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1. 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

2. Procyanidins and hydroxytyrosol mixture exhibits anti-osteoarthritic effects: from in vitro to in vivo evidences in a rabbit post-traumatic oa model

Author

Yohann Wittrant, Nelly Urban, Laurent Beck, M. Masson, Olivier Gauthier, Tristan Richard, Christophe Merceron, Jérôme Abadie, Julie Lesoeur, V. Hivernaud, Elsa Mevel, Claire Vinatier, Stéphanie Krisa, Jérôme Guicheux, UFR Odontologie, Université Paris Diderot - Paris 7 (UPD7), Institut National de la Santé et de la Recherche Médicale (INSERM), Union Grap'Sud, Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Université de Bordeaux (UB), Institut des Sciences de la Vigne et du Vin (ISVV), Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Centre hospitalier universitaire de Nantes (CHU Nantes), Osteoarthritis Research Society International (OARSI)., and École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)

Subjects
030203 arthritis & rheumatology, 0303 health sciences, [SDV]Life Sciences [q-bio], Biomedical Engineering, Rabbit (nuclear engineering), In vitro, 3. Good health, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, chemistry, Biochemistry, Rheumatology, In vivo, Hydroxytyrosol, Orthopedics and Sports Medicine, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract

International audience

Published
2016

3. Olive and grape seed extract prevents post-traumatic osteoarthritis damages and exhibits in vitro anti IL-1β activities before and after oral consumption

Author

Jérôme Guicheux, Yohann Wittrant, Jérôme Abadie, Vincent Hivernaud, G. Nourissat, Stéphanie Krisa, Martial Masson, Laurent Beck, Christophe Merceron, Nelly Urban, Xavier Houard, Olivier Gauthier, Tristan Richard, Claire Vinatier, Julie Lesoeur, Elsa Mével, Laboratoire d'ingénierie osteo-articulaire et dentaire (LIOAD), Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Union Grap'Sud, Groupe d'Etude des Substances Végétales à Activité Biologique (GESVAB - EA 3675), Université Bordeaux Segalen - Bordeaux 2, Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Animaux modèles pour la recherche en oncologie comparée (AMaROC), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, UMR791, Laboratoire d’Ingénierie Ostéo-Articulaire et Dentaire, OTONN PHU4 CHU de Nantes, Institut National de la Santé et de la Recherche Médicale (INSERM), Animaux Mode' les pour la Recherche en Oncologie (AMaROC), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), and HAL UPMC, Gestionnaire

Subjects
Male, 0301 basic medicine, Interleukin-1beta, prévention des maladies, Administration, Oral, Nitric Oxide Synthase Type II, Pharmacology, Catechin, Mass Spectrometry, chemistry.chemical_compound, 0302 clinical medicine, Oral administration, arthrose, Medicine, Anterior Cruciate Ligament, Multidisciplinary, Phenylethyl Alcohol, surgical procedures, operative, Proanthocyanidin, Grape seed extract, Alimentation et Nutrition, Metabolome, Female, Rabbits, [SDV.SP.MED] Life Sciences [q-bio]/Pharmaceutical sciences/Medication, food.ingredient, Nitric Oxide, Dinoprostone, Article, Nitric oxide, effet de l'âge, polyphénol, 03 medical and health sciences, food, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Olea, Matrix Metalloproteinase 13, Osteoarthritis, Animals, Biflavonoids, Food and Nutrition, Proanthocyanidins, RNA, Messenger, cardiovascular diseases, 030203 arthritis & rheumatology, Grape Seed Extract, business.industry, In vitro, Diet, Bioavailability, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, chemistry, Cyclooxygenase 2, Wounds and Injuries, Hydroxytyrosol, business, rôle protecteur
Abstract

