Meni
Logotip Soria NaturalŠt. izdelkov: 1 | Skupaj: 16,89  (vklj. z DDV)

Pegasti badelj – Silybum marianum Gaertn

pegasti badelj

PEGASTI BADELJ – Silybum marianum Gaertn

Pegasti badelj izvira iz južne Evrope, Male Azije in severne Afrike. Raste tudi v centralni Evropi. Prilagodil se je podnebju v Ameriki in na jugu Avstralije.  Raste v globoki zemlji, v vlažnih, z dušikom bogatih tleh na mediteranskem področju, ob vznožju zidov, ob robu poti, na neobdelanih območjih. Cveti pozno spomladi in zgodaj poleti, nabira pa se jeseni. Pri nabiranju se najprej odreže socvetja in nato pobere semena. Znan tudi pod imenom: osat svete Marije, Marijin osat, mlečni osat, pegasti osat, bodika, ostropes, bodečnica.

I. Uporabni deli

Semena. Včasih, čeprav zelo redko, listje in korenine.

II. Aktivne sestavine

  • Flavonoidi: Med njimi izstopa podskupina kromonov, katerih mešanica se imenuje silimarin (1,5 do 3%), to je mešanica različnih derivatov flavanonov (flavanolignanov), ki se nahaja izključno v povrhnjici semena. Glavne sestavine omenjene mešanice so silibin (oziroma silibinin), silikristin in silidianin. Prav tako so prisotni derivati 3-deoksi silidianina (imenovani silimonin) in silikristina, kot tudi izosilikristina, izosilibina in njegovega derivata 3-deoksi silandrina, derivata 3-deoksi silihermina, neosilihermina A in B, 2,3-dehidrosilibin in tri- tetra- in pentameri silibina (silibinomeri). Vsebuje tudi flavonoide kot so: taksifolin, kvercetin, kvercetol, dihidrokemferol, kemferol, apigenin, naringin, naringenin, eriodiktiol, krizoeriol, 5,7-dihidroksi kromon in alkohol dihidro koniferil.
  • Sluzi
  • Amini: tiramin, agmatin in histamin.
  • Lipidi in maščobna olja (20-30%), ki vsebujejo visok delež kislin: linolne (približno 60%), oleinske (pribl. 30%) in palmitinske (pribl. 9%) v svojih trigliceridih; tokoferol (0,04%).
  • Fitosteroli (0,6%), kot: holesterol, kampesterol, stigmasterol in sitosterol.
  • Organske kisline
  • Proteini (20-30%)
  • Saponozidi
  • Sledovi eteričnih olj
  • Vitamini (C, E, K) in minerali (krom, železo, magnezij, mangan, fosfor, selen in cink).
  • Grenčine
  • Drugo: smola, itd.

III. Farmakološko delovanje

  1. Notranja uporaba:
  • Ščiti jetra (silimarin). Terapevtska učinkovitost silimarina temelji na več mehanizmih delovanja: lahko spodbuja rast jetrnih celic, jih varuje pred celično smrtjo, zavira toksine in preprečuje vnetja.

a.) Spreminja strukturo zunanje celične membrane hepatocitov tako, da preprečuje vdor hepatotoksičnih snovi v celico. Silimarin kaže izrazit jetrni tropizem in deluje kot antagonist proti številnim hepatotoksičnim snovem. Obstajajo številni poskusi na laboratorijskih živalih, ki dokazujejo inhibicijo peroksidacije membran hepatocitos tem, da se znižuje zvišane stopnje AST, ALT in LDH, ki so posledica jetrne zastrupitve s tioacetamidom, lantanidi, ogljikovim tetrakloridom, galaktozaminom, alkoholom, tetraciklini, in hepatotoksičnim virusom FV3, značilnim za hladnokrvne živali. Podobno silimarin in silibin preprečujeta zastrupitev s faloidinom in a-amanitinom (načelo zastrupitve pri zastrupitvi s falotoksini zelene mušnice). Profilaktično zdravljenje je bolj učinkovito kot terapevtsko, ko že pride do poškodbe jeter. Učinkovitost je maksimalna, če se zdravljenje izvede 6 ur preden začne delovati toksin (faloidin), medtem ko je ob uporabi silimarina 30 minut po toksinu učinkovitost manjša. Če silimarin damo s še večjim zamikom, pa ni nobenega učinka.

b.) Zmanjša aktivnost Kupfferjevih celic, (zmanjša nastanek superoksidnih radikalov, dušikovega oksida in levkotrienov), in poveča proizvodnjo glutationa, ob enem pa zmanjša njegovo oksidacijo. Silimarin v jetrnih celicah poveča količino glutationa, ki je naravni znotrajcelični antioksidant bistvenega pomena za jetra, želodec in črevesje, zelo pomemben za preprečevanje mutacij DNA in RNA. Zdi se, da je antioksidantno delovanje silimarina 10-krat močnejše od vitamina E. Poveča se tudi količina encima superoksid dizmutaze. Ta encim je skupaj z encimom glutation peroksidazo ključnega pomena pri razstrupljanju in regeneraciji jetrnih celic.

c.) Spodbuja delovanje RNA polimeraze in jedrc, s čimer se povečuje ribosomska sinteza beljakovin v jetrnih celicah, tako da to spodbuja regenerativne sposobnosti parenhima jeter in proizvodnjo novih jetrnih celic. Silimarin ne stimulira rasti malignega jetrnega tkiva. Stopnja smrtnosti med bolniki s cirozo, ki jemljejo silimarin, je znatno upadla, še posebej v primerih alkoholne ciroze.

