Chronic prehepatic portal hypertension in the rat: is it a type of Metabolic Inflammatory Syndrome?

<p>Abstract</p> <p>Background</p> <p>A progressive development of hepatic steatosis with an increase in the lipid hepatocyte content and the formation of megamitochondria have been demonstrated in rats with prehepatic portal hypertension. The aim of this study is to verify the existence of liver and serum lipid metabolism impairments in rats with long-term (2 years) portal hypertension.</p> <p>Methods</p> <p>Male Wistar rats: Control (n = 10) and with prehepatic portal hypertension by triple partial portal vein ligation (n = 9) were used. Liver content of Triglycerides (TG), phospholipids (PL) and cholesterol and serum cholesterol, lipoproteins (HDL and LDL), TG, glucose and Lipid Binding Protein (LBP) were assayed with specific colorimetric commercial kits. Serum levels of insulin and somatostatin were assayed by RIA.</p> <p>Results</p> <p>The liver content of TG (6.30 ± 1.95 <it>vs</it>. 4.17 ± 0.59 μg/ml; p < 0.01) and cholesterol (1.48 ± 0.15 <it>vs</it>. 1.10 ± 0.13 μg/ml; p < 0.001) increased in rats with portal hypertension. The serum levels of cholesterol (97.00+26.02 <it>vs</it>. 114.78 ± 37.72 mg/dl), TG (153.41 ± 80.39 <it>vs</it>. 324.39 ± 134.9 mg/dl; p < 0.01), HDL (20.45 ± 5.14 <it>vs</it>. 55.15 ± 17.47 mg/dl; p < 0.001) and somatostatin (1.32 ± 0.31 <it>vs</it>. 1.59 +0.37 mg/dl) decreased, whereas LDL (37.83 ± 15.39 <it>vs</it>. 16.77 ± 6.81 mg/dl; p < 0.001) and LBP (308.47 ± 194.53 <it>vs</it>. 60.27 ± 42.96 ng/ml; p < 0.001) increased.</p> <p>Conclusion</p> <p>Portal hypertension in the rat presents changes in the lipid and carbohydrate metabolisms similar to those produced in chronic inflammatory conditions and sepsis in humans. These underlying alterations could be involved in the development of hepatic steatosis and, therefore, in those described in the metabolic syndrome in humans.</p

Anti-adhesive activity of cranberry phenolic compounds and their microbial-derived metabolites against uropathogenic Escherichia coli in bladder epithelial cell cultures

This is an open access article distributed under the Creative Commons Attribution License.-- This article belongs to the Special Issue Phenolics and Polyphenolics 2015.Cranberry consumption has shown prophylactic effects against urinary tract infections (UTI), although the mechanisms involved are not completely understood. In this paper, cranberry phenolic compounds and their potential microbial-derived metabolites (such as simple phenols and benzoic, phenylacetic and phenylpropionic acids) were tested for their capacity to inhibit the adherence of uropathogenic Escherichia coli (UPEC) ATCC®53503™ to T24 epithelial bladder cells. Catechol, benzoic acid, vanillic acid, phenylacetic acid and 3,4-dihydroxyphenylacetic acid showed anti-adhesive activity against UPEC in a concentration-dependent manner from 100-500 µM, whereas procyanidin A2, widely reported as an inhibitor of UPEC adherence on uroepithelium, was only statistically significant (p < 0.05) at 500 µM (51.3% inhibition). The results proved for the first time the anti-adhesive activity of some cranberry-derived phenolic metabolites against UPEC in vitro, suggesting that their presence in the urine could reduce bacterial colonization and progression of UTI.This work was funded by the Ministry of Economy and Competitiveness (MINECO) (Projects AGL-2010-17499 and AGL2012-40172-C02-01) and the Comunidad Autónoma de Madrid (Project ALIBIRD S2013/ABI-2728), Spain. Adelaida Esteban-Fernández would like to thank the MINECO-FPI program for her research contract.We acknowledge the support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI).Peer Reviewe

Insights into the metabolism and microbial biotransformation of dietary flavan-3-ols and the bioactivity of their metabolites.

