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Lexa Robin.Annette.SMZ886.Pdf AVERTISSEMENT Ce document est le fruit d'un long travail approuvé par le jury de soutenance et mis à disposition de l'ensemble de la communauté universitaire élargie. Il est soumis à la propriété intellectuelle de l'auteur. Ceci implique une obligation de citation et de référencement lors de l’utilisation de ce document. D'autre part, toute contrefaçon, plagiat, reproduction illicite encourt une poursuite pénale. Contact : [email protected] LIENS Code de la Propriété Intellectuelle. articles L 122. 4 Code de la Propriété Intellectuelle. articles L 335.2- L 335.10 http://www.cfcopies.com/V2/leg/leg_droi.php http://www.culture.gouv.fr/culture/infos-pratiques/droits/protection.htm Université de ffieÈe Centredes sciencesde I'environnenlent Thèse de Doctorat de I'Université de Metz mentionSciences présentéeet soutenuepubliquement le 24 Octobre l98A parAnnette LEXA-ROBIH t / _ Plopriétéscholérétiques, antihépatotoxiques et diurétiques d'Eupatorlum cannabinum L.: approcheethnôpharmacologique BIBLIOTHEOIJEUNIVERSITAIRE DE METZ Membresdu jury: M. J.M.Pelt, professeur (président du jury) |ilil ililililril lllil rilllil illlill llllllillll M. J. Atkinson,professeur (rapporteur) o22 420288 2 entin, maîtrede conférences(directeur de thèse) M. Larrey,docteur M. F. Mortier,professeur (rapporteur) M. G. Mazarjl docteur M. B. Capolaghi.docteur Maitre, de qui avez-vous appris le Tao? demanda Man Po à Mu Yu. De Itécriture de Ia lecture de I'éveil de I'attention du travail du son de I'inconnu du vide de I'infini sans commencement lui répondit-if. Tchouang Tseur 3èIne siècte avant J.C. À ur le profesesur if.li. Pelt, merci. EIBI.IOTHËQUT UN I VhRS IIA,IRI s/& wle À itacqusa Fleurentin, maitre de conférences à Ituniversité de Metz, Ie guide de ces travaux. Je n,ai cessé de louer sa disponibilité et son humeur égale en toutes circonstances À Ur le profess€ur François llortl.er, professeur de pharmacognosie à Ia faculté de pharmacie de Nancy, la juste mesure entre compétence et sens de lthumour. mercL. A Unê ll.e. Fuzell,er, naitre de conférences à la faculté de phamacie de Nancy, pour ntavoir fait gentinent et gracieusement bénéficier de ses compétences et de son sérieux, A llr P.Irebr, maitre de recherche au C.N.R.S., pour l'aide et les conseils pratiques gui mta apportés, A ClaLre Eoeffler, l,tarLe-Claire L,anbers, Donlnique Beaux, I.licbel itoyeua, Eassan Eaôi et Pierre-Yves lnrLs, pour la pierre que chacun a apportée à cet rfédif icerr, À Àlaln Rolland, Ie coeur sur Ia main, une mention toute spéciale, À Frédérl.o 9ol.c, pour aâ contrlbution informatique, avec toute mon anitié, A it€an-Clauû€ Block, Paule Vasaeur, itean-FrançoLs Fenard, l{arcelle Grunfelder aLnsl que tout le personnel et tous mes collègues passés et présents ôu Centre des Sciences de I 'Environnenent, Pour tous leurs conseils , leur gentillesse, Pour tout ce çlue j'ai appris grâce à eux et qui ne se résume pas à une thèse, merci. A I{r Ie professeur Atkinson, professeur de