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Productions scientifiques

2017, ICR-2010-2017.

ACL - Articles dans des revues à comité de lecture

6 références.
2017


  • Alezra, V.; Wan, Y.; Auberger, N.; Thétiot-Laurent, S.; Bouillère, F.; Zulauf, A.; He, J.; Courtiol-Legourd, S.; Guillot, R.; Kouklovsky, C.; Cote des Combes, S.; Pacaud, C.; Devillers, I. European Journal of Organic Chemistry 2017.
    Résumé : We describe here an efficient synthesis of both diastereomers of cyclic b,g-diamino acids starting from L-glutamic acid based on Blaise reaction. We showed that by changing the protecting group, we could have access to either 5-member ring lactam, which can be used as b-amino acid, or to 6-member ring lactam, as g-amino acid. We also discovered an interesting kinetic resolution during the synthesis which allowed easier diastereomer separation. These compounds can be easily used in peptide synthesis and a tetramer alternating trans cyclic g-amino acid and AIB has been synthesized.


  • Kandouli, C.; Cassien, M.; Mercier, A.; Delehedde, C.; Ricquebourg, E.; Stocker, P.; Mekaouche, M.; Leulmi, Z.; Mechakra, A.; Thétiot-Laurent, S.; Culcasi, M.; Pietri, S. Journal of Ethnopharmacology 2017.
    Résumé : Ethnopharmacological relevance According to Saharian traditional medicine, Anvillea radiata Coss. & Dur. (Asteraceae) has been valued for treating a variety of ailments such as gastro-intestinal, liver and pulmonary diseases, and has gained awareness for its beneficial effect on postprandial hyperglycemia. However, to best of our knowledge, no detailed study of the antidiabetic curative effects of this plant has been conducted yet. Aim of the study To determine the hypoglycemic and antidiabetic effect of dietary supplementation with Anvillea radiata extracts on high-fat-diet (HFD)-induced obesity and insulin resistance in C57BL/6 J mice in relation with antioxidant, anti-inflammatory, pancreatic beta-cells and skeletal muscle protection, and digestive enzyme inhibiting properties. Materials and methods Six extracts (water soluble and organic) from aerial parts of the plant were analyzed phytochemically (total phenolic and flavonoid content) and screened for in vitro superoxide (by chemiluminescence) and hydroxyl radical (by electron paramagnetic resonance spin-trapping) scavenging, antioxidant (DPPH, TRAP and ORAC assays), xanthine oxidase, metal chelating, α-amylase and α-glucosidase inhibitory property, and protective effects on copper-induced lipoprotein oxidation. Then selected hydroalcoholic and aqueous extracts were assessed for toxicity in normal human lung fibroblasts and A549 cancer cells using FMCA and MTT assays. Two water-soluble extracts having the best overall properties were assessed for their (i) protective effect at 1−15 µg/mL on metabolic activity of rat insulinoma-derived INS-1 cells exposed to hyperglycemic medium, and (ii) acute hypoglycemic effect on 16-weeks HFD-induced diabetic mice. Then diabetic mice were administered HFD supplemented by extracts (up to 150 mg/kg/day) for 12 additional weeks using standard diet as control and the antidiabetic drug, metformin (150 mg/kg), as positive control. Then the antidiabetic, anti-inflammatory and antioxidant activity of extracts were determined. Results Of the highly efficient polyphenolics-enriched hydroalcoholic and ethyl acetate extracts, the lyophilized aqueous (AQL) and butanol extracts were not toxic in cells (≤ 400 µg/mL) or when given orally in normal mice (≤ 2000 mg/kg), exerted a dose-dependent hypoglycemic action in diabetic mice, which was maximal at the dose of 150 mg/kg. Upon administering this dose for 12 weeks, both extracts significantly ameliorated body weight control capacity, recovery of plasma glucose and insulin level, reduced oxidative stress in blood, myocardial and skeletal muscles, and improved hyperlipidemic and inflammatory status. Moreover, diabetes-related complications were optimally ameliorated by oral therapy based on halved doses (75 mg/kg) of a mixture of AQL and metformin. Conclusions Current investigation supports the traditional medicinal usage of Anvillea radiata and suggests that both readily accessible and low-cost bio-extracts have the potency to develop an antihyperglycemic, antihyperlipidemic and protective agent against beta-cells and muscle dysfunction at doses compatible with the common practices of indigenous people for the management of metabolic disorders.


