Modulation of (-)-Epicatechin Metabolism by Coadministration with Other Polyphenols in Caco-2 Cell Model

ABSTRACT Widely consumed beverages such as red wine, tea, and cocoaderived products are a great source of flavanols. Epidemiologic and interventional studies suggest that cocoa flavanols such as (-)-epicatechin may reduce the risk of cardiovascular diseases. The interaction of (-)-epicatechin with food components including other polyphenols could modify its absorption, metabolism, and finally its bioactivity. In the present study we investigate (-)-epicatechin absorption and metabolism when coexposed with other polyphenols in the intestinal absorptive Caco-2 cell model. Depending on the type of polyphenols coadministered, the total amount of 39-O-methyl-epicatechin and 39-O-sulfate-epicatechin conjugates found both in apical and basal compartments ranged from 19 to 801 nM and from 6 to 432 nM, respectively. The coincubation of (-)-epicatechin with flavanols, chlorogenic acid, and umbelliferone resulted in similar amounts of 39-O-methyl-epicatechin effluxed into the apical compartment relative to control. Coincubation with isorhamnetin, kaempferol, diosmetin, nevadensin, chrysin, equol, genistein, and hesperitin promoted the transport of 39-Omethyl-epicatechin toward the basolateral side and decreased the apical efflux. Quercetin and luteolin considerably inhibited the appearance of this (-)-epicatechin conjugate both in the apical and basolateral compartments. In conclusion, we could demonstrate that the efflux of (-)-epicatechin conjugates to the apical or basal compartments of Caco-2 cells is modulated by certain classes of polyphenols and their amount. Ingesting (-)-epicatechin with specific polyphenols could be a strategy to increase the bioavailability of (-)-epicatechin and to modulate its metabolic profile

Synthèse totale énantiosélective de l'acide barbacénique

Ce travail de thèse décrit la première synthèse totale énantiosélec tive de l'acide barbacénique, un bisnorditerpène isolé de la plante Barbacenia flava. Ce composé tricyclique polyfonctionnalisé, constitué d'un squelette carboné inédit, possède cinq centres stéréogènes contigus dont quatre quaternaires. Les deux stratégies synthétiques présentées reposent sur une étape d'addition conjuguée sur deux énones différentes permettant de construire le centre quaternaire le plus encombré. Pour cela, elles utilisent le même intermédiaire diène, préparé très efficacement à partir d'une octalone énantiopure obtenue par cyclisation asymétrique catalysée par la L-phénylalanine. L'acide barbacénique a ainsi pu être obtenu avec un contrôle total de la stéréochimie de ces centres stéréogènes. Un autre bisnorditerpène, l'acide désoxybarbacénique, isolé de la même plante et possédant le même squelette carboné a également été synthétisé permettant ainsi de confirmer sa stéréochimie et sa structure.GRENOBLE1-BU Sciences (384212103) / SudocSudocFranceF

Modulation of (-)-epicatechin metabolism by coadministration with other polyphenols in caco-2 cell model

Widely consumed beverages such as red wine, tea, and cocoaderived products are a great source of flavanols. Epidemiologic and interventional studies suggest that cocoa flavanols such as (- )-epicatechin may reduce the risk of cardiovascular diseases. The interaction of ( - )-epicatechin with food components including other polyphenols could modify its absorption, metabolism, and finally its bioactivity. In the present study we investigate (- )-epicatechin absorption and metabolism when coexposed with other polyphenols in the intestinal absorptive Caco-2 cell model. Depending on the type of polyphenols coadministered, the total amount of 39-O-methyl-epicatechin and 3 ′- O-sulfate-epicatechin conjugates found both in apical and basal compartments ranged from 19 to 801 nM and from 6 to 432 nM, respectively. The coincubation of ( - )-epicatechin with flavanols, chlorogenic acid, and umbelliferone resulted in similar amounts of 3′-O-methyl-epicatechin effluxed into the apical compartment relative to control. Coincubation with isorhamnetin, kaempferol, diosmetin, nevadensin, chrysin, equol, genistein, and hesperitin promoted the transport of 3′-O-methyl-epicatechin toward the basolateral side and decreased the apical efflux. Quercetin and luteolin considerably inhibited the appearance of this ( - )-epicatechin conjugate both in the apical and basolateral compartments. In conclusion, we could demonstrate that the efflux of ( - )-epicatechin conjugates to the apical or basal compartments of Caco-2 cells is modulated by certain classes of polyphenols and their amount. Ingesting ( - )-epicatechin with specific polyphenols could be a strategy to increase the bioavailability of (-)-epicatechin and to modulate its metabolic profile

Synthesis, identification and quantification of oligomers from polyester coatings for metal packaging