Številne klinične študije pri odraslih bolnikih s hepatitisom kažejo, da je lahko ena od specifičnih komponent silimarina koristna pri nadzorovanju kroničnega virusnega hepatitisa. Obstajajo znanstveni dokazi, ki dokazujejo izboljšanje simptomov kroničnih jetrnih bolezni, kot so: slabost, slabotnost, zmanjšan apetit, utrujenost in bolečine v trebuhu. Dokazano je tudi, da se pri bolnikih s hudim obolenjem jeter zniža umrljivost.

  • Antioksidant (flavolignani, silimarin, silibin). Antiradikalna aktivnost je posledica stabilizacijskega delovanja silimarina na biološke membrane. Številne hepatoksične snovi ustvarjajo proste radikale v gladkem ER, kar posledično sproži tvorbo novih prostih radikalov, ki povzročajo nastanek lipidnih peroksidov na področju membran. Na tej ravni silimarin in silibin delujeta tako, da ujameta proste radikale, na ravni proizvajanja reaktivnih kisikovih zvrsti (ROS), in jih nevtralizirata, s čimer ustavitakaskadno produkcijsko verigo prostih radikalov, še zlasti lipoperoksidov. Zavirajo encim lipoksigenazo, ki katalizira reakcijo za nastanek oksidiranih polinenasičenih maščob, ki so za jetra škodljive.

Dokazano antihepatoksično delovanje je verjetno povezano tudi z antioksidativnim delovanjem in lovljenjem prostih radikalov, značilnih za silimarin in njegovo delovanje na “stabilizacijo membran”, ki se je dejansko opazovalo pri celicah kvasovk, poškodovanih z nistatinom. Klinično je bilo v dvojno slepi študiji dokazano, da silimarin (3 x 40 mg na dan) bistveno znižuje umrljivost pri bolnikih s cirozo jeter zaradi alkohola.

Silimarin tudi pri visokih odmerkih ni strupen (20,0 g/kg oralno pri podganah). Pri človeku, ko se presnovi v telesu, se v glavnem izloča z žolčem (20-40% v 24 urah) in preko ledvic (3-7%) v obliki sulfatov ali glukornatov. Ne prihaja do kopičenja. Koncentracije silibina najdemo v žolču, ob jemanju terapevtskih odmerkov, ki se določajo glede na učinkovitosti zdravila. Zato je farmakokinetično obnašanje silibina v človeku v skladu s terapevtsko učinkovitostjo.

  • Holeretik in holagog, kar pomeni, da stimulira proizvodnjo žolča in njegovo izločanje iz žolčnika (flavanolignani: silimarin in silibin, eterično olje, smola). Silibin ima dokazano antiholestatično delovanje.
  • Zmerno zvišuje krvni tlak in izboljša tonus srca (tiramin).
  • Diuretik (flavonoidi).
  • Protivneten. Silimarin ima zaviralni učinek na sintezo levkotrienov z inhibicijo 5-lipoksigenaze (5-LOX).
  • Antialergen (flavanolignani).
  • Znižuje raven lipidov in holesterola (silimarin). V študijah se je izkazalo, da ima silimarin pri podganah velik hipolipemičen učinek-, saj zmanjšuje vsebnost holesterola v jetrih in zvišuje raven  holesterola HDL-C.
  • Antitumorski (silimarin, silibin). Silibin je pokazal antitumorsko delovanje v študijah in vitro na človeških rakavih celičnih linijah jajčnikov in dojk. Prav tako je pokazal sinergistično delovanje s ciplastinom in doksorubicinom.
  • Aperitiv in digestiv (flavonoidi, grenčine).
  • Hemostatičen strjevanje krvi (flavonoidi).
  • Drugo: nekateri avtorji mu pripisujejo zmožnost blagega zniževanja vročine (antipiretik), blago hipoglikemično delovanje (krom, pomemben za regulacijo ravni sladkorja v krvi), imunostimulant (poveča proizvodnjo T-celic in interferona), venotoničen.

2. Zunanja uporaba:

  • Protivneten. Silimarin ima zaviralni učinek na sintezo levkotrienov z inhibicijo 5-lipoksigenaze (5-LOX).
  • Antitumorski (silimarin, silibin). Silimarin je ob topikalni administraciji v študijah tumorjev, ki jih pri podganah povzroča UV sevanje, pokazal zaščitni učinek pred tvorbo tumorjev kot tudi zmanjšanje njihove pojavnosti, množičnosti in velikosti.

IV. Indikacije

  1. Notranja uporaba:
  • Preprečevanje in zdravljenje bolezni jeter: hepatobiliarna insuficienca, akutni in kronični hepatitis, ciroza jeter, jetrna steatoza (zamaščena jetra), diskinezija žolčnika in vodov, kronične degenerativne bolezni jeter, jetrna nekroza, itd.
  • Zaščita jeter, predpisujejo se dolgotrajna zdravljenja, dolga vsaj 40 dni. Potem, ko že pride do poškodbe jeter, je profilaktično zdravljenje preventivno  s silimarinom bolj učinkovito od terapevtskega.
  • Bolezni žolčnika in žolčevodov: diskinezija žolčnika, žolčni kamni, holelitiaza, holangitis, holestaza.
  • Alkoholizem.
  • Zastrupitev s toksini (zelena mušnica), zdravili (kot so paracetamol, fenitoin in fenotiazini), alkoholom in strupi.
  • Ljudje, ki jemljejo zdravila, ki so potencialno škodljiva za jetra (hepatotoksična zdravila).
  • Izguba apetita, hiposekretorna dispepsija, napenjanje in vetrovi.
  • Krvavitve: hematurija, epistaksa ali krvavitev iz nosu, metroragije.
  • Vrtoglavica in bruhanje na potovanjih.
  • Alergične reakcije kot so seneni nahod, koprivnica in astma.
  • Drugo: gripa, prehlad, vnetje mehurja, ledvični kamni, oligurija, glavoboli in nevralgija, izčrpanost in astenija ali utrujenost, diabetes, itd.