  • Mousslim, M.; Pagano, A.; Andreotti, N.; Garrouste, F.; Thuault, S.; Peyrot, V.; Parat, F.; Luis, J.; Culcasi, M.; Thétiot-Laurent, S.; Pietri, S.; Sabatier, J. - M.; Kovacic, H. European Journal of Pharmacology 2017, 794, 162-172.
    Résumé : The NADPH oxidase proteins catalyse the formation of superoxide anion which act as signalling molecules in physiological and pathological processes. Nox1-dependent NADPH oxidase is expressed in heart, lung, colon, blood vessels and brain. Different strategies involving Nox1 inhibition based on diphenylene iodonium derivatives are currently tested for colorectal cancer therapy. Here, after peptides screening on Nox1-dependent NADPH oxidase assay in HT-29 cells, we identify a peptide (referred to as NF02), cell-active, that potently block Nox1-dependent reactive oxygen species generation. Study of DEPMPO adduct formation by electron paramagnetic resonance showed that NF02 has no superoxide scavenging activity and no impact on cellular reactive oxygen species-producing enzymes such xanthine oxidase. NF02 was not cytotoxic, inhibited reactive oxygen species production of reconstituted Nox1/Noxo1/Noxa1 complex in HEK293 and did not decrease Nox2 dependent cellular NADPH oxidase reactive oxygen species production. Finally, NF02 inhibited cell migration and invasion of colorectal cancer cells which is consistent with the described impact of Nox1 inhibitors on cell migration. NF02 peptide is a new NADPH oxidase inhibitor specific for Nox1 over Nox2 and xanthine oxidase which might represent a useful Nox1 tool with potential therapeutic insights.


  • Stocker, P.; Cassien, M.; Vidal, N.; Thétiot-Laurent, S.; Pietri, S. Talanta 2017.
    Résumé : Myeloperoxidase (MPO) is a key enzyme derived from leukocytes which is associated with the initiation and progression of many inflammatory diseases. Increased levels of MPO may contribute to cellular dysfunction and tissues injury by producing highly reactive oxidants such as hypochlorous acid (HOCl). Myeloperoxidase-generated HOCl is therefore considered as a relevant biomarker of oxidative stress-related damage and its quantitation is of great importance to the study of disease progression. In this context, the current study describes a rapid, sensitive and homogeneous fluorescence-based method for detecting the MPO chlorination activity in biological samples. This assay utilizes 7-hydroxy-2-oxo-2H-chromene-8-carbaldehyde oxime as a selective probe for HOCl detection, and is adapted to 96-well microplates to allow high-throughput quantitation of active MPO. The ability of the method to monitor HOCl release was further investigated in hyperglycemic streptozotocin-treated diabetic rats. The data proved that the present assay has a reliable performance when quantitating the active MPO in the plasma of diabetic animals, a feature of inflammatory disease found concomitant with an elevation of protein carbonyls levels and lipid peroxidation and which was negatively correlated with the ratio of reduced-to-oxidized glutathione.


  • Thétiot-Laurent, S.; Gosset, G.; Clément, J. - L.; Cassien, M.; Mercier, A.; Siri, D.; Gaudel-Siri, A.; Rockenbauer, A.; Culcasi, M.; Pietri, S. ChemBioChem 2017, 18 (3), 300-315.
    Résumé : There is increasing interest in measuring pH in biological samples by using nitroxides with pH-dependent electron paramagnetic resonance (EPR) spectra. Aiming to improve the spectral sensitivity (ΔaX) of these probes (i.e., the difference between the EPR hyperfine splitting (hfs) in their protonated and unprotonated forms), we characterized a series of novel linear α-carboxy, α′-diethoxyphosphoryl nitroxides constructed on an amino acid core and featuring an (α or α′)-C−H bond. In buffer, the three main hfs (aN, aH, and aP) of their EPR spectra vary reversibly with pH and, from aP or aH titration curves, a two- to fourfold increase in sensitivity was achieved compared to reference imidazoline or imidazolidine nitroxides. The crystallized carboxylate 10 b (pKa ≈3.6), which demonstrated low cytotoxicity and good resistance to bioreduction, was applied to probe stomach acidity in rats. The results pave the way to a novel generation of highly sensitive EPR pH markers.


  • Tranchida, F.; Rakotoniaina, Z.; Shintu, L.; Tchiakpe, L.; Deyris, V.; Yemloul, M.; Stocker, P.; Vidal, N.; Rimet, O.; Hiol, A.; Caldarelli, S. Scientific Reports 2017, 7 (1).
    Résumé : The metabolic effects of an oral supplementation with a Curcuma longa extract, at a dose nutritionally relevant with common human use, on hepatic metabolism in rats fed a high fructose and saturated fatty acid (HFS) diet was evaluated. High-resolution magic-angle spinning NMR and GC/MS in combination with multivariate analysis have been employed to characterize the NMR metabolite profiles and fatty acid composition of liver tissue respectively. The results showed a clear discrimination between HFS groups and controls involving metabolites such as glucose, glycogen, amino acids, acetate, choline, lysophosphatidylcholine, phosphatidylethanolamine, and β-hydroxybutyrate as well as an increase of MUFAs and a decrease of n-6 and n-3 PUFAs. Although the administration of CL did not counteract deleterious effects of the HFS diet, some metabolites, namely some n-6 PUFA and n-3 PUFA, and betaine were found to increase significantly in liver samples from rats having received extract of curcuma compared to those fed the HFS diet alone. This result suggests that curcuminoids may affect the transmethylation pathway and/or osmotic regulation. CL extract supplementation in rats appears to increase some of the natural defences preventing the development of fatty liver by acting on the choline metabolism to increase fat export from the liver.