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International audience; Sore throat is one of the most common reasons for consultation in general medicine. Besides the usual allopathic drugs, phytotherapy can be envisaged for its management. To assess the relevance of a product combining extracts of sage and elder, peppermint essential oil, honey and zinc for the management of sore throat, its effect was evaluated in vitro against the main pathogens involved in sore throat (broth microdilution method) and in a prospective observational study carried out in pharmacies. Bactericidal activity was observed against all Gram-negative (Branhamella catarrhalis, Fusobacterium nucleatum and Haemophilus influenzae) and Gram-positive (Streptococcus pyogenes) bacteria strains; antiviral activity was also tested against type 3 para-influenzae virus. Product activity was maintained at 1:64 dilution ratio. Data collected during the observational study suggest that the product can relieve pain and other symptoms such as dry throat sensation and erythema within 17 minutes on average after spraying. While eliminating possible pathogens involved, the product could relieve pain and symptoms associated with sore throat. These results will have to be confirmed in a clinical trial.; Le mal de gorge est un des motifs de consultation en médecine générale les plus fréquents. Pour le soulager, outre les traitements allopathiques usuels, la prise de produits de phytothérapie peut être envisagée. L’intérêt d’un produit de phytothérapie associant des extraits de sauge et de sureau, de l’huile essentielle de menthe poivrée, du miel et du zinc dans la prise en charge du mal de gorge a été évalué in vitro en mesurant son activité sur les principaux pathogènes impliqués dans les angines (microméthode en milieu liquide) et au cours d’une enquête observationnelle prospective conduite en pharmacie d’officine. Une activité bactéricide a été observée à la fois sur les bactéries à Gram négatif (Branhamella catarrhalis, Fusobacterium nucleatum et Haemophilus influenzae) et à Gram positif (Streptococcus pyogenes) étudiées ainsi qu’une activité antivirale vis à-vis du virus para-influenzae de type 3. Cette activité a été maintenue après dilution du produit au 1/64. Les données recueillies au cours de l’étude observationnelle suggèrent que le produit de phytothérapie peut soulager le mal de gorge et les symptômes associés en particulier la sensation de gorge sèche et l’érythème dans un délai de 17 minutes en moyenne après pulvérisation du produit. Tout en éliminant les éventuels pathogènes impliqués, le produit de phytothérapie pourrait donc soulager la douleur et les symptômes associés au mal de gorge. Ces résultats devront être confirmés au cours d’une étude clinique.

International audience; SCOPE: Targeting gut microbiota dysbiosis by prebiotics is effective, though side-effects such as abdominal bloating and flatulence may arise following high prebiotic consumption over weeks. Our aim was therefore to optimize the current protocol for prebiotic use. METHODS AND RESULTS: To examine the prebiotic properties of plant extracts, we conducted two independent studies in ob/ob mice, over two weeks. In the first study, we evaluated Porphyra umbilicalis and Melissa officinalis L. extracts; in the second study, we assessed a high- vs. low-dose of an Emblica officinalis Gaertn extract. These plant extracts affected gut microbiota, caecum metabolome and induced a significant lower plasma triacylglycerols (TG) following the treatment with P. umbilicalis and significant higher plasma free fatty acids (FFA) following treatment with the low-dose of E. officinalis Gaertn. Glucose- and insulin-tolerance were not affected but white adipose tissue and liver gene expression were modified. In the first study, IL-6 hepatic gene expression was significantly (adjusted P = 0.0015) and positively (r = 0.80) correlated with the bacterial order Clostridiales in all mice. CONCLUSION: Our data show that a 2-week treatment with plant extracts affects the dysbiotic gut microbiota and changes both caecum metabolome and markers of lipid metabolism in ob/ob mice.