2. Zunanja uporaba:

  • Eritemi in staranje kože.
  • Hemoroidi, krčne žile in razjede na nogah.

V. Kontraindikacije

  • Preobčutljivost na pegasti badelj ali druge vrste iz družine nebinovk.
  • Arterijska hipertenzija.
  • Zdravljenje z antidepresivi MAOI (inhibitorji monoaminooksidaze, encima, ki v telesu uničuje strukturo aminov kot so adrenalin, noradrenalin in serotonin). Ker vsebuje tiramin, lahko sproži hipertenzivno krizo pri bolnikih po antidepresivnem zdravljenju z MAOI.
  • Hude bolezni ledvic.
  • Biliarne obstrukcije. Pegasti badelj lahko sproži žolčne kolike in poslabša obstrukcijo zaradi holeretičnega/holagogičnega učinka
  • Nosečnost. Pegasti badelj se ne sme uporabljati med nosečnostjo zaradi pomanjkanja podatkov, ki bi podprli njegovo varnost. Izvedli so študije na različnih živalskih vrstah, v katerih so uporabili nekajkrat višje doze kot pri človeku, in niso ugotovili embriotoksičnih ali teratogenih učinkov; kljub temu pa ni bilo nobenih kliničnih testiranj na ljudeh, zato je zdravljenje s pegastim badljem dovoljeno le, če ni varnejših terapevtskih alternativ.
  • Dojenje. Pegasti badelj se ne sme uporabljati med dojenjem zaradi pomanjkanja podatkov, ki bi podprali njegovo varnost. Če ne upoštevamo, da se učinkovine pegastega badlja v znatnih količinah izločajo v materino mleko, bi to lahko vplivalo na otroka. Priporočljivo je, da prenehate z dojenjem ali jemanjem pegastega badlja.

VI. Opozorila in interakcije z zdravili

Opozorila:

  • Ker vsebuje tiramin, lahko sproži hipertenzivno krizo pri bolnikih, ki se zdravijo z antidepresivi zaviralci monoaminooksidaze (MAOI).
  • Žolčni kamni. Pegasti badelj uporabljajte previdno, saj lahko zaradi holeretičnega/holagogičnega učinka povzroči nastanek žolčnih kamnov.

Interakcije z zdravili:

  • Butirofenoni. Sočasna uporaba silimarina in butirofenonov zmanjša peroksidacijo lipidov.
  • Fenotiazini. Sočasna uporaba silimarina in fenotiazinov zmanjša peroksidacijo lipidov. Johimbin. Silimarin zmanjša učinek johimbina. V primeru sočasne uporabe je treba doze johimbina prilagoditi.
  • Peroralna kontracepcijska sredstva (estrogeni). Silibinin lahko zavira bakterijski encim β-glukuronidazo, ki sodeluje pri presnovi peroralnih kontraceptivov, tako da lahko teoretično zmanjša njihovo učinkovitost.
  • Fentolamin. Silimarin zmanjša učinke fentolamina. V primeru sočasne uporabe je treba prilagoditi odmerke fentolamina.
  • Dekstrametorfan. Silibinin je zaviralec citokroma P450, kar lahko poveča plazemske koncentracije dekstrometorfana in tako ojača njegove terapevtske in stranske učinke.
  • Nifedipin. Silibinin je zaviralec citokroma P450, kar lahko poveča plazemske koncentracije nifedipina in tako ojača njegove terapevtske in stranske učinke.
  • Peroralni antikoagulanti. Silibinin je zaviralec citokroma P450 in zato lahko poviša plazemske ravni peroralnih antikoagulantov, kar lahko povzroči krvavitve.

Kot navaja nek članek, silimarin lahko poveča ali okrepi delovanje določenih zdravil:

  • Metadon.
  • Zdravila za srce: flekainid, propafenon.
  • Antibiotiki: eritromicin, rifampin.
  • Antikonvulzijska zdravila: karbamazepin.
  • Antidepresivi: šentjanževka, bupropion, paroksetin, fluoksetin, fluvoksetin, nefazodon, sertralin, in venlafaksin.
  • Antihistaminiki: astemizol, terfenadin.
  • Antimikotiki: itrakonazol, ketokonazol.
  • Snovi, ki spodbujajo peristaltiko prebavil: cisaprid.
  • Zdravila z ergot alkaloidi: ergotamin.
  • Antipsihotiki: klozapin, pimozid.
  • Pomirjevala in uspavala: zolpidem, triazolam, midazolam, lorazepam.
  • Zdravila za zniževanje lipidov (statini): fluvastatin, lovastatin, pravastatin, simvastatin in cerivastatin.
  • Zdravila po presaditvi: ciklosporin, takrolimus.
  • Zdravila proti parazitom oz. antimalariki: atovakvon.

VII. Sekundarni učinki in toksičnost

Ob uporabi priporočenih terapevtskih odmerkov ni zabeleženih nikakršnih nezaželenih učinkov. Pri večjih odmerkih, kroničnih zdravljenjih ali pri posebej občutljivih posameznikih pa lahko pride do sledečih reakcij:

  • Alergije: Sveža rastlina lahko povzroči kontaktni dermatitis.
  • Prebavne motnje. Redko pride do blagih prebavnih motenj kot je diareja.

Silimarin tudi pri večjih količinah ni toksičen (20,0 g/kg oralno pri podganah).

