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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; A multispecies Lactobacillus- and Bifidobacterium-containing probiotic mixture significantly reduced the adverse metabolic and inflammatory effects of a 14-week high-fat diet in wild-type C57/BL6J mice gavaged 5 days a week with the probiotic mixture or vehicle. Recent evidence indicates that the gut microbiome may play a decisive role in the onset of obesity and associated chronic metabolic diseases, such as type 2 diabetes, by modulating nutrient absorption and factors conducive to development of a persistent low-grade inflammatory state. By modifying the gut microbiome, probiotics might constitute an effective dietary strategy for managing these metabolic disorders. The tested probiotic mixture significantly attenuated the increase in body weight, serum glucose concentration and insulin resistance induced by the high-fat diet. Furthermore, it significantly reduced the up-regulation of expression of several genes encoding pro-inflammatory adipokines and leukotriene pathway enzymes (CCL-2, IL-6 and leukotriene C4 synthase in adipose tissue, leukotriene C4 synthase and leukotriene A4 hydrolase in the gut). It also significantly counteracted the down-regulation of adipose tissue gene expression related to the anti-inflammatory adipokine adiponectin in mice fed the high-fat diet. These results suggest that the mechanism underlying the beneficial metabolic effects of the probiotic mixture might involve inhibition of gut and adipose tissue inflammation.

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

A link between telomere shortening and oxidative stress was found in aging people and patients with cancer or inflammatory diseases. Extracts of Astragalus spp. are known to stimulate telomerase activity, thereby compensating telomere shortening. We characterized a multi-component hydroethanolic root extract (HRE) of Astragalus mongholicus Bunge and assessed its effects on telomeres compared to those of danazol. Astragalosides I to IV, flavonoids, amino acids and sugars were detected in the HRE. Samples of peripheral blood lymphocytes with short telomeres from 18 healthy donors (mean age 63.5 years, range 3286 years) were exposed to a single dose of 1 &micro, g/mL HRE or danazol for three days. Telomere length and telomerase expression were then measured. Significant elongation of telomeres associated to a less toxicity was observed in lymphocytes from 13/18 donors following HRE treatment (0.54 kb (0.15&ndash, 2.06 kb)) and in those from 9/18 donors after danazol treatment (0.95 kb (0.06&ndash, 2.06 kb)). The rate of cells with short telomeres (&lt, 3 kb) decreased in lymphocytes from all donors after exposure to either HRE or danazol, telomere elongation being telomerase-dependent. These findings suggest that the HRE could be used for the management of age-related diseases.

International audience; A role of the gut microbiota in psychiatric disorders is supported by a growing body of literature. The effects of a probiotic mixture of four bacterial strains were studied in two models of anxiety and depression, naturally stress-sensitive Fischer rats and Long Evans rats subjected to maternal deprivation. Rats chronically received either the probiotic mixture (1.10(9) CFU/day) or the vehicle. Anxiety- and depressive-like behaviors were evaluated in several tests. Brain monoamine levels and gut RNA expression of tight junction proteins (Tjp) and inflammatory markers were quantified. The gut microbiota was analyzed in feces by 16S rRNA gene sequencing. Untargeted metabolite analysis reflecting primary metabolism was performed in the cecal content and in serum. Fischer rats treated with the probiotic mixture manifested a decrease in anxiety-like behaviors, in the immobility time in the forced swimming test, as well as in levels of dopamine and its major metabolites, and those of serotonin metabolites in the hippocampus and striatum. In maternally deprived Long Evans rats treated with the probiotic mixture, the number of entries into the central area in the open-field test was increased, reflecting an anxiolytic effect. The probiotic mixture increased Tjp1 and decreased Ifn gamma mRNA levels in the ileum of maternally deprived rats. In both models, probiotic supplementation changed the proportions of several Operational Taxonomic Units (OTU) in the gut microbiota, and the levels of certain cecal and serum metabolites were correlated with behavioral changes. Chronic administration of the tested probiotic mixture can therefore beneficially affect anxiety- and depressive-like behaviors in rats, possibly owing to changes in the levels of certain metabolites, such as 21-deoxycortisol, and changes in brain monoamines.

