ANTHRAQUINONE (ANTHRACENE) GLYCOSIDES

ANTHRAQUINONE (ANTHRACENE) GLYCOSIDES • Anthraquinonederivativesaretheactivecomponentsinanumberofcrudedrugswithpurgative(cathartic)properties.

• Distributedinvariousfamilies•  Theiraglyconeisanthracenetype• Manyofthemareusedtechnicallyasdyessinceanthraquinonesarecolouredsubstances.

• Catharticdrugs---RhizomaRhei,Aloe,FoliaSennae• Drugsusedasdyes----Coccionella,RadixRubiae

1 Doç.Dr.SinemAslanErdem

ANTHRAQUINONES

•  Theyarefoundinplantsas1.  Oxanthrone2.  Anthrone3.  Anthraquinoneformsanddimers

ofthesestructures• ANTHRAQUINONEisthemoststableform.

2 Anthracene Doç.Dr.SinemAslanErdem

ANTHRAQUINONES

•  1,8-dihydroxyanthraquinonederivativesaretheonesexhibitpurgativeactivityandimportantinpharmacy

• DimerizationàDianthrone/dianthranolfromC10positionwithC-Cbond.

• O-GlycosideàGlycosylationwith–OHin1,6,8,9,10.C(e.g.)• C-GlycosideàGlycosylationfrom10.Cposition,C-Cbond

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Emodin-L-rhamnosideFranguloside

Aloin

Doç.Dr.SinemAslanErdem

ANTHRAQUINONES •  R1(C3)R2(C6)•  -CH2OH-H(ALOE-EMODIN)•  -CH3-H(CRYSOPHANOL)•  -CH3-OH(EMODIN)•  -CH3-OCH3(PHYSCION)

•  -COOH-H(REIN)


ANTHRAQUINONES

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rein + rein HOMODIANTHRON

Ø  Thetwoanthronemoietiesaresame


ANTHRAQUINONES

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rein + emodol HETERODIANTHRON

Ø  Thetwoanthronemoietiesaredifferent

EMODIN


ANTHRAQUINONES

•  Freeanthracenederivativesà%0.2-0.8• Anthraceneglycosidesandpolimersà%1-7•  Indrieddrugs,anthranolandanthrahydroquinoneamountswilldecreaseandanthraquinoneamountwillincreaseàoxidation


ANTHRAQUINONES

IDENTIFICATION1)FreeanthracensidentifiedwithBORNTRAGERreaction;• Organicsolventextract+alkaline–OHàredcolour• Onlyanthraquinones;glycosidesafterhydrolised,anthronsandanthronolsafteroxidisationgivesBorntragerreaction


ANTHRAQUINONES

•  2)AnthranolsareidentifiedwithSCHÖNTETENreaction• Waterextract+Na-borateàgreenfluorescent•  3)Anthronesgivedifferentcolorswithp-nitrosodimethylanilinewhileanthraquinonesdoesn'tgiveanycolor.


QUANTIFICATIONØ Quantityinplantsdependson;• Collectiontime• Methodofdrying•  Storageperion•  Shelftimeofdrug

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ANTHRAQUINONES


1)COLORIMETRICASSAY:FreeanthraquinonequantificationwithBorntragerreaction(a)

• Reducedderivative:OxidationwithH2O2thenapplyBorntragerreaction(b)

•  (b-a)!result2)GRAVIMETRICASSAY3)BIOLOGICALASSAYàFühnerMethod

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ANTHRAQUINONES


Ø USAGE-EFFECTS•  1)Purgative:Increaseinlargebowel•  Freeanthraquinonesarelesssolubleinwater;lesseffective•  Glycosidesarepolarmolecules;theyaresolubleinwater.Theyareneitherresorbednorhydrolisedinsmallintestines.Hydrolisedbybeta-glycosidasefoundinfloraoflargebowelàreleasedanthraquinonesreducedtoanthronsswhicharebioactive.TheseanthronsincreasetheperistaltismofbowelandinhibitNa-KATPase;thusthisresultswithwater,natriumandchloridstayinbowelsandthissoftensthefeces.