 

Viri

Klinične študije:

*Favari L,  Perez-Alvarez V.  Departamento de  Farmacología y Toxicología, Centro de Investigación y de Estudios avanzados del IPN, México, D.F. Comparative effects of colchicine and silymarin on CCl4- chronic liver damage in rats. Arch Med Res. 1997 Spring;28(1):11-7. PMID: 9078581 [PubMed-indexed for MEDLINE].

*Leng-Peschlow E., Madaus AG, Ostmerheimer Str. 198, D-51109

*Koln Germany (United Kingdom). Properties and Medical Use of Flavonolignans (Silymarin) from Silybum marianum. Phytotherapy Research, Vol. 10, S25-S26 (1996).
Bean P. Rogers Memorial Hospital, Oconomowac, WI, USA. The use of alternative medicine in the treatment of hepatitis C. Am Clin Lab. 2002    May;21(4):19-21.    PMID:    12087634    [PubMed-indexed    for MEDLINE].
*Reliable phytotherapy in chronic liver diseases. Therapiewochen (Germany), 1996, 46/17 (916+918-919).

*Mourelle  M,  Muriel  P,  Favari  L,  Franco  T.Pharmacology and Toxicology Department, Cinvestav-I.P.N., Mexico. Prevention of CCL4- induced   liver    cirrhosis   by    silymarin.   Fundam   Clin    Pharmacol. 1989;3(3):183-91. PMID: 2548940 [PubMed-indexed for MEDLINE].

*Lapis K, Jeney A, Divald A, Vajta G, Zalatnai A, Schaff Z. Institute of Pathology and Experimental Cancer Research, Semmelweis Medical University, Budapest, Hungary. Experimental studies  on  the  effect  of hepatoprotective compounds. Tokai J Exp Clin Med. 1986;11 Suppl:135-PMID: 3330627 [PubMed-indexed for MEDLINE].

*Feher J, Lang I, Deak G, Cornides A, Nekam K, Gergely P. Department of  Medicine, Semmelweis University, Budapest, Hungary. Free  radicals  in  tissue  damage  in  liver  diseases  and  therapeutic approach. Tokai J Exp Clin Med. 1986;11 Suppl:121-34. PMID: 3452238 [PubMed-indexed for MEDLINE].

*Flora   K,   Hahn   M,   Rosen   H,   Benner   K.   Division   of Gastroenterology, Oregon Health Sciences University, Portland 97201-3098, USA. Milk thistle (Silybum marianum) for the therapy of liver disease. Am J Gastroenterol. 1998 Feb;93(2):139-43. PMID: 9468229 [PubMed-indexed for MEDLINE].

* Salmi HA, Sarna S. Effect of silymarin on chemical, functional, and morphological alterations of the liver. A double-blind controlled study. Scand   J   Gastroenterol.   1982   Jun;17(4):517-21.   PMID:   6753109 [PubMed-indexed for MEDLINE].

*Valenzuela  A,  Lagos  C,  Schmidt  K,  Videla  LA.  Silymarin protection against hepatic lipid peroxidation induced by acute ethanol intoxication in the rat. Biochem Pharmacol. 1985 Jun 15;34(12):2209-12. PMID: 4039940 [PubMed-indexed for MEDLINE].

*Tedesco D, Domeneghini C, Sciannimanico D, Tameni M, Steidler S, Galletti S. Department of Veterinary Science and Technology for Food Safety, Faculty of Veterinary Medicine, University of Milan, Via Celoria 10, 20133, Milan, Italy. Silymarin, a possible hepatoprotector in dairy cows: biochemical and histological observations. J Vet Med A Physiol Pathol Clin Med. 2004 Mar;51(2):85-9. PMID: 15153078 [PubMed-in process].

*Schumann J, Prockl J, Kiemer AK, Vollmar AM, Bang R, Tiegs G. Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuremberg, Fahrstrasse 17, DE-91054 Erlangen, Germany. Silibinin protects mice from T  cell-dependent liver injury. J Hepatol. 2003 Sep;39(3):333-40. PMID: 12927918 [PubMed-indexed for MEDLINE].

*Ram VJ. Medicinal Chemistry Division, Central Drug Research Institute, Lucknow, India. Herbal preparations as a source of hepatoprotective agents. Drug News Perspect. 2001 Aug;14(6):353-63. PMID: 12813598 [PubMed].

*Ahmed   B,   Khan   SA,   Alam   T.   Antihepatotoxic   Research Laboratory, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi, India. Synthesis and antihepatotoxic activity of some heterocyclic compounds containing the 1,4-dioxane ring system. Pharmazie. 2003 Mar;58(3):173-6. PMID: 12685811 [PubMed-indexed for MEDLINE].

*Dvorak Z, Kosina P, Walterova D, Simanek V, Bachleda P, Ulrichova J. Institute of Medical Chemistry and Biochemistry, Faculty of Medicine, Palacky University Hnevotinska 3, 775 15 Olomouc, Czech Republic. Primary cultures of human hepatocytes as a tool in cytotoxicity studies: cell protection against model toxins by flavonolignans obtained from Silybum marianum. Toxicol Lett. 2003 Feb 3;137(3):201-12. PMID: 12523963 [PubMed-indexed for MEDLINE].

*Lang  I,  Nekam  K,  Deak  G,  Muzes  G,  Gonzales-Cabello  R, Gergely P, Csomos G, Feher J. Second Department of Medicine, Semmelweis University Medical School, Budapest, Hungary. Immunomodulatory and hepatoprotective effects of in vivo treatment with free  radical  scavengers.  Ital  J  Gastroenterol.  1990  Oct;22(5):283-7. PMID: 1983711 [PubMed-indexed for MEDLINE].

