Search

TOTUM-070 is a patented polyphenol-rich blend of five different plant extracts showing separately a latent effect on lipid metabolism and potential synergistic properties. In this study, we investigated the health benefit of such a formula. Using a preclinical model of high fat diet, TOTUM-070 (3 g/kg of body weight) limited the HFD-induced hyperlipemia with a reduction in triglyceride (−32% after 6 weeks; −20.3% after 12 weeks) and non-HDL cholesterol levels (−21% after 6 weeks; −38.4% after 12 weeks). To further investigate such a benefit and its underlying mechanisms in humans, we designed an ex vivo clinical approach to collect the circulating bioactives resulting from TOTUM-070 ingestion and to determine their biological activities on human hepatocytes. Human serum was obtained from healthy subjects before and after intake of TOTUM-070 (4995 mg). The presence of circulating metabolites was assessed by UPLC-MS/MS. Serum containing metabolites was further incubated with hepatocytes cultured in a lipotoxic environment (palmitate, 250 µM). RNA sequencing analyses show that lipid metabolism was one of the most impacted processes. Using histologic, proteomic, and enzymatic assays, the effects of human TOTUM-070 bioactives on hepatocyte metabolism were characterized by (1) the inhibition of lipid storage, including both (2) triglycerides (−41%, p < 0.001) and (3) cholesterol (−50%, p < 0.001) intracellular content, (4) a reduced de novo cholesterol synthesis (HMG-CoA reductase activity −44%, p < 0.001), and (5) a lowered fatty acid synthase protein level (p < 0.001). Altogether, these data support the beneficial impact of TOTUM-070 on lipid metabolism and provide new biochemical insights in human mechanisms occurring in liver cells.

International audience; Due to its significant exposure to stressful environmental factors, the skin undergoes a high remodeling rate over time, which alters not only its appearance but also its functionality. This alteration of the skin, namely photoaging, is characterized by dryness and a loss of elasticity that mainly originates from the dysregulation of dermal fibroblast activities. In order to overcome such tissue outcome, cosmetic products have evolved toward nutricosmetics, thus promoting beauty from within. Among bio-actives of interest, bio-peptides deriving from plant or animal sources may exert various biological activities beyond their nutritional value. However, studies remain mostly descriptive and the mode of action at the cellular level in clinic remains a concern. In a recent clinical trial, it was showed that supplementation with a fish cartilage hydrolysate (FCH) improved signs of chronological and photoaging-induced skin changes in healthy women. Here, using an original ex vivo clinical approach adapted to nutricosmetic purpose, we further demonstrated that this fish cartilage hydrolysate was absorbed and that the circulating metabolites produced in humans following FCH intake stimulate human dermal fibroblast growth, promote specific hyaluronan production, up-regulate elastin synthesis and inhibit MMP-1 and 3 expression along with the enhancement of TGF-β release. Altogether, these data provide clues on the mechanisms likely contributing to the beneficial impact of FCH on human skin functionality by supporting hydration, elasticity and limiting the expression of catabolic factors involved in photoaging onset.

International audience; The aging of our population is accompanied by an increased prevalence of chronic diseases. Among those, liver, joint and adipose tissue-related pathologies have a major socio-economic impact. They share common origins as they result from a dysregulation of the inflammatory and metabolic status. Plant-derived nutrients and especially polyphenols, exert a large range of beneficial effects in the prevention of chronic diseases but require clinically validated approaches for optimized care management. In this study, we designed an innovative clinical approach considering the metabolites produced by the digestive tract following the ingestion of an artichoke leaf extract. Human serum, enriched with metabolites deriving from the extract, was collected and incubated with human hepatocytes, human primary chondrocytes and adipocytes to determine the biological activity of the extract. Changes in cellular behavior demonstrated that the artichoke leaf extract protects hepatocytes from lipotoxic stress, prevents adipocytes differentiation and hyperplasia, and exerts chondroprotective properties in an inflammatory context. These data validate the beneficial health properties of an artichoke leaf extract at the clinical level and provide both insights and further evidence that plant-derived nutrients and especially polyphenols from artichoke may represent a relevant alternative for nutritional strategies addressing chronic disease issues.

