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1. Oral supplementation with fish cartilage hydrolysate in an adult population suffering from knee pain and function discomfort: results from an innovative approach combining an exploratory clinical study and an ex vivo clinical investigation

Author

Henrotin Yves, Julie Herman, Melanie Uebelhoer, Fabien Wauquier, Line Boutin-Wittrant, Anne-Françoise Donneau, Justine Monseur, Variance Mokam Fotso, Marie Duquenne, Mélanie Wagner, Elodie Bouvret, Bérénice Costes, and Yohann Wittrant

Subjects
Chondroitin sulfate, Fish cartilage hydrolysate, Joint discomfort, Pain, Clinical efficacy, Nutraceuticals, Diseases of the musculoskeletal system, RC925-935
Abstract

Abstract Background Aging is frequently associated with impairments of the musculoskeletal system and many elderly people experience joint discomfort or pain which might reduce their ability to move and consequently alter their quality of life. A beneficial effect of fish cartilage hydrolysate (FCH) on pain and joint function has recently been shown in an ACLT/pMMx osteoarthritis rat model. Methods We therefore performed an exploratory, non-comparative, multi-centric clinical trial including 33 subjects with moderate knee joint discomfort and loss of functionality to investigate the efficacy of FCH on their algo-functional status. We further determined the potential health benefit of FCH in an original clinical ex vivo study investigating the role of FCH human metabolites on primary human chondrocytes. Results FCH significantly improved knee pain and function, as assessed by the Knee injury and Osteoarthritis Outcome Score (KOOS). Moreover, FCH significantly reduced pain at rest and while walking, and patient global assessment (PGA), as assessed by the Visual Analogue Scale (VAS), and improved patients’ quality of life (SF-36). FCH metabolites decreased the synthesis of catabolic factors (MMP-13) and pro-inflammatory mediators (NO, PGE2) and limited the inhibitory effect of IL-1β on the synthesis of cartilage matrix components (GAG and collagen). Conclusions Thus, these data provide insights on the mode of action of FCH in humans and contribute to explain how FCH may relieve pain and improve joint function in subjects with knee discomfort. Although these preliminary data need to be confirmed in a randomized controlled trial, they strongly support the potential health benefit of such an active ingredient. Trial registration: The study was registered on clinicaltrials.gov with the identifier NCT04420091 (09/06/2020).

Published
2023
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2. Reduced Production of Pro-Inflammatory and Pro-Catabolic Factors by Human Serum Metabolites Derived from a Patented Saffron Extract Intake

Author

Line Pourtau, Fabien Wauquier, Line Boutin-Wittrant, David Gaudout, Benjamin Moras, Adeline Vignault, Carole Vaysse, Tristan Richard, Arnaud Courtois, Stéphanie Krisa, Véronique Roux, Nicolas Macian, Gisèle Pickering, and Yohann Wittrant

Subjects
clinical trial, inflammation, saffron extract, crocetin, safranal, joint, Pharmacy and materia medica, RS1-441
Abstract

Safe and anti-inflammatory plant-based natural products present an increasing focus in the treatment of chronic inflammatory diseases such as osteoarthritis or inflammatory bowel diseases. Among them, saffron, a spice derived from the stigma of Crocus sativus, could have anti-inflammatory properties and would be therefore a promising therapeutic agent for the treatment of such conditions. However, the anti-inflammatory molecular mechanisms of saffron in humans are still understudied and unclear. In this study, combining human serum metabolites and cell cultures, we evaluated the effect of circulating metabolites from the consumption of a patented saffron extract (Safr’InsideTM) on the chondrocytes and colon epithelial cell responses to inflammatory stress. Parametric or non-parametric Analysis of Variance with post hoc tests was performed. We demonstrated that human serum containing metabolites from saffron intake attenuated IL-1β-stimulated production of PGE2 and MMP-13 in chondrocyte cells and limited the increase in ICAM-1, MCP-1, iNOS, and MMP-3 in human epithelial cells following combined IL-1β and TNF-α inflammatory stimulation. Altogether, these data provide new findings into the mechanisms underlying the beneficial effects of saffron on chondrocytes and enterocyte cells at the cellular level and in the context of chronic inflammatory disorders.

Published
2024
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3. Circulating Human Metabolites Resulting from TOTUM-070 Absorption (a Plant-Based, Polyphenol-Rich Ingredient) Improve Lipid Metabolism in Human Hepatocytes: Lessons from an Original Ex Vivo Clinical Trial

Author

Fabien Wauquier, Line Boutin-Wittrant, Stéphanie Krisa, Josep Valls, Cedric Langhi, Yolanda F. Otero, Pascal Sirvent, Sébastien Peltier, Maxime Bargetto, Murielle Cazaubiel, Véronique Sapone, Annie Bouchard-Mercier, Véronique Roux, Nicolas Macian, Gisèle Pickering, and Yohann Wittrant

Subjects
clinical trial, ex vivo, lipid metabolism, cholesterol, hepatocytes, Nutrition. Foods and food supply, TX341-641
Abstract

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.