*Jacobs  BP,  Dennehy C,  Ramirez  G,  Sapp  J,  Lawrence  VA. Department of Medicine, University of California, San Francisco 94143, USA. Milk thistle for the treatment of liver disease: a systematic review and  meta-analysis.  Am  J  Med.  2002  Oct  15;113(6):506-15.  PMID: 2427501 [PubMed-indexed for MEDLINE].

*Fiebig   M,   Wagner   H.   New   antihepatotoxic   effects   of flavonolignans of a white flowering variety of Silybum. Planta Med. 1984 Aug;50(4):310-3. PMID: 6095354 [PubMed-indexed for MEDLINE].

*Fintelmann V. Medizinische Abteilung B, Krankenhaus Rissen, Hamburg, Federal Republic of Germany. Modern phytotherapy and its uses in gastrointestinal conditions. Planta Med. 1991 Oct;57(7):S48-52. PMID: 1956958 [PubMed-indexed for MEDLINE].

*Piscitelli SC, Formentini E, Burstein AH, Alfaro R, Jagannatha S, Falloon J. Department of Pharmacy, National Institutes of Health, Bethesda, Maryland 20892-1880, USA. Effect of milk thistle on the pharmacokinetics of indinavir in healthy volunteers. Pharmacotherapy. 2002    May;22(5):551-6.    PMID:    12013352    [PubMed-indexed    for MEDLINE].

*Saller R, Meier R, Brignoli R. Abteilung Naturheilkunde, University Hospital Zurich, Switzerland. The use of silymarin in the treatment of liver diseases. Drugs. 2001;61(14):2035-63. PMID: 11735632 [PubMed- indexed for MEDLINE].

*Hernandez V.  Direct AIDS Alternative Information Resources, New York, NY. Liver function and HIV-1 infection. STEP Perspect. 1995 Summer;7(2):13-5. PMID: 11362718 [PubMed-indexed for MEDLINE].

*Venkataramanan R, Ramachandran V, Komoroski BJ, Zhang S, Schiff PL, Strom SC. Department of Pharmaceutical Sciences School of Pharmacy, Pennsylvania, USA. Milk thistle, a herbal supplement, decreases the  activity of  CYP3A4  and  uridine  diphosphoglucuronosyl transferase in  human hepatocyte cultures. Drug  Metab Dispos.  2000 Nov;28(11):1270-3. PMID: 11038151 [PubMed-indexed for MEDLINE].

*Luper S. Southwest College of Naturopathic Medicine: 2140 East Broadway Rd. Tempe, AZ 85282, USA. A review of plants used in the treatment of liver disease: part 1. Altern Med Rev. 1998 Dec;3(6):410-21. PMID: 9855566 [PubMed-indexed for MEDLINE].

*Rumiantseva ZhN. The pharmacodynamics of hepatic protectors from the lady’s-thistle (Silybum marianum). Vrach Delo. 1991 May;(5):15-PMID: 1866906 [PubMed-indexed for MEDLINE].

*Hikino H, Kiso Y, Wagner H, Fiebig M. Antihepatotoxic actions of flavonolignans   from   Silybum   marianum   fruits.   Planta   Med.   1984 Jun;50(3):248-50. PMID: 6091165 [PubMed-indexed for MEDLINE].

*Schriewer H, Weinhold F. The influence of silybin from Silybum marianum (L.) Gaertn. on in vitro phosphatidyl choline biosynthesis in rat livers. Arzneimittelforschung. 1979;29(5):791-2. PMID: 582978 [PubMed- indexed for MEDLINE].Schriewer H, Kramer U, Rutkowski G, Borgis KJ. Influence of Silybin-dihemisuccinate on fatty acid synthesis in rat liver (author’s transl). Arzneimittelforschung. 1979;29(3):524-6. PMID: 39576 [PubMed-indexed for MEDLINE.

*De Martiis M, Fontana M, Assogna G, D’Ottavi R, D’Ottavi O. Milk thistle (Silybum marianum) derivatives in the therapy of chronic hepatopathies. Clin  Ter.  1980 Aug  15;94(3):283-315. PMID: 7004762 [PubMed-indexed for MEDLINE].

*Parasassi T, Martellucci A, Conti F, Messina B. Drug-membrane interactions: silymarin, silibyn and microsomal membranes. Cell Biochem Funct. 1984 Apr;2(2):85-8. PMID: 6467519 [PubMed-indexed for MEDLINE].

*Giese LA.  Complementary healthcare practices. Gastroenterol Nurs. 2001 Jan-Feb;24(1):38-40. PMID: 11847721 [PubMed-indexed for MEDLINE].

*Wu  DF,  Peng  RX,  Ye  LP,  Yu  P.  Department  of  Pharmacy, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, China. The effects of silymarin on hepatic microsomal and mitochondrial membrane fluidity in mice. Zhongguo Zhong Yao  Za Zhi. 2003 Sep;28(9):870-2. PMID: 15015386 [PubMed-in process].

*Joyeux M, Rolland A, Fleurentin J, Mortier F, Dorfman P. Centre des Sciences de l’Environnement, Universite de Metz, France. Tert-Butyl hydroperoxide-induced injury in  isolated rat  hepatocytes: a  model for studying anti-hepatotoxic crude drugs. Planta Med. 1990 Apr;56(2):171-4. PMID: 2353064 [PubMed-indexed for MEDLINE].