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ANTHRAQUINONES


•  Effectivein10-15thhoursofintake•  Effectivealsoparenterally• Morephenolic–OHàmoreefficiency•  Thus;mosteffectiveanthraquinoneàEMODINE• Non-effective---------REIN• Mosteffectivederivativesdianthrones,o-glycosidesofanthroquinonesandC-glycosidesofanthrones,respectively.

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ANTHRAQUINONES


ANTHRAQUINONES Structure-Activity Relationship 1.  Situation of phenolic substituents is related with the activity: • Hydroxylation at C-1 and C-8 is essential for activity • Phenolic substituent in α-position à increase in PURGATIVE

activity • Acetylation of phenolic group à decrease in efficiency 2.  If drug contains both tannins and anthraquinones à decrease

in LAXATIVE activity •  In lower dosage ------ ASTRINGENT •  In high dosage ---- LAKSATIVE, PURGATIVE


ANTHRAQUINONES

3.  Someskinillnesses(psoriasis,dryegzema)àANTISEPTIC(e.g.Chrysarobin)

4.  VeterinaryàANTISEPTIC(e.g.Aloe)


RHIZOMA RHEI (TK), Rhubarb

Ø Rheumsp.(Polygonaceae)Ø 2sections:Ø PALMATASECTION:Ø RheumpalmatumØ Rheumofficinale


Ø RheumpalmatumØ Rheumofficinale


RHIZOMA RHEI (TK)

ü RHAPONTICASECTION:ü R.rhaponticumü R.compactumü R.undulatumü R.ribes


RHIZOMA RHEI (TK)

Ø Rheumpalmatumvar.tauguticum---NorthChinaØ R.officinale------SouthChinaØ DrugobtainedfromtheseplantsareknownasChineseRhubarbØ IndriedChineseRhubarb;Ø Totalanthracene-----%3-5Ø Tannoids(Catechol,glucogallin)----%5


RHIZOMA RHEI (TK)

Ø Freeanthraquinones%0.1-0.2;Ø Crysophanol(C3àCH3)Ø Emodin(C3àCH3;C6àOH)Ø Physcion(C3àCH3;C6àOCH3)Ø Aloe-emodin(C3àCH2OH)Ø Rein(C3àCOOH)


RHIZOMA RHEI (TK)

Ø Glycosides:MajorcompoundsØ AnthraquinoneglycosidesØ AnthranolveanthroneglycosidesØ Polymercompounds:Ø SennidineAandB-----DireinanthroneØ PalmidinA,B,C---Heterodianthrone(emodin+crysophanol)


RHIZOMA RHEI (TK)

Ø USESØ LowDosage(50-100MG)---ASTRINGENTØ HighDosage(500MG-2G)---LAXATIVE,PURGATIVEØ Notirritant;elderlyandchildrencanuse.


RHIZOMA RHEI (TK)

ü Rheumrhaponticum-----EnglishRhubarbü India;Europeàornamentalplantü Rhizomescontainlessactiveingredientsà%1-3ü FreeanthraquinonesàCrysophanol,Emodin


RHIZOMA RHEI (TK)

ü Rhaponticoside-----estrogenicglycoside

ü Usedasrhubarb;2-4timeslessefectivethanChineserhubarb


RHIZOMA RHEI (TK)

v Rheumribes(Işgın):v TheuniqueRheumspeciesfromTurkeyv EastAnatoliaàVan,Elazığv Petiolsareusedasvegetablev Anthracenederivativesvetanninsv Traditionallyusedasastringent


RHIZOMA RHEI (TK)

• Anatomicproperties:•  Starhilumintransversesectionofcambiumisspecific• Relativelylarge(50-120µ)calciumoxalateclustercrystalsalsospecificØ Thesepropertieshelptoidentifythedrugeasily


CORTEX FRANGULAE (Ph.E) Alder buckthorn, Barut Ağacı • Rhamnusfrangula(Rhamnaceae)• Driedbarksofthetrunkandbranches• GrowsinMediumandSouthEurope•  InTurkey;NorthandMediumAnatolia,Trabzon,İstanbul,Bolu,Ankara,Bursa


CORTEX FRANGULAE (Ph.E) (BARUT AĞACI) • DrugobtainedfromPoland,CzechRepublic,YugoslaviaandRussia•  Thisdrugshouldbeusedayearafteritiscollectedorafterdriedin1000Cforanhour.


