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ET Hyoscyamus Albus L REPUBLIQUE ALGERIENNE DEMOCRATIQUE ET POPULAIRE MINISTERE DE L’ENSEIGNEMENT SUPERIEUR ET DE LA RECHERCHE SCIENTIFIQUE UNIVERSITE HADJ LAKHDAR BATNA DEPARTEMENT DES SCIENCES DE LA NATURE ET DE LA VIE THESE pour l'obtention du diplôme de DOCTORAT TROISIEME CYCLE Filière : Sciences Biologiques Option : Biotechnologie des Molécules Bioactives et Pathologies Moléculaires Présentée par : Mlle. BENHOUDA Afaf Thème ETUDE DES ACTIVITES PHARMACOBIOLOGIQUES DES EXTRAITS d’Umbilicus rupestris (Salisb Dandy) ET Hyoscyamus albus L. Devant le jury Président : Mr. LAROUI Salah Professeur Université Hadj Lakhdar Batna Rapporteur : Mr. YAHIA Mouloud Professeur Université Hadj Lakhdar Batna Examinateur : Mr. DJEBLI Noureddine Professeur Université Ibn-Badis Mostganem Examinateur: Mr. ZELLAGUI Ammar Professeur Université Larbi-Ben Mhidi Oum Elbouagui Examinatrice: Mme. HAMBABA Leila Professeur Université Hdj Lakhdar Batna Année universitaire : 2015-2016 Remerciements Je remercie tout d’abord ALLAH tout puissant de m’avoir donné la patience, la santé et la volonté pour réaliser cette thèse. Je tiens particulièrement à remercier mon directeur de thèse, Monsieur YAHIA Mouloud, Professeur à l’Université de Batna et Directeur de notre laboratoire de recherche de m’avoir encadré, dirigé et soutenue au cours de la réalisation de cette thèse. Je remercie vivement : Le professeur LAROUI Salah, Professeur à l’Université de Batna, d’avoir bien voulu accepter de présider ce jury en dépit de leurs nombreuses occupations. Monsieur DJEBLI Noureddine, Professeur à l’Université de Mostaganem, Monsieur ZELLAGUI Ammar, Professeur à l’Université de Oum-Elbouagui, et Professeur HAMBABA Leila de l’Université de Batna pour l’intérêt qu’ils ont porté à ce travail et pour le grand honneur qu’ils me font en acceptant de le juger. Je présente mes remerciements au Dr HACHANI Khadraoui, Médecin spécialiste en anapathologie au CHU de Batna, par sa contribution par la lecture des lames. J’aimerais également exprimer ma gratitude à Mme BENBIA Souheyla, pour leur précieuse aide, et de m’avoir fait profiter de sa compétence. Merci pour tous ceux et celles qui m’ont aidé d’une façon ou d’une autre dans mon travail : Hamada HABA, Laura DE MARTINO, Luceia SOUZA, Emilia MANCINI, Sihem BOUTAGHRINE, ASMA MEDDOUR, Messaoud HACHEMI, Abdelmoudjib GHECHAM, Souad KHEBRI. Je remercie tendrement ma famille et mes proches amies qui m’ont toujours soutenue et encouragé même dans les périodes les plus difficiles, merci pour votre soutient inépuisable. Dédicaces A mes parents ; Abdelmadjid et Saliha, Pour vos mains qui ont tant travaillées, Pour votre cœur qui m’a tant donné Pour votre sourire qui m’a tant réchauffé, Pour vos yeux qui furent parfois mouillés, Pour vous qui m’avez tant aimé. Et ma fleur de mon cœur : ma sœur Djahida A mes sœurs : Soumia, Amel, Amina, Kaouthar et Isra A mon seul frère: Abderrahmane. BENHOUDA Afaf Liste des abréviations AAR : Activité antiradicalaire HAMeOH: Extrait méthanolique ALAT : Alanine amino transférase d’Hyoscyamus albus ALAT : Alanine aminotransférase Hb : Hemoglobine AlCl3 : Aluminium Chloride HbA1C: hemoglobine glyqué HCt: Hematocrite ALP: Phosphatase alcaline HGB : Hemoblobine IL-1b : Interleukine -1b AMPc : Adénosine monophosphate cyclique IL-6: Interleukine -6 AINS : Anti-inflammatoire non stéroïdien LDH : Lactate deshydrogénase ASAT : Aspartate aminotransférase MDA: Malonylaldéhyde MNU : N-méthyl- N-nitroso-urée ATPase : Adénosine triphosphatase OECD: Organisation de la coopération BBC : Blanchissement de β-carotène économique de développement Bil : Bilirubine totale PAL : Phosphatase alcaline CCM : Chromatographie sur couches PG: prostaglandine minces CH3OH : Méthanol PGE 2 : Prostaglandine E2 CHCl3 : Chloroforme PGF2-α : Prostaglandine F2-alpha CMI: Concentration minimale d’inhibition COX2: Cycoloxygénase 2. PLT : Plaquettes DMSO: Diméthylsulfoxyde RMN : Raisonance magnétique nucléaire DPPH: Diphenyl picryl- hydrazyle TG: Triglycerides EChl : Extrait chloroformique UGD : Ulcère gastroduodénal EEp : Extrait étheropétrolique URMeOH: Extrait méthanolique EMe : Extrait méthanolique. d’Umbilicus rupestris FeCl3 : Chlorure de fer STZ: Streptozotocine FNS : Formule Numérique Sanguine. TNF-α : Facteur de nécrose tumorale GB : Globule blancs VGM: Volume globulaire moyen CCMH:Volume corpusculaire moyenne en GR : Globules rouges hémoglobine STZ : Streptozotocine GMPc : Guanosine monophosphate cyclique. GPx: Glutathione peroxydase GSH: Glutathione H2SO4: Acide sulfurique AACC: American Association for Clinical Chemistry ANOVA: Analysis of Variance PAs: Pyrolizidine alkaloids DMEM: Dulbecco’s Modified Eagle’s PBS: Phosphate-buffered saline Medium SD: Standard Deviation HPLC: High-performance liquid UA: Ulcer area chromatography Liste des matières Liste des abréviations Liste des figures Liste des tableaux Introduction Partie théorique CHAPITRE I : Donnés générales sur les plantes étudiées I.1. La plante Hyoscyamus albus ......................................................................................... 