Published
2023
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4. Benefits of Circulating Human Metabolites from Fish Cartilage Hydrolysate on Primary Human Dermal Fibroblasts, an Ex Vivo Clinical Investigation for Skin Health Applications

Author

Fabien Wauquier, Line Boutin-Wittrant, Elodie Bouvret, Julie Le Faouder, Véronique Roux, Nicolas Macian, Gisèle Pickering, and Yohann Wittrant

Subjects
clinical trial, skin health, primary cells, human dermal fibroblasts, marine hydrolyzed collagen, chondroitin sulfate, Nutrition. Foods and food supply, TX341-641
Abstract

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.

Published
2022
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5. Circulating Human Serum Metabolites Derived from the Intake of a Saffron Extract (Safr’InsideTM) Protect Neurons from Oxidative Stress: Consideration for Depressive Disorders

Author

Fabien Wauquier, Line Boutin-Wittrant, Line Pourtau, David Gaudout, Benjamin Moras, Adeline Vignault, Camille Monchaux De Oliveira, Julien Gabaston, Carole Vaysse, Karène Bertrand, Hélène Abrous, Lucile Capuron, Nathalie Castanon, David Vauzour, Véronique Roux, Nicolas Macian, Gisèle Pickering, and Yohann Wittrant

Subjects
clinical trial, depression, serotonin, BDNF, dopamine, SERT, Nutrition. Foods and food supply, TX341-641
Abstract

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.

Published
2022
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6. Metabolic and Anti-Inflammatory Protective Properties of Human Enriched Serum Following Artichoke Leaf Extract Absorption: Results from an Innovative Ex Vivo Clinical Trial

Author

Fabien Wauquier, Line Boutin-Wittrant, Aurélien Viret, Laure Guilhaudis, Hassan Oulyadi, Asma Bourafai-Aziez, Gwladys Charpentier, Guillaume Rousselot, Emmanuel Cassin, Stéphane Descamps, Véronique Roux, Nicolas Macian, Gisèle Pickering, and Yohann Wittrant

Subjects
clinical trial, metabolic disorders, inflammation, artichoke, polyphenols, metabolites, Nutrition. Foods and food supply, TX341-641
Abstract

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.

Published
2021
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7. Metabolic and Anti-Inflammatory Protective Properties of Human Enriched Serum Following Artichoke Leaf Extract Absorption: Results from an Innovative Ex Vivo Clinical Trial

Author

Yohann Wittrant, Stéphane Descamps, Hassan Oulyadi, Gwladys Charpentier, Gisèle Pickering, Guillaume Rousselot, Line Boutin-Wittrant, Nicolas Macian, Fabien Wauquier, Aurélien Viret, Asma Bourafai-Aziez, Véronique Roux, Laure Guilhaudis, Emmanuel Cassin, Chimie Organique et Bioorganique : Réactivité et Analyse (COBRA), Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie Organique Fine (IRCOF), Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie de Clermont-Ferrand (ICCF), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), CHU Clermont-Ferrand, Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA), CIC Clermont Ferrand, Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-Centre de Pharmacologie Clinique, CHU Gabriel Montpied [Clermont-Ferrand], Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Institut National de la Sante et de la Recherche Medicale (Inserm)European CommissionUniversity of Rouen NormandyINSA Rouen Normandy, ClinicnCell SAS, Clinic'n'Cell SAS, Institut de Chimie Organique Fine (IRCOF), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Evear Extraction, ANR-18-EURE-0020,XL Chem,XLChem, Synthesizing our future(2018), and ANR-11-LABX-0029,SYNORG,Synthèse Organique : des molécules au vivant(2011)

Subjects
0301 basic medicine, Anti-Inflammatory Agents, chondrocytes, Adipose tissue, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Pharmacology, 0302 clinical medicine, Cynara scolymus, Ingestion, TX341-641, metabolites, 2. Zero hunger, education.field_of_study, Nutrition and Dietetics, food and beverages, Biological activity, clinical trial, Hep G2 Cells, 3. Good health, Cholesterol, Liver, 030220 oncology & carcinogenesis, medicine.symptom, artichoke, Adult, medicine.drug_class, adipocytes, Population, Context (language use), Inflammation, Biology, Protective Agents, Anti-inflammatory, Article, 03 medical and health sciences, Metabolic Diseases, medicine, Humans, metabolic disorders, education, Triglycerides, polyphenols, Cell Proliferation, 030109 nutrition & dietetics, Nutrition. Foods and food supply, Plant Extracts, human cells, NMR, Plant Leaves, inflammation, Hepatocytes, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Ex vivo, Food Science
Abstract

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.

