1,721,017 research outputs found

    Anthocyanins in Colorectal Cancer Prevention. A Systematic Review of the Literature in Search of Molecular Oncotargets

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    Background: Colorectal cancer (CRC) is the malignant process that surges in the terminal part of gastrointestinal tract when adenomatous polyps convert to neoplastic cells able to infiltrate the submucosa. Despite the constant progress in applying preventive measures (screening, colonoscopy) and developing new cures (surgical and chemotherapy), CRC is still one of the leading causes of cancer death worldwide. The importance of natural dietary components in CRC prevention has been recognized. Defining the precise role of the diet and its particular molecular moieties in CRC prevention is of constant scientific interest years behind. Anthocyanins (AC), phenolic phytochemicals present in pigmented plants and vegetables, have been reported to have some role in counteracting CRC carcinogenesis. Nonetheless, evidence coming out the pre-clinical, clinical, and epidemiological studies is still controversial. This review is addressing the need to better comprehend the causes of missing data and discrepancies in investigations on the role of dietary AC in modulating CRC carcinogenesis. Methods: We have analyzed the scientific literature, available in PubMed database, according to PRISMA (Preferred Reporting Items for Systematic Reviews and MetaAnalyses) statement methodology for systematic reviews. Subsequently, two selection strategies, with their screening and eligibility criteria, were applied to retain research articles reporting in vitro and in vivo studies aimed at exploring the molecular mechanisms underlying the observed effects of AC in CRC prevention. Results: From the pool of 82 identified publications, we selected 19 articles reporting experimental or observational data on the effect of AC-enriched diets in CRC prevention in humans or murine species. Furthermore, we selected 10 articles reporting about molecular mechanisms of action of pure AC in CRC experimental models. Conclusions: The major outcome of this review is that AC showed essentially no effect in human studies, whereas AC-enriched diets proved to be effective in experimental murine models of CRC. In cell culture tests, AC showed to interfere with cell signaling pathways related to cell growth and differentiation, apoptosis, oxygen stress, and inflammation response. Further molecular characterizations are required to include AC in the panel of disease-modifying agents

    Bioavailability of flavonoids: in vitro methods for assessing bilitranslocase-mediated membrane transport

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    B ilitranslocase (TC 2.A.65.1.1) is a plasma membrane transporter expressed in the gastro-intestinal epithelium (luminal side), the liver and kidney (vascular side) (1) and in the vascular endothelium (2). It transports bilirubin, flavonoids and other organic anions. By using specific anti-sequence bilitranslocase antibodies targeting extracellular epitopes critical for the carrier function, we can investigate both the tissue and cellular localisation of the protein and its function in absorption and tissue distribution of flavonoids, by a system of in vitro methods featured by increasing structural complexity: i) plasma membrane vesicles, ii) cell cultures, iii) tissue fragments, and iv) isolated organs. The best example of implementation of this chain of in vitro methods is the cardiovascular system, where consistent observations were obtained throughout the chain. It can be concluded that the first method, i.e. a bilitranslocase-specific functional assay (3) in membrane vesicles where potential ligands (competitive and non-competitive inhibitors) are identified, yields data predictive of bilitranslocase function in organs. This approach can be helpful for exploiting bilitranslocase as a membrane transporter in drug targeting and development. 1 Passamonti S, Terdoslavich M, Franca R, Vanzo A, Tramer F, Braidot E, et al. Curr Drug Metab. 2009 May;10(4):369-94. 2 Maestro A, Terdoslavich M, Vanzo A, Kuku A, Tramer F, Nicolin V, et al.. Cardiovasc Res. 2009 Aug 25. 3 Passamonti S, Tramer F, Petrussa E, Braidot E, Vianello A. In: FettNeto AG, editor. Plant Secondary Metabolism Engineering Methods and Applications. Totowa, NJ: Humana Press Inc.; 2010

    Exceptionally fast uptake and metabolism of cyanidin 3-glucoside by rat kidneys and liver.

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    To asses the hypothesis that anthocyanins are rapidly taken up from the blood into tissues, where they accumulate up to their bioactivity threshold, an intravenous dose of cyanidin 3-glucoside (1) was administered to anaesthetized rats. Cyanidin 3-glucoside (1) and its metabolites were analyzed in the plasma, kidneys, liver, urine, and bile, using last-generation mass spectrometry. Compound 1 was found to rapidly disappear from plasma (t/2=0.36 min). As soon as 15 s after its administration, both 1 and its methylation product, peonidin 3-glucoside (2), were detected in the plasma, kidneys, and liver. At 1 min, both 1 and 2 had almost disappeared from the plasma, but attained their peak concentrations in the kidneys and in the liver. Compound 2 was rapidly excreted both in the bile and in the urine. Three additional methylated metabolites were detected in traces, namely, delphinidin 3-glucoside (3), petunidin 3-glucoside (4), and malvidin 3-glucoside (5). These data contribute to solving the paradox of the high bioactivity of anthocyanins in spite of their apparent low bioavailability

    Dietary anthocyanins: are they micronutrients?

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    Dietary anthocyanins might be seen as micronutrients. Even though they are abundant in fruits and vegetables, and thus also in our diet, they occur in plasma and tissues only in trace amounts. However, they profoundly af ect cellular metabolism, organ functioning, and have strong clinical-epidemiological evidence supporting their health-promoting ef ects

    The endothelial plasma membrane transporter bilitranslocase mediates rat aortic vasodilation induced by anthocyanins.

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    BACKGROUND AND AIMS: Anthocyanins, a sub-class of flavonoids, induce endothelium-dependent vasorelaxation, by activating endothelial nitric oxide synthase and consequently increasing production of the vasorelaxant agent nitric oxide. It is not yet clear if anthocyanin-induced vasorelaxation starts with their interaction with plasma membrane receptors in the extracellular compartment, or with their membrane transport toward intracellular molecular targets. We therefore investigated the possible role of bilitranslocase (TC 2.A.65.1.1), an endothelial plasma membrane carrier that transports flavonoids, in the vasodilation activity induced by anthocyanins. METHODS AND RESULTS: Vascular reactivity was assessed in thoracic aortic rings obtained from male Wistar rats. Pre-treatment of aortic rings with anti-sequence bilitranslocase antibodies targeting the carrier, decreased vasodilation induced by cyanidin 3-glucoside and bilberry anthocyanins. CONCLUSION: Here we show for the first time that bilitranslocase mediates a critical step in vasodilation induced by anthocyanins. This offers new insights into the molecular mechanism involved in endothelium-dependent vasorelaxation by flavonoids, and the importance of their specific membrane carriers

    Fluorometric Nanoscale Analysis of Bilirubin and Biliverdin in Human Cerebrospinal Fluid

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    Cerebrospinal fluid (CSF) is a valuable source for the quantification of soluble, brain-specific biomarkers supporting the diagnosis of some neurological disorders, infectious diseases, and suspected subarachnoid hemorrhage. Given the increasing need to expand the basic knowledge of brain pathophysiology for disease biomarker discovery, we set the goal to quantify bilirubin and biliverdin in human CSF. Their concentrations are expected to reflect the level of brain heme catabolism, a key pathway involved in the biological response to oxidative stress. Here, we present the results of the CSF analysis by a specific and sensitive fluorometric method using the recombinant fusion protein HELP-UnaG (HUG). The concentrations of bilirubin and biliverdin in 50 human CSF samples were in the ranges of 14-340 and 0-66 nM, respectively. This assay can be easily implemented in small-scale laboratories and neurological units for the routine analysis of clinical CSF samples
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