Flavan-3-ols, occurring in monomeric, as well as in oligomeric and polymeric forms (also known as condensed tannins or proanthocyanidins), are among the most abundant and bioactive dietary polyphenols, but their in vivo health effects in humans may be limited because of their recognition as xenobiotics. Bioavailability of flavan-3-ols is largely influenced by their degree of polymerization; while monomers are readily absorbed in the small intestine, oligomers and polymers need to be biotransformed by the colonic microbiota before absorption. Therefore, phenolic metabolites, rather than the original high molecular weight compounds found in foods, may be responsible for the health effects derived from flavan-3-ol consumption. Flavan-3-ol phenolic metabolites differ in structure, amount and excretion site. Phase II or tissular metabolites derived from the small intestine and hepatic metabolism are presented as conjugated derivatives (glucuronic acid or sulfate esters, methyl ether, or their combined forms) of monomeric flavan-3-ols and are preferentially eliminated in the bile, whereas microbial metabolites are rather simple conjugated lactones and phenolic acids that are largely excreted in urine. Although the colon is seen as an important organ for the metabolism of flavan-3-ols, the microbial catabolic pathways of these compounds are still under consideration, partly due to the lack of identification of bacteria with such capacity. Studies performed with synthesized or isolated phase II conjugated metabolites have revealed that they could have an effect beyond their antioxidant properties, by interacting with signalling pathways implicated in important processes involved in the development of diseases, among other bioactivities. However, the biological properties of microbe-derived metabolites in their actual conjugated forms remain largely unknown. Currently, there is an increasing interest in their effects on intestinal infections, inflammatory intestinal diseases and overall gut health. The present review will give an insight into the metabolism and microbial biotransformation of flavan-3-ols, including tentative catabolic pathways and aspects related to the identification of bacteria with the ability to catabolize these kinds of polyphenols. Also, the in vitro bioactivities of phase II and microbial phenolic metabolites will be covered in detail

A survey of modulation of gut microbiota by dietary polyphenols

Dietary polyphenols present in a broad range of plant foods have been related to beneficial health effects. This review aims to update the current information about the modulation of the gut microbiota by dietary phenolic compounds, from a perspective based on the experimental approaches used. After referring to general aspects of gut microbiota and dietary polyphenols, studies related to this topic are presented according to their experimental design: batch culture fermentations, gastrointestinal simulators, animal model studies, and human intervention studies. In general, studies evidence that dietary polyphenols may contribute to the maintenance of intestinal health by preserving the gut microbial balance through the stimulation of the growth of beneficial bacteria (i.e., lactobacilli and bifidobacteria) and the inhibition of pathogenic bacteria, exerting prebiotic-like effects. Combination of in vitro and in vivo models could help to understand the underlying mechanisms in the polyphenols-microbiota-host triangle and elucidate the implications of polyphenols on human health. From a technological point of view, supplementation with richpolyphenolic stuffs (phenolic extracts, phenolic-enriched fractions, etc.) could be an effective option to improve health benefits of functional foods such as the case of dairy fermented foods.The authors of this review were funded by the Spanish MINECO through different projects (AGL2012-40172-C02-01, AGL2010-17499, and BFU2012-35228) and the CONSOLIDER INGENIO 2010 programme (project FUN-CFOOD, CSD2007-063), as well as Comunidad de Madrid (project ALIBIRD P2009/AGR-1469). Montserrat Duenas would like to thank the Spanish “Ramon y Cajal” Programme for a contract.Peer Reviewe

A Survey of Modulation of Gut Microbiota by Dietary Polyphenols

Dietary polyphenols present in a broad range of plant foods have been related to beneficial health effects. This review aims to update the current information about the modulation of the gut microbiota by dietary phenolic compounds, from a perspective based on the experimental approaches used. After referring to general aspects of gut microbiota and dietary polyphenols, studies related to this topic are presented according to their experimental design: batch culture fermentations, gastrointestinal simulators, animal model studies, and human intervention studies. In general, studies evidence that dietary polyphenols may contribute to the maintenance of intestinal health by preserving the gut microbial balance through the stimulation of the growth of beneficial bacteria (i.e., lactobacilli and bifidobacteria) and the inhibition of pathogenic bacteria, exerting prebiotic-like effects. Combination of in vitro and in vivo models could help to understand the underlying mechanisms in the polyphenols-microbiota-host triangle and elucidate the implications of polyphenols on human health. From a technological point of view, supplementation with rich-polyphenolic stuffs (phenolic extracts, phenolic-enriched fractions, etc.) could be an effective option to improve health benefits of functional foods such as the case of dairy fermented foods

Phenolic assesment of Uncaria tomentosa L. (cat’s claw): Leaves, stem, bark and wood extracts