International audience; Increasing evidence suggests that polyphenols have a significant potential in the prevention and treatment of risk factors associated with metabolic syndrome. The objective of this study was to assess the metabolic outcomes of two polyphenol-containing extracts from cinnamon bark (CBE) and grape pomace (GPE) on C57BL/6J mice fed a high-fat diet (HFD) for 8 weeks. Both CBE and GPE were able to decrease fat mass gain and adipose tissue inflammation in mice fed a HFD without reducing food intake. This was associated with reduced liver steatosis and lower plasma non-esterified fatty acids levels. We also observed a beneficial effect on glucose homeostasis as evidenced by an improved glucose tolerance and a lower insulin resistance index. These ameliorations of the overall metabolic profile were associated to a significant impact on the microbial composition, which was more profound for the GPE than for the CBE. At the genus level, Peptococcus were decreased in the CBE group. In the GPE treated group, several key genera that have been previously found to be linked with HFD, metabolic effects and gut barrier integrity were affected: we observed a decrease of Desulfovibrio, Lactococcus, whereas Allobaculum and Roseburia were increased. In addition, the expression of several antimicrobial peptides and tight junction proteins was increased in response to both CBE and GPE supplementation, indicating an improvement of the gut barrier function. Collectively, these data suggest that CBE and GPE can ameliorate the overall metabolic profile of mice on a high-fat diet, partly by acting on the gut microbiota.

Introduction et but de l’etude Plusieurs etudes precliniques et cliniques ont montre les benefices de la consommation de polyphenols, notamment dans la prevention du syndrome metabolique et de ses facteurs de risques associes comme l’obesite et le diabete. Cependant, peu de donnees sont disponibles concernant l’impact des polyphenols sur le microbiote intestinal et les facteurs de risques cardiometaboliques. L’objectif de notre etude a ete d’evaluer les effets de deux extraits vegetaux riches en polyphenols (cannelle et marc de raisin) sur le metabolisme, le microbiote intestinal et la barriere intestinale. Materiel et methodes Des souris C57BL/6 mâles âgees de neuf semaines ont ete nourries pendant huit semaines avec un regime controle (CT), un regime riche en graisses (HFD), ou un regime riche en graisses apportant un extrait de cannelle (CBE) ou un extrait de marc de raisin (GPE) (14 souris/groupe). Le poids et la prise alimentaire ont ete mesures chaque semaine et la composition corporelle estimee par RMN. A sept semaines, une epreuve d’hyperglycemie provoquee par voie orale a ete realisee. A la fin du suivi, des selles ont ete collectees pour l’analyse du microbiote intestinal et calorimetrie indirecte. Dans chaque groupe, neuf souris ont ete sacrifiees pour isoler et analyser leurs tissus et les 5 autres souris ont ete passees en cages metaboliques pour evaluer leur depense energetique et activite physique. Resultats et analyse statistique La consommation des deux extraits etudies (CBE et GPE) associe au regime HFD a diminue la prise de masse grasse et reduit l’inflammation du tissu adipeux generalement induites par le regime riche en graisse, sans impacter la consommation alimentaire, ni la quantite d’energie excretee dans les matieres fecales. Ces effets etaient associes a une reduction de la steatose hepatique et une diminution des taux d’acides gras libres circulants. L’homeostasie du glucose a egalement ete amelioree (amelioration de la tolerance au glucose et une reduction de l’insulino-resistance). Par ailleurs, l’amelioration du profil metabolique observee apres consommation des deux extraits vegetaux etait associee a un effet significatif sur la composition du microbiote intestinal, notamment pour le groupe GPE. Dans le groupe GPE, une diminution des Desulfovibrio et Lactococcus, et une augmentation des Allobaculum et Roseburia ont ete observees. Enfin, l’expression de plusieurs peptides antimicrobiens et proteines de jonctions serrees a ete augmentee dans les groupes CBE et GPE, indiquant une amelioration de la fonction de barriere de la muqueuse intestinale. Conclusion Nos resultats suggerent que les extraits de cannelle et de marc de raisin testes peuvent ameliorer le profil metabolique de souris recevant un regime riche en graisse, en agissant notamment sur le microbiote intestinal.