pharnracotogie à la faculté des Sciences Pharmaceutiques de Nancy, A ur uazars, docteur , directeur du centre dthistoire de la médecine à ltuniversité Louis Pasteur de Strasbourg, pour sa contribution ayurvédiquê, A ur capolaghi, docteur en sciences pharmaceutiques et biologiste à I'hôpital Bel-Àir de Thionville, gui mta accueillie dans son laboratoire pour me permettre d'effectuer divers dosages, A lltr Irarreyt docteur, chargé de recherche I.N.S.E.R.ll., pour avoir bien voulu accepter de juger cette thèse, rnerci, À ErLa Poitevin, A ldLchel LepetitdidLer, à qui Je dois Ia contribution graphique à cet ouvrage. Recevez ici Ie témoignage de mon anritié fidèle et de mon adniration, j'ai toujours cru en vous, aujourd'hui je sais pourquoi. merci. A Etl.enne Robin, docteur en médecine, praticien hospitalier, néphrologue et endocrinologue, A ur Carrrnane docteur en médecine, praticien hospitalier, chef de service de médecine interne et de néphrologie au C.H.R. de Thionville, A ltarc RobLn, docteur en Sciences Pharmaceutiques, pharmacologue, pour avoir airnablement accepté de me conseiller. La rencontre du milieu nédical et celui de Ia recherche est riche d'enseignements, mercl. â toue leg petits rongêurs gui ont été sacrifiés pour ce travail, mille excuses.... f, cbrl.àtopbe, j'ai puisé dans I'exemplaire oeuvre humanitaire çlue tu as accomplie loin d'ici, lâ force de mener ce travail à terme, Cette ascèse mta permis de découvrir gu'il existe sinon une raison de vivre et d'espérer, du moins une raison de trmieux- êtrerr. merci. A na rère, qui mta donné la plus belle Ieçon dt amour, de sagesse et de Joie de vivre. A non pàre, I'esprit cartésien de la famille, je Ie remercie de m'avoir donné Ie gott de l'étude, De m'avoir permis de mener à bien mes années universitaires, Et d'avoir bien voulu mettre ses compétences orthographiques au senrice de la rédaction scientifigue. A na fanLlle, merci. I i -:\'..\ I AOI.|UAIRE PAGES INTRODUETTON 1àre PARIIE 3 ErUDE BTBLTOGRAPEIOITE À BTUDE BOTANTQUB À'.1 ETUDE DU GENRE EUPATORII,II| L. 4.1.1 IÀ FAII{ILI,E DES ASTERÀCEAE À. t-.1.1 TAXONOMTE A. r.. 1.2 DESCRIPTTONBOTANTQUE 4.1_.2 POSITTON SYSTEI{ATIQUE DU GENREEUPATORII,II{ L. I DÀNS IÀ FÀTIIILLE DES ASTERÀCEÀE 4.1.2.1 IÀ TRIBU DES EUPATORIEAE 4.L.2.2 IÀ TRTBU DES EUPATORIINEAE A. ]..2.3 I,E GENREEUPATORIT'I{ L. L1 A. 1. 2.3.L POSTTIONSYSTEMATTQUE 4.1.2.3.2 CLE DE DETERMTNATIONDU GENREEUPATORII'I{ L. 4.2 ETUDE DE L,ESPECE E.cannabinum L. L4 4.2.1 CLE DE DETERITIINATIONDE L'ESPECE E.cannabinum L. L4 4.2.2 DTSTRIBUTION GEOGRÀPHIQUE 20 4.2.3 NOMSVERNACUTÀIRES 20 B T'TILI8ÀTION TRADITTONNEI,IJE 20 C CEII,IIE 25 C.1 TERPENOIDES 25 c. 1.1 IÀCTONES SESQUTTERPENTQUES C.1.2 TRITERPENESET STEROIDES C.1.3 DITERPENES C.1.4 II{ONOTERPENES C. 1.5 HUILE ESSENTIELLE C.2 FIÀVONOIDES 33 C.3 DERIVES AIIIINES 35 C.3 1 ÀLCAI-,OIDES c.3 .2 AI{INO-ALCOOLS C.4 ÀCIDES-PHENOT,S 36 C.5 ACIDES-ALCOOLS 37 C.6 DERIVE DE BENZOFT'RANNE 37 C.7 DERIVES DE BENZOPYRANNE 38 C.8 SUCRES 38 D PEâruACOÎroGIB DE CERTAIITES STRUCTURES CtrII.IIQUBS PREAENTE8 DÀltg 1,8 cEl{RB