This article belongs to the Special Issue "Recent Advances in Plant Phenolics".-- This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license.The phenolic composition of extracts from Uncaria tomentosa L. from different regions of Costa Rica was studied using advanced analytical techniques such as UPLC/TQ-ESI-MS and 13C-NMR. Samples from leaves, stems, bark and wood (n = 22) were subjected to extraction to obtain phenolic and alkaloid extracts, separately. Comparatively, higher values of total phenolic content were observed for leaves, stems and bark (225–494 gallic acid equivalents/g) than for wood extracts (40–167 gallic acid equivalents/g). A total of 32 non-flavonoid and flavonoid compounds were identified in the phenolic extracts: hydroxybenzoic acids (benzoic, salicylic, 4-hydroxybenzoic, prochatechuic, gallic, syringic and vanillic acids), hydroxycinnamic acids (p-coumaric, caffeic, ferulic and isoferulic acids), flavan-3-ols monomers [(+)-catechin and (−)-epicatechin)], procyanidin dimers (B1, B2, B3, B4, B5, B7 and two other of unknown structure) and trimers (C1, T2 and one of unknown structure), flavalignans (four unknown structures pertaining to the cinchonain family) and propelargonidin dimers (four unknown structures, reported for the first time in U. tomentosa). Additionally, alkaloid extracts obtained from the plant residue after phenolic extraction exhibited a content of tetracyclic and pentacyclic alkaloids ranging between 95 and 275 mg/100 g of dry material for bark extracts, and between 30 and 704 mg/100 g for leaves extracts. In addition, a minor alkaloid was isolated and characterized, namely 18,19-dehydrocorynoxinoic acid. Our results confirmed the feasibility of U. tomentosa as a suitable raw material for obtaining phenolic- and alkaloid-rich extracts of potential interest.This project was partially funded by a grant from the Spanish International Development Cooperation Agency (AECID) (Refs. A/023397/09 and A/030037/10) and a joint grant from the Costa Rica-USA Foundation (CRUSA) and the Spanish Scientific Research Council (CSIC) (Ref. CR0024).We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI).Peer reviewe

Cranberry-derived phenolic metabolites and urinary tract infections

Resumen del póster presentado a la 7th International Conference on Polyphenols and Health, celebrada en Tours (Francia) del 27 al 30 de octubre de 2015.The beneficial effects of cranbeny products against urinary tract infections (UTIs) have been attributed, at least partly, to their A-type proanthocyanidin (PAC) content. A-type PACs have shown uropathogenic Escherichia coli (UPEC)-anti-adhesive activity, although they are unlikely to appear in urine at relevant concentrations as they are poorly absorbed. One leading hypothesis is that PAC-derived metabolites present in urine would operate in the phase of UPEC adyherence to uroepithelial cells, preventing bacterial colonization. In addition to this, and as it is becoming evident that the intestine is a reservoir for uropathogenic bacteria, other hypothesis is that. A-type proanthocyanidins specifically decrease the transient intestinal colonisation b UPEC, consequently reducing the risk of UTI incidence. In any case, gut microbiota (and its inter-individual variability) seems to be an important factor to be considered. In this communication, we summarize our results from different approaches aimed to look into the mechanisms that are behind the protedive action of cranberry polyphenols against ITUs: 1)in vitro fermentations of cranbeny polyphenols with colonic microbiota, that were performed to access the microbial-derived metabolic profile of cranbeny polyphenols as well as their effect on gut microbiota survival, 2) an in vivo trial with model mouse intraurethral-inoculated wilh UPEC, that evaluated the effectiveness of cranbeny supplementation in bacterial infection as well as its impact on faecal phenolic metabolism and faecal microbiota, 3) testing the UPEC-antiadhesive capacity of cranbeny phenolic compounds and their metabolites in bladder epithelial cell culíures, and 4) ex vivo studies of UPEC-antiadhesive capacity of mice mines collected after cranbeny supplementation.Ministry of Economy and Competitiveness (MiNECO) (Projects AGL-2010-17499 and AGL2012-40172-C02-01) and the Comunidad Autónoma de Madrid (Project ALIBIRD S2013/ABI-2728), Spain.Peer Reviewe

Comparative effects of A- and B-type proanthocyanidins in the prevention of urinary tract infection in mice

Resumen del póster presentado a la VI International Conference on Polyphenols and Health celebrada en Buenos Aires (Argentina) del 16 al 19 de octubre de 2013.Consumption of cranberry (Vaccinium macrocarpum) is widely recommended forprophylaxis against urinary tract infections (UTI) in women. Among cranberry components, A-type proanthocyanins would be implicated in these preventive effects against UTI. However, proanthocyanidins are poorly absorbed in the small intestine, but subjected to extensive biotransformation in the colon, although studies are almost restricted to B-type proanthocyanidins. Therefore, the hypothesis of this study is that urinary metabolome from of A-type and B-type proanthocyanidins-mainly derived from their colonic catabolism-differ,and only metabolites from the A-type procyanidins have protective effects against UTI. To test this hypothesis, JAXc3H/OuJ female mice previously fed with specific diet (control, 1% cranberry extract and 1% grape seed extract) for 2 weeks, were inoculated with the uropathogenic E. coli (ATCC 53503™) to provoke infection, and maintained 2 weeks more before being sacrificed. Urine samples were collected at different times and subjected to E.coli counting, leukocytary esterase and nitrites analyses, and mieloperoxidase task. Samples of kidney and bladder tissues were also collected for E. coli counting and histopathologic analysis. Additionally, the capacity of the urine samples to inhibit bacterial adherence was tested in the T24 bladder cell line (ATCC HTB4 ™).Peer reviewe