Alterations of the microtubule network, which is involved in many vital processes, occur in several pathological conditions, such as cardiac ischemia. However, the connection between the microtubule assembly state and the factors affecting myocardial reperfusion injury, especially oxidative stress, is unknown. We aimed thus to study the effects of different tubulin ligands on the changes in the microtubule network and in several markers of cell injury and oxidative activity in cardiac muscle cells submitted to a reversible substrate-free, hypoxia-reoxygenation model of ischemia-reperfusion. The microtubule network was visualized by immunocytochemistry. Cell injury was evaluated via lactate dehydrogenase release and the mitochondrial function by the MTT test. Superoxide production was detected using dihydroethidium. The activity of NADPH oxidase and mRNA subunit expression were investigated. The microtubule disassembly induced by simulated ischemia was reversed by placing cardiomyocytes under normoxic conditions. This post-"ischemic" restoration of microtubule assembly was modulated by microtubule stabilizers (taxol: paclitaxel) and by microtubule disrupting drugs (nocodazole, colchicine). In addition, nocodazole decreased superoxide anion production as well as NADPH oxidase activity and mRNA expression of the NADPH oxidase subunit p22phox. These results demonstrated that the "ischemia"-induced microtubule network alteration is reversible and suggest a possible relationship between "reperfusion"-induced reassembly of microtubules and free radical generation in post-"ischemic" cardiomyocytes.

International audience; New agents that are effective against common pathogens are needed particularly for those resistant to conventional antimicrobial agents. Essential oils (EOs) are known for their antimicrobial activity. Using the broth microdilution method, we showed that (1) two unique blends of Cinnamomum zeylanicum, Daucus carota, Eucalyptus globulus and Rosmarinus officinalis EOs (AB1 and AB2; cinnamon EOs from two different suppliers) were active against the fourteen Gram‐positive and ‐negative bacteria strains tested, including some antibiotic‐resistant strains. Minimal inhibitory concentrations (MICs) ranged from 0.01% to 3% v/v with minimal bactericidal concentrations from

Background Preventing or slowing the progression of prediabetes to diabetes is a major therapeutic issue. Objectives Our aim was to evaluate the effects of 4-month treatment with a dietary supplement containing cinnamon, chromium and carnosine in moderately obese or overweight pre-diabetic subjects, the primary outcome being change in fasting plasma glucose (FPG) level. Other parameters of plasma glucose homeostasis, lipid profile, adiposity and inflammatory markers were also assessed. Methods In a randomized, double-blind, placebo-controlled study, 62 subjects with a FPG level ranging from 5.55 to 7 mmol/L and a body mass index ≥25 kg/m2, unwilling to change their dietary and physical activity habits, were allocated to receive a 4-month treatment with either 1.2 g/day of the dietary supplement or placebo. Patients were followed up until 6 months post-randomization. Results Four-month treatment with the dietary supplement decreased FPG compared to placebo (-0.24±0.50 vs +0.12±0.59 mmol/L, respectively, p = 0.02), without detectable significant changes in HbA1c. Insulin sensitivity markers, plasma insulin, plasma lipids and inflammatory markers did not differ between the treatment groups. Although there were no significant differences in changes in body weight and energy or macronutrient intakes between the two groups, fat-free mass (%) increased with the dietary supplement compared to placebo (p = 0.02). Subjects with a higher FPG level and a milder inflammatory state at baseline benefited most from the dietary supplement. Conclusions Four-month treatment with a dietary supplement containing cinnamon, chromium and carnosine decreased FPG and increased fat-free mass in overweight or obese pre-diabetic subjects. These beneficial effects might open up new avenues in the prevention of diabetes. Trial Registration ClinicalTrials.gov NCT01530685