*Muzes G, Deak G, Lang I, Nekam K, Gergely P, Feher J. Department of  Medicine, Semmelweis University, Budapest, Hungary. Effect of the bioflavonoid silymarin on the in vitro activity and expression of    superoxide   dismutase   (SOD)   enzyme.   Acta    Physiol   Hung. 1991;78(1):3-9. PMID: 1763650 [PubMed – indexed for MEDLINE]

*Lirussi F, Okolicsanyi L. Institute of Internal Medicine, University of Padua, Italy. Cytoprotection in the nineties: experience with ursodeoxycholic acid and silymarin in chronic liver disease. Acta Physiol Hung. 1992;80(1-4):363-7. PMID: 1345202 [PubMed-indexed for MEDLINE].

*Feher J, Cornides A, Pal J, Lang I, Csomos G. 2nd Department of Medicine, Semmelweis University, Budapest, Hungary. Liver cell protection in toxic liver lesion. Acta Physiol Hung. 1989;73(2-3):285-91. PMID: 2596318 [PubMed-indexed for MEDLINE].

*Feher J, Deak G, Muzes G, Lang I, Niederland V, Nekam K, Karteszi  M.  Liver-protective  action  of  silymarin  therapy  in  chronic alcoholic liver diseases. Orv Hetil. 1989 Dec 17;130(51):2723-7. PMID: 2574842 [PubMed-indexed for MEDLINE].

*Giese LA. Milk thistle and the treatment of hepatitis. Gastroenterol Nurs. 2001 Mar-Apr;24(2):95-7. PMID: 11847735 [PubMed-indexed for MEDLINE].

*Tanasescu C, Petrea S, Baldescu R, Macarie E, Chiriloiu C, Purice S. N. Gh. Lupu Institute of Internal Medicine, Bucharest, Romania. Use of the Romanian product Silimarina in the treatment of chronic liver diseases. Med Interne. 1988 Oct-Dec;26(4):311-22. PMID: 3072661 [PubMed-indexed for MEDLINE].

*Buzzelli G, Moscarella S, Giusti A, Duchini A, Marena C, Lampertico  M.  Istituto  di  Clinica  Medica  II,  Universita  degli  Studi  di Firenze, Italy. A pilot study on the liver protective effect of silybin- phosphatidylcholine complex (IdB1016) in chronic active hepatitis. Int J Clin Pharmacol Ther Toxicol. 1993 Sep;31(9):456-60. PMID: 8225695 [PubMed-indexed for MEDLINE].

*Par A, Roth E, Rumi G Jr, Kovacs Z, Nemes J, Mozsik G. Pecsi Tudomanyegyetem, Altalanos Orvostudomanyi Kar, I. Belgyogyaszati Klinika. Oxidative stress and antioxidant defense in alcoholic liver disease and chronic hepatitis C. Orv Hetil. 2000 Jul 23;141(30):1655-9. PMID: 10962902 [PubMed-indexed for MEDLINE].

*Shimizu I. Second Department of Internal Medicine, Tokushima University   School   of   Medicine,   Tokushima,   Japan.   Antifibrogenic therapies in chronic HCV infection. Curr Drug Targets Infect Disord. 2001 Aug;1(2):227-40. PMID: 12455417 [PubMed-indexed for MEDLINE].

*Berkson BM. Integrative Medical Center of New Mexico, New Mexico State University, Las Cruces, USA. A conservative triple antioxidant approach to the treatment of hepatitis C. Combination of alpha lipoic acid (thioctic acid), silymarin, and selenium: three case histories. Med Klin (Munich). 1999 Oct 15;94 Suppl 3:84-9. PMID: 10554539 [PubMed-indexed for MEDLINE].

*Patrick L. Hepatitis C: epidemiology and review of complementary/alternative medicine treatments. Altern Med Rev. 1999 Aug;4(4):220-38. PMID: 10468647 [PubMed-indexed for MEDLINE].

*Magliulo E, Gagliardi B, Fiori GP. Results of a double blind study on the effect of silymarin in the treatment of acute viral hepatitis, carried out at two medical centres (author’s transl). Med Klin. 1978 Jul 14;73(28-29):1060-5. PMID: 353464 [PubMed-indexed for MEDLINE].

*Trinchet JC, Coste T, Levy VG, Vivet F, Duchatelle V, Legendre C,  Gotheil  C,  Beaugrand  M.  Services  d’Hepato-Gastroenterologie et d’Anatomopathologie,   Hopital   Jean   Verdier,   Bondy.   Treatment   of alcoholic hepatitis with silymarin. A double-blind comparative study in 116 patients. Gastroenterol Clin Biol. 1989;13(2):120-4. PMID: 2707520 [PubMed-indexed for MEDLINE].

* Bode JC, Schmidt U, Durr HK. Silymarin for the treatment of acute viral hepatitis? Report of a controlled trial (author’s transl). Med Klin. 1977 Mar 25;72(12):513-8. PMID: 840125 [PubMed-indexed for MEDLINE].

*Ferenci P, Dragosics B, Dittrich H, Frank H, Benda L, Lochs H, Meryn S, Base W, Schneider B. 1st Department of Gastroenterology and Hepatology, University of Vienna, Austria. Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. J Hepatol. 1989 Jul;9(1):105-13. PMID: 2671116 [PubMed-indexed for MEDLINE].

*Lieber CS. Section of Liver Disease and Nutrition, Bronx VA Medical Center and Mt. Sinai School of Medicine, (151-2), 130 West Kingsbridge Road, Bronx, NY 10468, USA. New concepts of the pathogenesis of alcoholic liver disease lead to novel treatments. Curr Gastroenterol Rep. 2004 Feb;6(1):60-5. PMID: 14720455 [PubMed- indexed for MEDLINE].

*Lieber CS, Leo MA, Cao Q, Ren C, DeCarli LM. Section of Liver Disease & Nutrition, Bronx VA Medical Center & Mount Sinai School of Medicine,   Bronx,   New   York   10468,   USA.   Silymarin   retards   the progression of alcohol-induced hepatic fibrosis in baboons. J Clin Gastroenterol. 2003 Oct;37(4):336-9. PMID: 14506392 [PubMed-indexed for MEDLINE].