Bupatorlun L. 39 D.l PTIARI{ACOI,OGIE DES FIÂVONOTDES 39 D. 2 PHARITIÀCOI,OGIE DES ÀCIDES-PHENOT,S 4L D. 3 PHARMACOLOGIE DES ALCAIOIDES PYRROLIZIDTNIQUES 42 B CEIUTE ET PEARITACOIOGIE DE DIFFERENTES ESPECEE 43 DL GENRE EupatorLum L. 8.1 IÀCTONES SESQUTTERPENTQUES 43 8.2 FIÀVONOIDES 46 8.3 ALCAI,OIDES 46 8.4 HUILE ESSENTIELLE 50 8.5 POLYSACCHARIDES 50 F ETITDE PAARUACOIJoGIQUE DrE.cannabinum Ir. 5l_ ,ène pARTTE pREpARÀTroN BT cÀRAcrERrgATroN 53 DEg EXTRAfT8 DeE.cannabl.num L. A COIIPES nISTOLOGIQUES 54 B PREPARÀTION DB L'ENTRÀIÎ ÀQUEUX D,E.c!]nnab:Lr|gg I,. 56 B. 1 PROTOCOI,ED'EXÎRÀCTTON 8.2 IPTS UTILISES C CARACTERISATION DE I,,EXTRAIT 59 C.1 }I,ATERIEL ET METHODES C.l 1 PREPÀRÀTTONDES EXTRÀTTS C.L.2 IDENTIFICATION DES EXTRÀITS EN C.C.M. C.2 RESULTATS ET DISCUSSTON c.2. L IÂCTONES SESQUITERPENIQUES C.2.2. FI,AVONOTDESET ACTDES-PHENOLS c.2.3 ACTDES-ALCOOLS C.2.4 ALCAIôIDES e.2.5 TENEUREN IONS Na+ etK+ D CONCLUSTON 68 tène peRTrE BTUDEptrARuAcoroorgun DE r.'ExrRÀrr AQI'EIIX D,Egcannab:Lnlrm L. CONDITIONS D'EI..EVAGE ET D'EXPERTUENTATION DE8 ANTUAUX 69 A BÎUDB DE LÀ TOXICITE AIGUB DE L'EXTRAIT AQITEUX 7L Dr&Sgnnab:l1qgg L. CIIBZ LA 8OURIS 4.1 I.{ATERTELET METHODES A.2 RESULTATS ET DTSCUSSTON B PROPRIETE8 CEOLERBTIQUE8D'E.cannabLnun Ir. 74 8.1 ANALYSE BTBLTOGRAPET9UE 8.1.I- LE FLUX ACTDES BILIAIRES DEPENDANT 8.1.2 LE FLUX ACIDES BILIAIRES INDEPENDANT 8.1.3 LE FLUX EXTRÀHEPATOCYTAIRE 8.2 INFIJUEITCEDE IJ,EXTRAIT ÀQUEUXD,E.e|annablnlrn I.,. 80 SUR LE FIJUX BIIJIâIRE CHEU IE RÀT 8.2.1 MATERIEL ET METHODES 8.2.2 STATTSTTQUES 8.2.3 RESULTATS 8.2.4 ANALYSE DES RESULTATS 8.3 RECBERCBEDU SITE D'ACTION D'E.cannab:LEg4 L. 8UR LA FORIIATION DE LÀ BILE 8.3.1 INFLUBNCB DE L'EXTRAIT AQUEUXD'E.cannabitlu[ L. 90 gUR IrB TAUX D'ÀCIDBB BIIrIÀfRES DAltg L'l BIL,E 8.3.1.1 MATERIEL ET METHODES 8.3.1.2 STATTSTTQUES 8.3.1.3 RESULTATS 8.3.1.4 ANALYSEDES RESULTÀTS 8.3.2 TIÛPLUENCEDE rrrBxrRârr AeuBUx DrE.cannabLnun L. 95 gUR LA CI,ATRAIICE BIIJIATRB A IJ'ERTTHRITOIJ 8.3.2.1 MÀTERIEL ET I{ETHODES 8.3.2.2 EXPRESSIONDES RESULTATSET STATTSTIQUES 8.3.2.3 RESULTATS 8.3.3.4 ÀNALYSEDES RESULTATS B.l. DISCUSSION 106 B. 4 . 1 ANALYSE COMPARÀTIVE B. 4. 2 REIÀTION STRUCTURE/ACTMTE e PROPRIETE8 INTfBEPATOTOXIQUES D'E.cannabinum Ir. c.1 rltFrruEllcE DE rrrExrRArr D'E.eannabinum rJ. vrg-À-vrs 1i-6 DE Ir'EEPATTTE rNDItrrE PÀR r,E cclt rlf vrvo cEE,z LB RAr c. 1. t_ ANÀLYSE BIBLTOGRÀPHTQUE c.t.1.1 METABOLISMEDU CC14 c.1_.1.2 TilÎOXICATION EXPERTMENTÀLEAU CCt4 IN VM c. t . L.2.L ADMNISTRÀTIONDU TOXTQUE c. L. L.2.2 ANALYSESBIOCHIMTQUES c. 1. 1. 3 LES ÀNTTHEPÀTOIOXIQUES C.1.1.3.1 LES MOLECULESDE SYNTHESE C. 1. 1. 3.2 II{OLECULESD'ORIGTNE NÀTURELLE C.L.2 INTLÛENCE D'UN PRETRATTEUENTET D'UN ].30 PC'8T-TRÀITEUENT DTEXTRârT ÀguEux DrE.cannablput[ L. Vrg-A-VIg DE I,'INIOXICÀTION EXPERTUENTALBÀU CClt CHEZ LE RAT C.1.2.1 I,TÀTERTELET METHODES c.L.2.2 STÀTISTIQUES C.I..2.3 RESULTÀTS C.1.2.4 ANALYSEDES RESULTATS C.2 UTSE AU POT!ÛITD'T'ITE ÎBCENIQUE D,EVAIJUÀTrON DE L4L IJ'EFFET INTINEPAIIOTOXTQUE D,E.CANNAbI.NUM IJ.
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