The authors are grateful to B. Fellah, I. Leborgne, and P. Roy (CRIP-ONIRIS) who contributed to experiments using rabbits; S. Sourice (Inserm UMRS 791) for her advice with histological analysis; E. Hay (Inserm UMRS 1132) for his advice with NITEGE IHC; P.Pilet for his fruitful discussion for IHC intensity analysis; F. Berenbaum for his help in DMM mice model; UTE Platform (SFR Francois Bonamy, FED 4203/ Inserm UMS 016/CNRS 3556) who provided daily care to animals and specially P. Monmousseau who provided help with forced-fed rabbits; MS and NMR experiments were undertaken at the Metabolome Facility at the Functional Genomic Center in Bordeaux, France and specially E. Renouf for her assistance in UPLC-MS analysis. R Pace who provided help with manuscript. This study was supported by Grap'Sud, Region Languedoc Roussillon, the BPI and the ANRT; International audience; Polyphenols exert a large range of beneficial effects in the prevention of age-related diseases. We sought to determine whether an extract of olive and grape seed standardized according to hydroxytyrosol (HT) and procyanidins (PCy) content, exerts preventive anti-osteoathritic effects. To this aim, we evaluated whether the HT/PCy mix could (i) have in vitro anti-inflammatory and chondroprotective actions, (ii) exert anti-osteoarthritis effects in two post-traumatic animal models and (iii) retain its bioactivity after oral administration. Anti-inflammatory and chondroprotective actions of HT/PCy were tested on primary cultured rabbit chondrocytes stimulated by interleukin-1 beta (IL-1β). The results showed that HT/PCy exerts anti-inflammatory and chondroprotective actions in vitro. The preventive effect of HT/PCy association was assessed in two animal models of post-traumatic OA in mice and rabbits. Diet supplementation with HT/PCy significantly decreased the severity of post-traumatic osteoarthritis in two complementary mice and rabbit models. The bioavailability and bioactivity was evaluated following gavage with HT/PCy in rabbits. Regular metabolites from HT/PCy extract were found in sera from rabbits following oral intake. Finally, sera from rabbits force-fed with HT/PCy conserved anti-IL-1β effect, suggesting the bioactivity of this extract. To conclude, HT/PCy extract may be of clinical significance for the preventive treatment of osteoarthritis.

Published
2016

4. Nutraceuticals in joint health: animal models as instrumental tools

Author

Yohann Wittrant, Elsa Mevel, Laurent-Emmanuel Monfoulet, Christophe Merceron, Laurent Beck, Véronique Coxam, Jérôme Guicheux, Université de Nantes - UFR Odontologie, Université de Nantes (UN), Service d'Odontologie Restauratrice et Chirurgicale [CHU Nantes] (PHU4 - OTONN), Centre hospitalier universitaire de Nantes (CHU Nantes), Groupe Skeletal Tissue Engineering and Physiopathology (Groupe STEP - Inserm U791 - LIOAD), Laboratoire d'ingénierie osteo-articulaire et dentaire (LIOAD), Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Union Grap’Sud [Cruviers-Lascours, France], Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Arthritis Foundation 'Courtin', National Network 'ROAD', Université de Nantes - UFR Odontologie (UFR Odonto), Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Jehan, Frederic, and Clermont Université-Université d'Auvergne - Clermont-Ferrand I (UdA)-Institut National de la Recherche Agronomique (INRA)

Subjects
Pharmacology, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, business.industry, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Nanotechnology, 3. Good health, Joint disease, Nutraceutical, Risk analysis (engineering), [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Dietary Supplements, Models, Animal, Osteoarthritis, Drug Discovery, Animals, Medicine, Joints, business
Abstract

International audience; Osteoarthritis (OA) is a degenerative joint disease with no curative treatments. Many studies have begun to demonstrate the efficacy of nutraceuticals for slowing down OA. Animal models are utilized as a compulsory step in demonstrating the protective potential of these compounds on joint health. Nevertheless, there exist a wide variety of available OA models and selecting a suitable system for evaluating the effects of a specific compound remains difficult. Here, we discuss animal studies that haveinvestigated nutraceutical effects on OA. In particular, we highlight the large spectrum of animal models that are currently accepted for examining the OA-related effects of nutraceuticals, giving recommendations for their use.