CORTEX FRANGULAE (Ph.E) (BARUT AĞACI) • Outerlayerofthebarksisdarkgreycoloured,haswhiteellipsoidlenticels;innerlayerisyellow-orangecoloured

• Rowsofdrusecrystalarespecificfortheidentificationofthedrug• Anthracenederivativesà2-4%•  Freeanthraquinonesà0.05-0.1%(Crysophanol,Emodin)


CORTEX FRANGULAE (Ph.E) (BARUT AĞACI) • Asanthraceneglycodises;• Glucofranguloside----Emodin+Rh+Gl(from–OHin1.or8.Cpositions)(Primaryglycoside)

•  Franguloside-----Emodin+Rh(Scondaryglycoside)•  EmodindianthroneàDimericstructure• Heterodianthrone(emodin+crysophanol)—PALMITINC


CORTEX FRANGULAE (Ph.E) (BARUT AĞACI)

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GLUCOFRANGULOSIDE(PRIM.GLY.)

PALMITIN(HETERODIANTHRONE)

EMODINDIANTHRONE


CORTEX FRANGULAE (Ph.E) (BARUT AĞACI) •  ThedrugcanbeusedinDecoctionorLiquidextractformsorinpowderedform

• ActsasLaxative-Purgative


CORTEX RHAMNI PURSHIANAE (TF), Cascara Sagrada, Cascara Buckthorn (Ph.E.) • Rhamnuspurshiana(Rhamnaceae)• Driedbarksofyoungtrunkandbranches• Americanplant,culturedinKenya•  ThedrugisobtainedbetweenApril-Augustanddriedinshadow•  Thedrugshouldbeusedayearafteritiscollectedorafterdryinganhourin100°C


CORTEX RHAMNI PURSHIANAE (TF), CASCARA SAGRADA (Ph.E.) •  Thedrugistypicallymoreorlesscoveredwithlichens•  Thedrugconsistsofratherthickfragments(2-4mm),cutinto10-20cmstrips,greycolouredwithlenticelsontheoutersurface

• PowdereddrugconsistsofsclereidsandbasicseriesofCa-oxalatecrystals


CORTEX RHAMNI PURSHIANAE (TF), CASCARA SAGRADA (Ph.E.) •  4-5%Anthracenederivatives:•  FreeAnthraqinonesà0.2-0.8%(Crysophanol,Emodin,Aloe-emodin)


CORTEX RHAMNI PURSHIANAE (TF), CASCARA SAGRADA (Ph.E.) • O-Glycosides:•  Emodin-oxanthroneglycoside•  Emodin-anthroneglycoside

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Emodin-oxanthroneglycoside

Emodin-anthroneglycoside


CORTEX RHAMNI PURSHIANAE (TF), CASCARA SAGRADA (Ph.E.) • C-Glycosides:• Aloin(Aloe-emodinantronglycoside)• Chrysaloin(Chrysophanolanthroneglycoside)

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Aloin(Aloe-emodinantronglycoside) Chrysaloin(Chrysophanolanthroneglycoside)


CORTEX RHAMNI PURSHIANAE (TF), CASCARA SAGRADA (Ph.E.) • PrimaryGlycosides:• CascarosideA(Aloin’sprimaryglycoside)(+)• CascarosideB(Aloin’sprimaryglycoside)(-)


