Anti-inflammatory and anticancer effects of flavonol glycosides from Diplotaxis harra through GSK3β regulation in intestinal cells
Autor: | Raoudha Mezghani-Jarraya, Cynthia Girardi, Rachid Chawech, Nicolas Fabre, Imen Nasri, Audrey Ferrand, Emmanuel Mas, Nathalie Vergnolle, Claire Racaud-Sultan |
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Přispěvatelé: | Université de Sfax, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), CHU Toulouse, Hôpital des Enfants, Unité de Gastroentérologie, Hépatologie et Nutrition, Département de Pédiatrie, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Racaud-Sultan, Claire, Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Service Gastroentérologie, hépatologie nutrition, diabétologie et maladies héréditaires du métabolisme pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse) |
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Magnetic Resonance Spectroscopy Flavonols [SDV]Life Sciences [q-bio] Anti-Inflammatory Agents glycogène synthase kinase3 Pharmaceutical Science 0302 clinical medicine Tandem Mass Spectrometry GSK-3 Drug Discovery Glycosides Receptor Chromatography High Pressure Liquid chemistry.chemical_classification biology medicine.diagnostic_test cytotoxicité food and beverages General Medicine Glycogen synthase kinase 3b glycogen synthase kinase 3β Biochemistry 030220 oncology & carcinogenesis Colonic Neoplasms Molecular Medicine medicine.symptom Signal Transduction Research Article Cell Survival medicine.drug_class Inflammation Flowers diplotaxis Anti-inflammatory 03 medical and health sciences Western blot medicine Humans cancer Flavonoids Intestine Cancer activité anti-inflammatoire Protein Kinase Inhibitors intestine Pharmacology Glycogen Synthase Kinase 3 beta Plants Medicinal Plant Extracts Methanol lcsh:RM1-950 Glycoside Brassicaceae Inflammatory Bowel Diseases biology.organism_classification Antineoplastic Agents Phytogenic lcsh:Therapeutics. Pharmacology 030104 developmental biology Complementary and alternative medicine chemistry inflammation Cell culture Solvents cellule épithéliale intestinale flavonoïde Caco-2 Cells inflammation de l'intestin Phytotherapy |
Zdroj: | Pharmaceutical Biology Pharmaceutical Biology, Taylor & Francis, 2017, 55 (1), pp.124-131. ⟨10.1080/13880209.2016.1230877⟩ Pharmaceutical Biology 1 (55), 124-131. (2017) Pharmaceutical Biology, Vol 55, Iss 1, Pp 124-131 (2017) Pharmaceutical biology Pharmaceutical biology, 2017, 55 (1), pp.124-131. ⟨10.1080/13880209.2016.1230877⟩ |
ISSN: | 1744-5116 1388-0209 |
Popis: | International audience; Context and objective: Diplotaxis harra (Forssk.) Boiss. (Brassicaceae) is traditionally used as an antidiabetic, anti-inflammatory or anticancer agent. In these pathologies, the glycogen synthase kinase 3 b (GSK3b) is overactivated and represents an interesting therapeutic target. Several flavonoids can inhibit GSK3b and the purpose of this study was to search for the compounds in Diplotaxis harra which are able to modulate GSK3b. Materials and methods: Methanol extracts from D. harra flowers were prepared and the bio-guided fractionation of their active compounds was performed using inflammatory [protease-activated receptor 2 (PAR2)-stimulated IEC6 cells] and cancer (human Caco-2 cell line) intestinal cells. 50–100 lg/mL of fractions or compounds purified by HPLC were incubated with cells whose inhibited form of GSK3b (Pser9 GSK3b) and survival were analyzed by Western blot at 1 h and colorimetric assay at 24 h, respectively. LC-UV-MS profiles and MS-MS spectra were used for the characterization of extracts and flavonoids-enriched fractions, and the identification of pure flavonoids was achieved by MS and NMR analysis. Results: The methanol extract from D. harra flowers and its flavonoid-enriched fraction inhibit GSK3b in PAR2-stimulated IEC6 cells. GSK3b inhibition by the flavonoid-enriched D. harra fraction was dependent on PKC activation. The flavonoid-enriched D. harra fraction and its purified compound isorhamnetin-3,7- di-O-glucoside induced a 20% decrease of PAR2-stimulated IEC6 and Caco-2 cell survival. Importantly, normal cells (non-stimulated IEC6 cells) were spared by these treatments. Conclusion: This work indicates that flavonoids from D. harra display cytotoxic activity against inflammatory and cancer intestinal cells which could depend on GSK3b inhibition. |
Databáze: | OpenAIRE |
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