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
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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