CORTEX RHAMNI PURSHIANAE (TF), CASCARA SAGRADA (Ph.E.) • CascarosideC(Krizaloin’sprimaryglycoside)(+)• CascarosideD(Krizaloin’sprimaryglycoside)(-)• Glycosidicbondsfrom1.and8.positions• Powder(250mg-1g)• Usedaslaxative,purgative


FRUCTUS RHAMNI CATHARTICAE Akdiken Meyvesi, Buckthorn Fruit (TK) • MaturefruitsofRhamnuscathartica(Rhamnaceae)•  Fruitsarein6-8mmdiameter,drupa,collectedinSeptember-October

• GrowsinSouthEurope,NorthAfrica,Mediterranean•  InTurkey;Abant,Trabzon


FRUCTUS RHAMNI CATHARTICAE AKDİKEN MEYVESİ (TK) • Anthraceneamountà0.7-1.4%• Anthracenesmainlyfoundinseeds,lessinpulp•  -Emodin•  -Franguloside(Emodin6-O-rhamnoside)•  -Emodin-anthranolglycoside


FRUCTUS RHAMNI CATHARTICAE AKDİKEN MEYVESİ (TK) •  FlavonoidsarefoundinPulp•  Flavonolderivatives:• KaempferolandQuercetinderivatives

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Kaempferol Quercetin


FRUCTUS RHAMNI CATHARTICAE AKDİKEN MEYVESİ (TK) • CatharticosideàMethyletherofkaempherol

•  Fruitjuice(doesn’tcontainAnthracene)----diureticduetoFlavonols•  Fruit-----actsaslaxative,purgative;usedinveterinary


Rhamnus petiolaris, Buckthorn, Boyacı Dikeni, Cehri • GrowsinTurkey;Exported•  FruitsoftheplantgrowinginKaysericonsistsof4%fixedoiland0.08-0.15%freeanthracenes


• Barks:•  -Freeanthraquinones0.12%•  Emodin,PhysicionFiskiyon,chrysophanol•  -Heterozit%0.9•  Emodol,physcion,krizofanolglycosides

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Rhamnus petiolaris, Buckthorn, Boyacı Dikeni, Cehri


•  Fruitswasonceusedaspurgative,notanymore• Containsayellowcolouringcompoundàusedasyellowdyeforfabricsandoils

• Over20RhamnusspeciesaregrowinginAnatolia;fruitsandbarksofsomeofthesespeciesareusedaspurgative

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Rhamnus petiolaris, Boyacı Dikeni, Cehri


FOLIA SENNAE (TK) Sinameki Yaprağı, Senna leaves (Ph.E.) • DriedleavesofsomeCassia(Leguminosae/Fabaceae)species• GrowsinNorthAfrica,semi-desertandmountainsofArabia• Drugisobtainedfrom:• Cassiaangustifolia(Arabia)-------FoliaSennaetinnevelly(Tinnevellysenna)

• Cassiaacutifolia(TropicalAfrica)------FoliaSennaealexandrina(Alexandriansenna)


FOLIA SENNAE (TK) SİNAMEKİ YAPRAĞI (Ph.E.) •  FoliaSennaeTinnevelly;•  Leavesareof3-5cm,yellowish-green,glabrous•  ThisdrugismarketinginTurkey•  FoliaSennaeAlexandrina;•  Leavesareof2-4cm,greyish-green,bothlayersarepubescent


FOLIA SENNAE (TK) SİNAMEKİ YAPRAĞI (Ph.E.) •  Fruitsoftheseplantsarealsousedasdrug,namedasFructusSennae•  FoliaSennae


FOLIA SENNAE (TK) SİNAMEKİ YAPRAĞI (Ph.E.) • Bothleavesandfruitscontainanthracenederivatives2-3%•  -FreeAnthraquinones:• Rein(0.05-0.10%)• Chrysophanol,Emedin•  -Glycosides:FoundinLeaves;•  SennosideAandB---acidhydrolysis---SennidinAandB(Direinanthrone)+2molGl.