International audience; Increases in oxidative stress have been reported to play a central role in the vulnerability to depression, and antidepressant drugs may reduce increased oxidative stress in patients. Among the plants exerting anti-inflammatory and anti-oxidant properties, saffron, a spice derived from the flower of Crocus sativus, is also known for its positive effects on depression, potentially through its SSRI-like properties. However, the molecular mechanisms underlying these effects and their health benefits for humans are currently unclear. Using an original ex vivo clinical approach, we demonstrated for the first time that the circulating human metabolites produced following saffron intake (Safr’InsideTM) protect human neurons from oxidative-stress-induced neurotoxicity by preserving cell viability and increasing BNDF production. In particular, the metabolites significantly stimulated both dopamine and serotonin release. In addition, the saffron’s metabolites were also able to protect serotonergic tone by inhibiting the expression of the serotonin transporter SERT and down-regulating serotonin metabolism. Altogether, these data provide new biochemical insights into the mechanisms underlying the beneficial impact of saffron on neuronal viability and activity in humans, in the context of oxidative stress related to depression.; Il a été rapporté que l'augmentation du stress oxydatif joue un rôle central dans la vulnérabilité à la dépression, et les antidépresseurs peuvent réduire l'augmentation du stress oxydatif chez les patients. Parmi les plantes exerçant des propriétés anti-inflammatoires et anti-oxydantes, le safran, épice dérivée de la fleur de Crocus sativus , est également connu pour ses effets positifs sur la dépression, potentiellement par ses propriétés ISRS-like. Cependant, les mécanismes moléculaires sous-jacents à ces effets et leurs avantages pour la santé humaine ne sont pas encore clairs. Grâce à une approche clinique ex vivo originale, nous avons démontré pour la première fois que les métabolites humains circulants produits suite à la consommation de safran (Safr'Inside TM) protègent les neurones humains de la neurotoxicité induite par le stress oxydatif en préservant la viabilité cellulaire et en augmentant la production de BNDF. En particulier, les métabolites ont significativement stimulé la libération de dopamine et de sérotonine. De plus, les métabolites du safran étaient également capables de protéger le tonus sérotoninergique en inhibant l'expression du transporteur de sérotonine SERT et en régulant à la baisse le métabolisme de la sérotonine. Au total, ces données apportent de nouvelles connaissances biochimiques sur les mécanismes sous-jacents à l'impact bénéfique du safran sur la viabilité et l'activité neuronale chez l'homme, dans le contexte du stress oxydatif lié à la dépression.

National audience; Our society nowadays is aging and the chronic disease appearance is increasing. Toprevent this, plant-derived nutrients like polyphenols could be used. They are known toprotect tissues from inflammatory and metabolic dysregulation induced by chronic diseases.Polyphenols are found in high level in artichoke leaf extract (ALE) and his ingestion may beeffective to prevent such dysregulations. To prove this, an innovative clinical approach wasdesigned. Patients ingested ALE and their blood was collected every 20 min after theingestion during 240 min. The kinetic profile of the ALE absorption was studied by1H NMRspectroscopy. The comparison of 1D spectra showed that the highest variations wereobserved in the phenolic compounds’ region and for the 100 min samples. The addition ofthe degradation products of chlorogenic acid, the major ALE polyphenol compound, to anaive serum led to similar chemical shift variations to those observed for the 100 minsamples suggesting that the metabolic changes in the serum profile after ingestion were dueto the presence of the ALE polyphenol metabolites. These results, then, allowed to continuethe clinical trial and to determine the influence of sera enriched in metabolites resultingfrom ALE consumption on the behavior of human hepatocyte, adipocyte and chondrocytecultures. Altogether, the obtained data show that polyphenols from artichoke may representa relevant alternative for nutritional strategies addressing chronic disease issue [1].References:1. Wauquier F.; Boutin-Wittrant L.; Viret A.; Guilhaudis L et al. Nutrients. 2021, 13 (8), 2653.DOI: https://doi.org/10.3390/nu13082653