Published
2021

8. Chondroprotective properties of human-enriched serum following polyphenol extract absorption: results from an exploratory clinical trial

Author

Ruth Hornedo-Ortega, Stéphanie Krisa, Nelly Urban, Nathalie Meunier, Elsa Mevel, Henri Granel, Juliette Berger, Laurent Beck, Tristan Richard, Jérôme Guicheux, Yohann Wittrant, Line Boutin-Wittrant, Stéphane Descamps, Josep Valls, Claire Vinatier, Adeline Blot, Fabien Wauquier, Wittrant, Yohann, Unité de Nutrition Humaine (UNH), Clermont Université-Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Recherche Agronomique (INRA), Regenerative Medicine and Skeleton research lab (RMeS), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Unité de Recherche Oenologie [Villenave d'Ornon], Institut des Sciences de la Vigne et du Vin (ISVV)-Université de Bordeaux (UB)-Institut National de la Recherche Agronomique (INRA), Modulation Artificielle des Genes Eucaryotes, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Union Grap'Sud, Ortho-Traumatologie, Chirurgie plastique et reconstructive, Centre hospitalier universitaire Clermont Ferrand, Université de Nantes - UFR Odontologie, Université de Nantes (UN), CRNH Auvergne, Centre Hospitalier Universitaire de Clermont-Ferrand, Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Jehan, Frederic, Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Regenerative Medicine and Skeleton (RMeS), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Unité de Recherche Oenologie [Villenave d'Ornon] (OENO), Institut National de la Recherche Agronomique (INRA)-Université de Bordeaux (UB)-Institut des Sciences de la Vigne et du Vin (ISVV), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Service d’Orthopédie Traumatologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre de Recherche en Nutrition Humaine Auvergne [CHU Clermont-Ferrand] (CRNH A), Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Clermont-Ferrand, and Université de Nantes - UFR Odontologie (UFR Odonto)

Subjects
Male, 0301 basic medicine, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Interleukin-1beta, Anti-Inflammatory Agents, Osteoarthritis, Pharmacology, chemistry.chemical_compound, osteoarthritis (OA), cell biology, Ingestion, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Nutrition and Dietetics, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Chemistry, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, NF-kappa B, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Phenylethyl Alcohol, procyanidins, Healthy Volunteers, 3. Good health, medicine.anatomical_structure, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Alimentation et Nutrition, hydroxytyrosol, Adult, [SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Article, Chondrocyte, Young Adult, 03 medical and health sciences, Chondrocytes, In vivo, medicine, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Food and Nutrition, Proanthocyanidins, micronutrients, clinical trials, 030109 nutrition & dietetics, Grape Seed Extract, Plant Extracts, Polyphenols, medicine.disease, In vitro, 030104 developmental biology, Absorption, Physicochemical, Polyphenol, Hydroxytyrosol, Ex vivo, Food Science
Abstract

Polyphenols are widely acknowledged for their health benefits, especially for the prevention of inflammatory and age-related diseases. We previously demonstrated that hydroxytyrosol (HT) and procyanidins (PCy), alone or in combination, drive preventive anti-osteoathritic effects in vivo. However, the lack of sufficient clinical evidences on the relationship between dietary phytochemicals and osteoarthritis remains. In this light, we investigated in humans the potential osteoarticular benefit of a grapeseed and olive extract (OPCO) characterized for its hydroxytyrosol (HT) and procyanidins (PCy) content. We first validated, in vitro, the anti-inflammatory and chondroprotective properties of the extract on primary cultured human articular chondrocytes stimulated by interleukin-1 beta (IL-1 &beta, ). The sparing effect involved a molecular mechanism dependent on the nuclear transcription factor-kappa B (NF-&kappa, B) pathway. To confirm the clinical relevance of such a nutritional strategy, we designed an innovative clinical approach taking into account the metabolites that are formed during the digestion process and that appear in circulation after the ingestion of the OPCO extract. Blood samples from volunteers were collected following ingestion, absorption, and metabolization of the extract and then were processed and applied on human primary chondrocyte cultures. This original ex vivo methodology confirmed at a clinical level the chondroprotective properties previously observed in vitro and in vivo.

Published
2019

9. Metabolic profiling strategy for determination of the absorption peak of artichoke leaf extract in human enriched serum

Author

Aurélien Viret, Asma BOURAFAI AZIEZ, Wauquier, Fabien F., Line Boutin-Wittrant, Glwadys Charpentier, Emmanuel Cassin, Stéphane Descamps, Véronique Roux, Nicolas Macian, Gisèle Pickering, Guillaume Rousselot, Hassan Oulyadi, Wittrant, Y., Laure Guilhaudis, Chimie Organique et Bioorganique : Réactivité et Analyse (COBRA), Institut de Chimie Organique Fine (IRCOF), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Evear Extraction, Institut de Chimie de Clermont-Ferrand (ICCF), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Unité de Nutrition Humaine (UNH), and Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA)

Subjects
[SDV]Life Sciences [q-bio], food and beverages, [CHIM]Chemical Sciences, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
Abstract

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

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