*Muriel P, Moreno MG. Section of Pharmacology, Cinvestav-IPN, Mexico 07000, DF, Mexico. Effects of silymarin and vitamins E and C on liver damage induced by prolonged biliary obstruction in the rat. Basic Clin Pharmacol Toxicol. 2004 Feb;94(2):99-104. PMID: 14748853 [PubMed-indexed for MEDLINE].

*Stickel F, Seitz HK, Hahn EG, Schuppan D. Medizinische Klinik I und Poliklinik, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen. Randomized controlled trial of silymarin treatment in patients with  cirrhosis  of  the  liver.  J  Hepatol.  1989  Jul;9(1):105-13.  PMID: 2671116 [PubMed-indexed for MEDLINE].

*Lucena MI, Andrade RJ, de la Cruz JP, Rodriguez-Mendizabal M, Blanco E, Sanchez de la Cuesta F. Clinical Pharmacology Service, University Hospital, School of Medicine, Malaga, Spain. Effects of silymarin MZ-80 on oxidative stress in patients with alcoholic cirrhosis. Results of a randomized, double-blind, placebo-controlled clinical study. Int  J  Clin  Pharmacol  Ther.  2002  Jan;40(1):2-8.  PMID:  11841050 [PubMed-indexed for MEDLINE].

*Masini A, Ceccarelli D, Giovannini F, Montosi G, Garuti C, Pietrangelo A. Sezione di Patologia Generale, Dipartimento di Scienze Biomediche Universita di Modena, Italy. Iron-induced oxidant stress leads to  irreversible  mitochondrial  dysfunctions  and  fibrosis  in  the  liver  of chronic iron-dosed gerbils. The effect of silybin. J Bioenerg Biomembr.2000    Apr;32(2):175-82.    PMID:    11768750    [PubMed-indexed    for MEDLINE].

*Jia JD, Bauer M, Cho JJ, Ruehl M, Milani S, Boigk G, Riecken EO, Schuppan D. Department of Gastroenterology and Hepatology, Friedrich-Alexander University, Erlangen-Nuernberg, Erlangen, Germany. Antifibrotic effect of silymarin in rat secondary biliary fibrosis is mediated by downregulation of procollagen alpha1(I) and TIMP-1. J Hepatol. 2001 Sep;35(3):392-8. PMID: 11592601 [PubMed-indexed for MEDLINE].

*Boigk G, Stroedter L, Herbst H, Waldschmidt J, Riecken EO, Schuppan D. Department of Gastroenterology and Hepatology, Klinikum Benjamin Franklin, Free University of Berlin, Germany. Silymarin retards collagen accumulation in early and advanced biliary fibrosis secondary to complete bile duct obliteration in rats. Hepatology. 1997 Sep;26(3):643-9. PMID: 9303494 [PubMed-indexed for MEDLINE].

*Schuppan D, Hahn EG. Clinical studies with silymarin: fibrosis progression is the end point. Hepatology. 2001 Feb;33(2):483-4. PMID: 11172360 [PubMed-indexed for MEDLINE].

*Angulo P, Patel T, Jorgensen RA, Therneau TM, Lindor KD. Division   of   Gastroenterology   and   Hepatology,   Mayo   Clinic   and Foundation, Rochester, MN, USA. Silymarin in the treatment of patients with primary biliary cirrhosis with a suboptimal response to ursodeoxycholic  acid.   Hepatology.   2000   Nov;32(5):897-900.  PMID: 11050036 [PubMed-indexed for MEDLINE].

*Schuppan D, Koda M, Bauer M, Hahn EG. Medizinische Klinik I, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Germany. Fibrosis of liver, pancreas and intestine: common mechanisms and clear targets?. Acta Gastroenterol Belg. 2000 Oct-Dec;63(4):366-70. PMID: 11233519 [PubMed-indexed for MEDLINE].

*Mourelle M, Franco MT. Departamento de Farmacologia y Toxicologia, Centro de Investigacion y de Estudios Avanzados, Instituto Politecnico Nacional, Mexico D.F. Erythrocyte defects precede the onset of   CCl4-induced  liver   cirrhosis.  Protection  by   silymarin.  Life   Sci. 1991;48(11):1083-90. PMID: 1847733 [PubMed-indexed for MEDLINE].

*Muriel P, Mourelle M. Departamento de Farmacologia y Toxicologia,  Centro  de  Investigacion  y  de  Estudios  Avanzados  del Instituto Politecnico Nacional, Mexico, D.F. The role of membrane composition in ATPase activities of cirrhotic rat liver: effect of silymarin. J Appl Toxicol. 1990 Aug;10(4):281-4. PMID: 2167906 [PubMed-indexed for MEDLINE].

*Lang I, Nekam K, Gonzalez-Cabello R, Muzes G, Gergely P, Feher  J.  Second  Department  of  Medicine,  Semmelweis  University Medical School, Budapest, Hungary. Hepatoprotective and immunological effects of antioxidant drugs. Tokai J Exp Clin Med. 1990 May;15(2-3):123-PMID: 1983370 [PubMed-indexed for MEDLINE].

*Kupcova V, Turecky L, Holoman J, Ulicna O, Brixova E, Volmut J. Therapeutic effect of silymarin in patients with liver cirrhosis. Cas Lek Cesk. 1987 Nov 6;126(45):1406-9. PMID: 3427593 [PubMed-indexed for MEDLINE].