1 I. 1.1. Historique de la jusquiame ............................................................................................ 1 I.1.2. Présentation de la famille des solanacées ..................................................................... 1 I.1.3. Présentation du genre Hyoscyamus ............................................................................... 1 I.1.4. L’espèce Hyoscyamus albus ...................................................................................... 2 I.2. La plante Umbilicus rupestris ................................................................................................. 7 I.2.1. Présentation de la famille des Crassulacées .................................................................... 7 I.2.2. Classifiaction botanique des d’Umbilicus rupestris ........................................................ 7 I.2.3. Proprétés thérapeutiques d’Umbilicus rupestris ............................................................. 7 CHAPITRE II : Métabolites secondaires II. 1. Polyphenols ......................................................................................................................... 9 II.1.1. Composés phénoliques ................................................................................................... 9 II.1.1.1. Tanins ..................................................................................................................... 10 II.1.1.2. Flavonoides .............................................................................................................. 10 II.1.1.3. Lignanes et lignines .................................................................................................. 21 II.1.1.4. Coumarines ............................................................................................................... 22 II.1.1.5. Stilbènes ................................................................................................................... 22 II.2. Terpenoides ........................................................................................................................... 22 II.3. Saponines .............................................................................................................................. 23 II.4. Alcaloides .............................................................................................................................. 24 Partie éxpérimentale CHAPITRE I : Matériel et Méthodes I.1. Etude phytochimique ............................................................................................................. 27 I.1.1. Matériel végétale ............................................................................................................ 27 I.1.2. Préparation des extraits .................................................................................................. 27 I.1.3. Analyse des extraits d’H.albus et U.rupestris ................................................................ 29 I.1.3.1.Analyse qualitative des extraits d’H.albus et U.rupestris .................................. 29 I.1.3.2. Analyse quantitative des extraits d’H.albus et U.rupestris .............................. 30 I.1.4. Etude des produits isolés des extraits méthanoliques des H.albus et U.rupestris ........... 31 I.2. Etude des activités pharmacobiologiques in vitro ................................................................. 33 I.2.1. Etude de l’activité cytotoxique ................................................................................... 34 I.2.2. Etude de l’activité antimicrobienne ............................................................................. 34 I.2.3. Etude de l’activité antioxydante .................................................................................. 36 I.3. Etude des activités paharmacobiologiques in vivo ................................................................ 37 I.3.1. Test de toxicité ............................................................................................................. 37 I.3.2. Etude de l’activité analgésique .................................................................................... 39 I.3.3. Etude de l’activité antipyrétque ................................................................................... 40 I.3.4. Evaluation de l’activité antinflammatoire ................................................................... 41 I.3.5. Etude de l’activité antidiabétique ...............................................................................
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