Polyester can coatings protect both food and packaging from mutual contamination. Even though, can coatings may release Non-Intentionally Added Substances (NIAS) in addition to Intentionally Added Substances (IAS). As NIAS are mainly constituted by cyclic or linear side products that are formed during the polymerization process, we focused our attention on these oligomeric species of molecular weight <1000 Da. These oligomers were obtained from two different polyester resins, each synthesized from four monomers (two phthalic acids and two diols), and from the corresponding final enamel can coatings using ethanol at 95% and 50% at 60 degrees C for 4 h and 10 days, respectively, as food simulants. HPLC-ESI-MS analysis on the extracts allowed identifying various cyclic and linear oligomers. For the conclusive identification of the different oligomers and their isomeric structures, ad hoc standards were synthesized by acylation reaction between alkyl diols and phthaloyl chlorides. By comparison of H-1 NMR spectra, linear and cyclic oligomers were characterized by finding the major presence of 2 + 2 cyclic compounds. The 16 synthesized standards, 4 linear and 12 cyclic compounds were used to establish a method for quantification of linear and cyclic oligomers in enamel migration samples by micro HPLC-high-resolution MS (HRMS). The results showed no significant differences between the amounts of cyclic oligomers extracted with both ethanol concentrations (50 and 95%) and time contact. The extracts showed only a small amount of linear compounds and a prevalence of 2 + 2 cyclic oligomers. The work shows the great importance of the synthesis of specific standards to allow exact quantification in food contact material migrate

Inter-Laboratory Study to Assess the Consistency of Biological and Chemical Methods to Assess the Safety of Packaging Materials

According to European regulations, migration from food packaging must be safe. However, currently, there is no consensus on how to evaluate its safety, especially for non-intentionally added substances (NIAS). The intensive and laborious approach, involving identification and then quantification of all migrating substances followed by a toxicological evaluation, is not practical or feasible. In alignment with the International Life Sciences Institute (ILSI) and the European Union (EU) guidelines on packaging materials, efforts are focused on combining data from analytics, bioassays and in silico toxicology approaches for the risk assessment of packaging materials. Advancement of non-targeted screening approaches using both analytical methods and in vitro bioassays is key. A protocol was developed for the chemical and biological screening of migrants from coated metal packaging materials. This protocol includes guidance on sample preparation, migrant simulation, chemical analysis using liquid chromatography (LC-MS) and validated bioassays covering endocrine activity, genotoxicity and metabolism-related targets. An inter-laboratory study was set-up to evaluate the consistency in biological activity and analytical results generated between three independent laboratories applying the developed protocol and guidance. Coated packaging metal panels were used in this case study. In general, the inter-laboratory chemical analysis and bioassay results displayed acceptable consistency between laboratories, but technical differences led to different data interpretations (e.g., cytotoxicity, cell passages, chemical analysis). The study observations with the greatest impact on the quality of the data and ultimately resulting in discrepancies in the results are given and suggestions for improvement of the protocol are made (e.g., sample preparation, chemical analysis approaches). Finally, there was agreement on the need for an aligned protocol to be utilized by qualified laboratories for chemical and biological analyses, following best practices and guidance for packaging safety assessment of intentionally added substances (IAS) and NIAS to avoid inconsistency in data and the final interpretation

Japon

Ce numéro de Perspective entend rendre compte de la richesse des études et des travaux que suscitent la création artistique et le patrimoine japonais. Loin de toute approche endogène ou essentialiste, il s’agit de considérer la thématique au-delà des frontières géographiques de l’archipel et de l’envisager à l’aune des dynamiques d’interactions économiques, culturelles et artistiques entretenues avec le reste du monde, les récits et les imaginaires qu’elle a nourris. La revue fait ainsi état de l’actualité de la discipline de l’histoire de l’art au Japon en proposant des grands débats portant sur les Jōmon, la question de la restauration des monuments historiques, ou encore sur les îles musées et les triennales d’art contemporain. Fidèle à sa ligne éditoriale, la revue ouvre ses pages à des contributions couvrant l’ensemble du spectre chronologique, traitant tant des cosmologies bouddhiques à l’époque médiévale, que de la construction de l’historiographie des avant-gardes, en passant par le renouveau des études sur la peinture populaire et les estampes érotiques, le marché de l’art, ou encore le jardin comme objet de déconstruction des stéréotypes de la culture japonaise. Ce numéro est en vente sur le site du Comptoir des presses d'universités. Comité de rédaction du volume Claire-Akiko Brisset, Hélène Bayou, Philippe Bonnin, Jean-Michel Butel, Mathieu Capel, Jean-Sébastien Cluzel, Michael Lucken, Matthew McKelway, Christophe Marquet, Christian Merlhiot, Manuela Moscatiello, Laurent Nespoulous, Sylviane Pagès, Mary Picone, Julien Rousseau, Cécile Sakai, Marie-Anne Sarda, Veerle Thielemans, Clélia Zerni