Published
2014

5. Olive and grape seed extract prevents post-traumatic osteoarthritis damages and exhibits in vitro anti IL-1β activities before and after oral consumption.

Author

Mével E, Merceron C, Vinatier C, Krisa S, Richard T, Masson M, Lesoeur J, Hivernaud V, Gauthier O, Abadie J, Nourissat G, Houard X, Wittrant Y, Urban N, Beck L, and Guicheux J

Subjects
Administration, Oral, Animals, Anterior Cruciate Ligament drug effects, Anterior Cruciate Ligament surgery, Biflavonoids pharmacology, Biflavonoids therapeutic use, Catechin pharmacology, Catechin therapeutic use, Cyclooxygenase 2 metabolism, Diet, Dinoprostone metabolism, Disease Models, Animal, Female, Grape Seed Extract pharmacology, Male, Mass Spectrometry, Matrix Metalloproteinase 13 genetics, Matrix Metalloproteinase 13 metabolism, Metabolome, Mice, Inbred C57BL, Nitric Oxide metabolism, Nitric Oxide Synthase Type II metabolism, Osteoarthritis blood, Osteoarthritis etiology, Phenylethyl Alcohol analogs & derivatives, Phenylethyl Alcohol pharmacology, Phenylethyl Alcohol therapeutic use, Proanthocyanidins pharmacology, Proanthocyanidins therapeutic use, RNA, Messenger genetics, RNA, Messenger metabolism, Rabbits, Grape Seed Extract administration & dosage, Grape Seed Extract therapeutic use, Interleukin-1beta metabolism, Olea chemistry, Osteoarthritis drug therapy, Osteoarthritis prevention & control, Wounds and Injuries complications
Abstract

Polyphenols exert a large range of beneficial effects in the prevention of age-related diseases. We sought to determine whether an extract of olive and grape seed standardized according to hydroxytyrosol (HT) and procyanidins (PCy) content, exerts preventive anti-osteoathritic effects. To this aim, we evaluated whether the HT/PCy mix could (i) have in vitro anti-inflammatory and chondroprotective actions, (ii) exert anti-osteoarthritis effects in two post-traumatic animal models and (iii) retain its bioactivity after oral administration. Anti-inflammatory and chondroprotective actions of HT/PCy were tested on primary cultured rabbit chondrocytes stimulated by interleukin-1 beta (IL-1β). The results showed that HT/PCy exerts anti-inflammatory and chondroprotective actions in vitro. The preventive effect of HT/PCy association was assessed in two animal models of post-traumatic OA in mice and rabbits. Diet supplementation with HT/PCy significantly decreased the severity of post-traumatic osteoarthritis in two complementary mice and rabbit models. The bioavailability and bioactivity was evaluated following gavage with HT/PCy in rabbits. Regular metabolites from HT/PCy extract were found in sera from rabbits following oral intake. Finally, sera from rabbits force-fed with HT/PCy conserved anti-IL-1β effect, suggesting the bioactivity of this extract. To conclude, HT/PCy extract may be of clinical significance for the preventive treatment of osteoarthritis.

Published
2016
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6. Nutraceuticals in joint health: animal models as instrumental tools.

Author

Mével E, Monfoulet LE, Merceron C, Coxam V, Wittrant Y, Beck L, and Guicheux J

Subjects
Animals, Joints, Osteoarthritis drug therapy, Dietary Supplements, Models, Animal, Osteoarthritis diet therapy
Abstract

Osteoarthritis (OA) is a degenerative joint disease with no curative treatments. Many studies have begun to demonstrate the efficacy of nutraceuticals for slowing down OA. Animal models are utilized as a compulsory step in demonstrating the protective potential of these compounds on joint health. Nevertheless, there exist a wide variety of available OA models and selecting a suitable system for evaluating the effects of a specific compound remains difficult. Here, we discuss animal studies that have investigated nutraceutical effects on OA. In particular, we highlight the large spectrum of animal models that are currently accepted for examining the OA-related effects of nutraceuticals, giving recommendations for their use., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Published
2014
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