FOLIA SENNAE (TK) SİNAMEKİ YAPRAĞI (Ph.E.) •  SennidinA------d•  SennidinB-------opticallyinactive

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SennosideAandB(Direinanthrone


FOLIA SENNAE (TK) SİNAMEKİ YAPRAĞI (Ph.E.) •  SennosideCandD---acidhydr.---SennidinCandD(Heterodianthrone----aloe-emodin+rein)+Gl+Gl

52 SennosideCandD(hetrodianthroneàaloe-emodin+rein)


FOLIA SENNAE (TK) SİNAMEKİ YAPRAĞI (Ph.E.) •  Fruits;•  SennosideAandB• GlucosennosideAandB(Primaryglycoside)

•  Leavesalsocontainsakindofirritantresin•  Leavescanbegetridofthisresinbywashedwith95°Ethanol(resinwillberemovedat¼ratio)


FOLIA SENNAE (TK) SİNAMEKİ YAPRAĞI (Ph.E.) • Resin----irritanttouterusvebladder•  Fruitsmustbeusedafterremovaloftheirritantseeds• Drugisusedaslaxativeandpurgativeinformsofpowder,infusionorenema


FOLIA SENNAE (TK) SİNAMEKİ YAPRAĞI (Ph.E.) ENEMA:•  F.Sennae------15g• Na2SO4--------15g• Water--------------500gINFUSION:•  5-10gsennaleaves+200mlboiledwateràwaitfor5’àfilteranddrink


FOLIA SENNAE (TK) SİNAMEKİ YAPRAĞI (Ph.E.) •  SennosideAandB(10-40mg)----UsedasLaksative-Purgative• Cassiaalata,C.aphylla,C.fistulaveC.nigricansspeciesalsocanbeusedforthesamepurposes;especiallyC.fistulaisusedforchildrenasamild,pain-freepurgativeinformof5%infusion


FOLIA SENNAE (TK) SİNAMEKİ YAPRAĞI (Ph.E.)

PREPARATIONS• ROHA-LAX--------SennosideA(tablet,granule)•  SENOKOT--------SennosideB•  TİLAX-----F.Sennae+Fr.Coriandri+Fr.Anisi•  +R.Liquiritiae• X-M-DİETSOLÜSYON---SennosideA+BCalcium(150mg)• Purgative------SennosideA+Bkalsiyum(300mg)


FOLIA SENNAE (TK) SİNAMEKİ YAPRAĞI (Ph.E.) • X-M-SOLÜSYON-----SennosideA+Bkalsiyum• BEKUNİS----Sennoside• AGİOLAX(Granül)----PlantagoovataseedsPlantagoovataseedcoatSinamekifruit• KARBOSEPTİN(Tablet)-----CarboLigniSoufredepuratumSennayaprağıRh.RheiextractFenolftalein


FRUCTUS CASSIAE FISTULAE

• MaturefruitsofCassiafistula•  Indiaandtropicalregions• Pulpofthefruitisusedasdrug


FRUCTUS CASSIAE FISTULAE

• Pulp;• Pectin,musilageandsugarsà50%•  1-3%àAnthracenederivatives• AmongfreeanthracenesREINisthemostabundant•  SENNOSIDEAandB•  Laxativein5-10gdoses


ALOE (TF) SARISABIR

• Aloeisajuice,obtainedfromleavesofvariousAloe(Liliaceae)species.

• Aloeferox(A.lucida)-----SouthAfrica• Dentateleaves,flowersarered• Aloevera(A.Barbadense=A.vulgaris)---NorthAfrica• Dentateleaves,flowersareyellow


ALOE (TF) SARISABIR

v Aloeferox-Aloelucida(CapeAloes):v Thejuiceisconcentratedbyboiling.Greenish-yellowcolouredØ Aloevera-Aloehepatica(CuracaoAloes/BarbadaAloes):Ø Thejuiceiscself-oncentrated;darkcoloured,opaque


ALOE (TF) SARISABIR

• Anthrasenosides15-30%• ALOIN(=Barbaloin)(BarbadaAloesà15-30%),(CapeAloesà15-20%)


ALOE (TF) SARISABIR

• ALOIN(Aloe-emodinC-glycoside)----oxidanthydrolysisbyNaperiodateorFeCl3àAloe-emodin+Gl.