International audience; The aim of this study was to carry out HPTLC (high-performance thin-layer chromatography) fingerprinting analysis and to identify by LC/MS (liquid chromatography– mass spectrometry) the main components of a hydroethanolic extract of cypress (Cupressus sempervirensL.) fresh cones; the study also aimed at evaluating the extract’s virucidal activity against four human viruses and three bovine viruses. The phytochemical analysis showed the presence of tannins, flavonoids, amino acids, and carbohydrates. At 40% (v/v) concentration, in contact with viruses for 60 minutes at 37 °C, the extract had virucidal activity against coronavirus, parainfluenza type 3 virus, bovine respiratory syncytial virus, and bovine rotavirus. At 80% (v/v), the extract had virucidal activity against influenza A-H1N1 virus, rhinovirus, and bovine herpes type 1 virus. These results show that it would be worthwhile to pursue research on this cypress extract and to explore its antiviral effects in vivo.

Valeriana officinalis L. root extracts are traditionally taken for their sedative and anxiolytic properties and are also used for muscle relaxation. Relaxant effects were clearly observed on smooth muscle whereas data on effects on skeletal muscle are scarce and inconsistent. The aim of this study was to assess whether a standardized extract (SE) of V. officinalis had myorelaxant effects by decreasing skeletal muscle strength and/or neuromuscular tone in mice. Mice received an acute dose of V. officinalis SE (2 or 5 g/kg per os) or tetrazepam (10 mg/kg ip), a standard myorelaxant drug. Thirty minutes later, the maximal muscle strength was measured using a grip test, while global skeletal muscle function (endurance and neuromuscular tone) was assessed in a wire hanging test. Compared to tetrazepam, both doses of V. officinalis SE induced a pronounced decrease in skeletal muscle strength without any significant effects on endurance and neuromuscular tone. This study provides clear evidence that the extract of V. officinalis tested has a relaxant effect on skeletal muscle. By decreasing skeletal muscle strength without impacting endurance and neuromuscular tone, V. officinalis SE could induce less undesirable side effects than standard myorelaxant agents, and be particularly useful for avoiding falls in the elderly. Keywords: Valeriana officinalis, Skeletal muscle relaxant, Strength, Hydroethanolic root extract, Acute treatment, Mouse

Epilepsy is a neurological condition that affects 1% of the world population. Conventional treatments of epilepsy use drugs targeting neuronal excitability, inhibitory or excitatory transmission. Yet, one third of patients presents an intractable form of epilepsy and fails to respond to pharmacological anti-epileptic strategies. The ketogenic diet is a well-established non-pharmacological treatment that has been proven to be effective in reducing seizure frequency in the pharmaco-resistant patients. This dietary solution is however extremely restrictive and can be associated with complications caused by the high [fat]:[carbohydrate + protein] ratio. Recent advances suggest that the traditional 4:1 ratio of the ketogenic diet is not a requisite for its therapeutic effect. We show here that combining nutritional strategies targeting specific amino-acids, carbohydrates and fatty acids with a low [fat]:[proteins + carbohydrates] ratio also reduces excitatory drive and protects against seizures to the same extent as the ketogenic diet. Similarly, the morphological and molecular correlates of temporal lobe seizures were reduced in animals fed with the combined diet. These results provide evidence that low-fat dietary strategies more palatable than the ketogenic diet could be useful in epilepsy.