Defining the substrate that influences the most favourably the myocardial post-ischemic recovery is subject of debates, due to dissociation between functional and biochemical benefits. Hence, we studied the effects of either glucose or different fatty acids on the functional and metabolic recovery of post-ischemic cardiomyocytes in a substrate-free hypoxia model of simulated ischemia-reperfusion. Rat cardiomyocytes were submitted to a 2.5 h simulated ischemia followed by a 2 h reoxygenation without substrate (control), or with either glucose, octanoic acid, oleic acid, or elaidic acid. During simulated ischemia, electromechanical function gradually disappeared while the cellular viability and mitochondrial function declined. During control simulated reperfusion, cardiomyocytes recovered near normal function but a significant reduction in the action potential amplitude and rate persisted. The addition of glucose or oleic acid during simulated reperfusion promoted a faster, better and sustain functional recovery. Amongst the fatty acids, the functional recovery was slower with elaidic and octanoic acids as compared with oleic acid. The mitochondrial function was better improved during simulated reperfusion with glucose than with the tested fatty acids, among which elaidic acid was the less unfavourable. Paradoxically, the addition of whichever substrate during simulated reperfusion tended to worsen the cellular viability. Thus, cardiomyocytes recovery strongly relies on the characteristics of the substrate supplied at the onset of simulated reperfusion: glucidic or lipidic nature, chain-length, insaturation degree. Moreover, these data suggest that defining the appropriateness of a given substrate for the post-ischemic cardiomyocyte recovery is closely related to the functional and the biological endpoints in consideration.

Cyclosporin A is an immunosuppressor that prolongs graft survival but its use is limited by cardiotoxicity. The effects of cyclosporin A on several functional and biological characteristics were thus evaluated in rat cardiomyocytes in normal conditions and in a substrate-free, hypoxia–reoxygenation model of ischemia–reperfusion. Cyclosporin A (100 and 1000 ng/ml) did not induce cardiocytotoxicity in basal conditions. Simulated ischemia gradually decreased and then blocked the spontaneous electromechanical activity. Cyclosporin A at 100 and 1000 ng/ml permitted the maintenance of electromechanical functions that were abolished in control cells. Cyclosporin A also improved the post-“ischemic” functional recovery. Cyclosporin A reduced the “ischemia”-induced lactate dehydrogenase and troponine I releases and the successive rises in heat shock protein mRNA observed after “ischemia” and reoxygenation. Moreover, cyclosporin A improved the resumption of the mitochondrial function. To conclude, cyclosporin A displayed a direct, pleiotropic protection of isolated cardiomyocytes against physiological, metabolic, structural and stress signaling changes induced by ischemia–reperfusion mimicked in vitro.

Background Previous work showed that the functional cardiac effect of dietary alpha-linolenic acid (ALA) in rats requires a long feeding period (6 months), although a docosahexaenoic (DHA) acid-supply affects cardiac adrenergic response after 2 months. However, the total cardiac membrane n-3 polyunsaturated fatty acid (PUFA) composition remained unchanged after 2 months. This delay could be due to a specific reorganization of the different subcellular membrane PUFA profiles. This study was designed to investigate the evolution between 2 and 6 months of diet duration of the fatty acid profile in sarcolemmal (SL), mitochondrial (MI), nuclear (NU) and sarcoplasmic reticulum (SR) membrane fractions. Methods Male Wistar rats were randomly assigned to 3 dietary groups (n = 10/diet/period), either n-3 PUFA-free diet (CTL), or ALA or DHA-rich diets. After 2 or 6 months, the subcellular cardiac membrane fractions were separated by differential centrifugations and sucrose gradients. Each membrane profile was analysed by gas chromatography (GC) after lipid extraction. Results As expected the n-3 PUFA-rich diets incorporated n-3 PUFA instead of n-6 PUFA in all the subcellular fractions, which also exhibited individual specificities. The diet duration increased SFA and decreased PUFA in SL, whereas NU remained constant. The SR and MI enriched in n-3 PUFA exhibited a decreased DHA level with ageing in the DHA and CTL groups. Conversely, the n-3 PUFA level remained unchanged in the ALA group, due to a significant increase in docosapentaenoic acid (DPA). N-3 PUFA rich diets lead to a better PUFA profile in all the fractions and significantly prevent the profile modifications induced by ageing. Conclusion With the ALA diet the n-3 PUFA content, particularly in SR and SL kept increasing between 2 and 6 months, which may partly account for the delay to achieve the modification of adrenergic response.