•  FreeAnthraquinones0.05-0.5%• Aloe-emodin


ALOE (TF) SARISABIR

• Resin10-20%(Anthracenepolymer)

• Resinisirritantforuterus.Notusedinpregnantsandhemorrhoidpatients

• Purgativeàactsonlargebowel• Piluleform100mgdoses----laxative200-500mgdoses---purgative


ARAROBA, Goa Powder, Goa Tozu

• Andiraararoba(Fabaceae)• AtreefromBrasilianforests•  Yellowpowderfoundinschizolysigenoussecretorypockets• Anthrone,AnthranolandrelatedcompoundsàChrysarobin• DrugàEvaporatedhotbenzeneextractofpowder


ARAROBA, Goa Powder, Goa Tozu

• Antisepticandantiparasitic.• Usage;skindisordersespeciallypsoriasis


RADIX RUBIAE, BOYACI KÖKÜ

• Rubiatinctorium(Rubiaceae)commonmadder,dyer’smadder• Driedundergroundparts•  SouthwestEurope• Adyeobtainedfromtheroots---knownas”EdirneKırmızısı”or“TürkKırmızısı”



• ColouringcompoundsàAnthraquinoneswhichcontain-OHgroupsin1stand2ndpositions

•  Thesecompounds:• Alizarin----1,2dihydroxyanthraquinone



• Purpurin---1,2,4trihydroxyanthraquinone



• Ruberythricacid---alizaringlycoside(alizarin+Gl+xyl)

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RuberythricacidDoç.Dr.SinemAslanErdem

COCCIONELLA, Cochineal

• Driedfemaleinsect,Coccuscacti(Coccidae)•  TheyareespeciallyfoundonacactusnamedOpuntiacoccinelifera(Cactaceae);inMexicoandPeruregions

•  Insectsarebrushedfromplants;insectsarekilledbywatervapor,ethervapororsulphurfumes;driedundersunlightorinovenat400C


COCCIONELLA

•  Insectscontain10%carminicacid

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Carminicacid


HERBA HYPERICI, St. John’s Wort, Sarı Kantaron •  FloweredbranchesofHypericumperforatum(Hypericaceae)taze• AEuropeanplant• WidelydistributedinTurkey•  Leavesarecoatedwithmanyglandularhairs;whentheleavesareheldinthelightoildropletsareseenasbrightspots.


HERBA HYPERICI, SARI KANTARON

•  -DIANTHRONstructuredcompounds:• Hypericines• Hypericine----hexahydroxydimethylnaftadianthrone•  İsohypericine• Pseudohypericine• Protohypericine



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Hypericine(emodindianthrone)

Isohypericine(emodindianthrone)



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Protohypericine(emodindianthrone)

Pseudohypericine(emodindianthrone)



• Hypericineisnotpurgative• Usedinfatigueandmentaldepressionastonicandstimulant.•  ItisaPhotosensitivecompound



St. John’s wort oil (Kantaron yağı)•  Floweredbranchesareallowedtostandinoliveoilfor15days;filteredandused.

•  Traditionallyusedinwoundhealing•  EssentialoilofH.perforatum----antihelmentic



•  Thereareabout70HypericumspeciesgrowinginTurkeyØ Speciesusedtraditionally:• H.calycinum• H.empetrifolium• H.tetrapterum• H.triquetrifolium• H.scabrum(Yozgat)• H.heterophyllum(Ankara)



• GermanComissionArecommendsforanxiety,depressivemoods,skininflammations,woundandburns

•  Standardizedextractofthedrugisusedin300mgdosesfordepression3timesinaday.


ANTHRAQUINONE (ANTHRACENE) GLYCOSIDES

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