International audience; Rhodiola rosea L. (R. rosea) is an adaptogenic plant increasing body resistance to stress. Its efficacy has been evidenced mainly in chronic stress models, data concerning its effect in acute stress and underlying mechanisms being scarce. The objective was to investigate the effect of repeated doses of a R. rosea hydroethanolic root extract (HRE) on hypothalamic pituitary adrenal response in a murine model of acute mild stress and also the mechanisms involved. Stress response was measured in Balb/c mice having received by gavage HRE (5 g/kg) or vehicle daily for 2 weeks before being submitted to an acute mild stress protocol (open‐field test then elevated plus maze). Corticosterone was measured in plasma from mandibular vein blood drawn before and 30, 60, and 90 min after initiation of the stress protocol. Mice were sacrificed at 90 min, and the hippocampus, prefrontal cortex, and amygdala were excised for high‐frequency RT‐PCR gene expression analysis. At 30 min after acute mild stress induction, corticosterone level in mice having received the HRE was lower than in control mice and comparable to that in nonstressed mice in the HRE group. HRE administration induced brain structure‐dependent changes in expression of several stress‐responsive genes implicated in neuronal structure, HPA axis activation, and circadian rhythm. In the acute mild stress model used, R. rosea HRE decreased corticosterone level and increased expression of stress‐responsive genes, especially in the hippocampus and prefrontal cortex. These findings suggest that R. rosea HRE could be of value for modulating reactivity to acute mild stress.

International audience; Melissa officinalis L. (lemon balm) has been used for decades with symptomatic benefits in patients with digestive disorders. However, very little is known on the effects of M. officinalis on the gastrointestinal (GI) tract. In this study, the basal and spasmolytic properties of a hydroethanolic leaf extract (HLE) of M. officinalis were assessed ex vivo on different segments of the GI tract of mice after phytochemical characterization of the extract. M. officinalis HLE had site- and dose-dependent effects on the contractile activity of the GI tract, the motility response being impacted in the jejunum and ileum but not in the antrum and colon. The observed effects could be caused by the phenolic compounds (mainly rosmarinic acid) detected in the extract.

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.

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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.

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.

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International audience; Lutein is recovered at high concentration in the human macula lutea. Recent studies suggest that this micronutrient might be implicated in prevention of age-related macular degeneration. Objective. To identify genes which affect blood and retina lutein concentrations among candidate genes (intestinal sterol transporters and carotenoid oxygenases). Design. A comparative plus an observational study. Participants. Twenty-nine healthy subjects for the comparative study and 622 subjects for the observational study. Intervention and methods. All the participants were genotyped for single nucleotide polymorphisms (SNPs) in the candidate genes. Fasting plasma lutein concentrations were measured in all the participants and after 6 months' supplementation, with either a lutein-rich supplement or a placebo, in the 29 subjects who participated in the comparative study. Macular pigment optical density (MPOD), which is a measure of macula concentration of lutein, was measured before and after the dietary intervention in the 29 subjects. Associations between SNPs and plasma lutein and MPOD were assessed by partial least square (PLS) regression followed by univariate analysis. Observed associations between SNPs and plasma lutein were verified by haplotype-based association analysis in the cohort of 622 subjects. Main outcome measures. Plasma lutein levels and MPOD. Results. Six SNPs in four genes (ABCG8, BCMO1, CD36, and NPC1L1) explained 25% and 38% of the plasma and MPOD variance, respectively. Subjects with TT at the BCMO1 rs7501331 locus had lower (P < 0.05) plasma lutein than CT subjects. Subjects with CC at the CD36 rs13230419 locus had lower (P < 0.05) plasma lutein than subjects who carried a T allele. The association between CD36 and plasma lutein was confirmed in the cohort of 622 subjects. Subjects with TT at the BCMO1 rs7501331 locus had a higher (P < 0.05) MPOD, and subjects with GG at rs1761667 CD36 locus had a higher (P < 0.05) MPOD than those with an A allele. Conclusions. These results suggest that BCMO1 and CD36 are implicated in plasma and retina concentrations of lutein and that genetic variants in these genes can modulate blood and retina concentrations of lutein.

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