the sake of better understanding the complex behaviour of such artificial polyelectrolytic systems in the pool of natural polyelectrolytes forming living systems, interactions of bi- and multi-components mixtures of synthetic polyanions with the same synthetic polycation, namely poly[(dimethylaminoethyl) methacrylate], HCl, were investigated under the conditions imposed by physiological media, namely pH = 7.4, ionic strength mu = 0.15 and T = 37 degrees C. The selected artificial polyanions were the sodium salts of poly(acrylic acid), poly(methacrylic acid), poly(L-lysine citramide) and poly(styrene sulfonic acid) which have different acid strength, charge density and ionogenic group. The influence of ionic strength and pH on complex formation and stability was investigated by turbidimetry at lambda = 520 nm. Phase separation occurred regardless of ionic strength in the case of sodium polystyrene sulfonate. For the other polyanions, redissolution was observed at critical NaCl concentrations much higher than the physiological ionic strength. In the case of mixtures of two or three polyanions with the polycation, the complex formation appeared polyanion-selective at physiological ionic strength. Data are discussed with regard to phenomena that can occur in vivo.

Acrylic Resins↗