*Benda  L,  Dittrich  H,  Ferenzi  P,  Frank  H,  Wewalka  F.  The influence of therapy with silymarin on the survival rate of patients with liver  cirrhosis  (author’s  transl).  Wien  Klin  Wochenschr.  1980  Oct 10;92(19):678-83. PMID: 7008367 [PubMed-indexed for MEDLINE].

*Reutter FW, Haase W. Clinical experience with silymarin in the treatment of chronic liver disease(author’s transl). Schweiz Rundsch Med Prax. 1975 Sep 9;64(36):1145-51. PMID: 1099576 [PubMed-indexed for MEDLINE].

*Benda L, Zenz W. Silymarin in liver cirrhosis. Wien Med Wochenschr. 1973 Sep 1;123(3):512-6. PMID: 4748151 [PubMed- indexed for MEDLINE].

*Pares A, Planas R, Torres M, Caballeria J, Viver JM, Acero D, Panes J, Rigau J, Santos J, Rodes J. Hospital Clinic i Provincial, University of Barcelona, Spain. Effects of silymarin in alcoholic patients with cirrhosis of the liver: results of a controlled, double-blind, randomized and multicenter trial. J Hepatol. 1998 Apr;28(4):615-21. PMID: 9566830 [PubMed-indexed for MEDLINE].

*Stickel F, Seitz HK, Hahn EG, Schuppan D. Medizinische Klinik I und Poliklinik, Friedrich-Alexander-Universitat Erlangen-Nurnberg, Erlangen. Alcoholic liver disease–established treatment and new therapeutic approaches. Z Gastroenterol. 2003 Apr;41(4):333-42. PMID: 12695940 [PubMed-indexed for MEDLINE].

*Bunout D, Hirsch S, Petermann M, de la Maza MP, Silva G, Kelly M, Ugarte G, Iturriaga H. Instituto de la Nutricion y Tecnologia de Alimentos (INTA), Facultad de Medicina, Universidad de Chile. Controlled study of the effect of silymarin on alcoholic liver disease. Rev Med Chil. 1992   Dec;120(12):1370-5.   PMID:   1343377   [PubMed-indexed   for MEDLINE].

*Batakov EA. Pharmacology Department, General Surgery Department, Samara  State  Medical  University, Chapaevskaya ul.  89, Samara, 443099 Russia. Effect of Silybum marianum oil and legalon on lipid peroxidation and liver antioxidant systems in rats intoxicated with carbon tetrachloride. Eksp Klin Farmakol. 2001 Jul-Aug;64(4):53-5. PMID:11589112 [PubMed-indexed for MEDLINE].

*Kravchenko   LV,   Avren’eva   LI,   Tutel’ian   VA.   Effects   of bioflavonoids on the toxicity of T-toxin in rats. A biochemical study. Vopr Pitan.  2000;69(5):20-3.  PMID:  11247160  [PubMed-indexed  for MEDLINE].

*Paulova J, Dvorak M, Kolouch F, Vanova L, Janeckova L. Vyzkumny ustav pro biofaktory a veterinarni leciva, Pohori-Chotoun. Verification of the hepatoprotective and therapeutic effect of silymarin in experimental liver injury with tetrachloromethane in dogs. Vet Med (Praha). 1990 Oct;35(10):629-35. PMID: 2102576 [PubMed-indexed for MEDLINE].

*Sonnenbichler J, Scalera F, Sonnenbichler I, Weyhenmeyer R. Max Planck Institute for Biochemistry, Martinsried, Germany. Stimulatory effects of silibinin and silicristin from the milk thistle Silybum marianum on kidney cells. J Pharmacol Exp Ther. 1999 Sep;290(3):1375-83. PMID: 10454517 [PubMed-indexed for MEDLINE].

*Thamsborg SM, Jorgensen, Brummerstedt E, Bjerregard J. Department of Clinical Studies, Royal Veterinary and Agricultural University, Frederiksberg, Denmark. Putative effect of silymarin on sawfly (Arge pullata)-induced hepatotoxicosis in sheep. Vet Hum Toxicol. 1996 Apr;38(2):89-91. PMID: 8693692 [PubMed-indexed for MEDLINE].

*Porokhniak LA, Drogovoz SM, Rogozhin BA. Action of hepatoprotective agents in a tetracycline lesion of the liver. Antibiot Med Biotekhnol. 1987 Apr;32(4):282-5. PMID: 3631934 [PubMed-indexed for MEDLINE].

*Dwivedi Y, Rastogi R, Sharma SK, Garg NK, Dhawan BN. ICMR Centre   for   Advanced   Pharmacological   Research   on   Traditional Remedies, Central Drug Research Institute, Lucknow, India. Picroliv affords protection against thioacetamide-induced hepatic damage in rats. Planta Med. 1991 Feb;57(1):25-8. PMID: 2062953 [PubMed-indexed for MEDLINE].

*Mereish KA, Bunner DL, Ragland DR, Creasia DA. Medical Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21702-5011. Protection against microcystin-LR-induced hepatotoxicity by Silymarin: biochemistry, histopathology, and lethality. Pharm Res. 1991 Feb;8(2):273-7. PMID:1902564 [PubMed-indexed for MEDLINE].

*Muriel P, Garciapina T, Perez-Alvarez V, Mourelle M. Departamento de Farmacologia y Toxicologia, Instituto Politecnico Nacional, Mexico D.F. Silymarin protects against paracetamol-induced lipid peroxidation and liver damage. J Appl Toxicol. 1992 Dec;12(6):439-PMID: 1360480 [PubMed-indexed for MEDLINE].

*Chander R, Kapoor NK, Dhawan BN. Hepatoprotective activity of silymarin against hepatic damage in Mastomys natalensis infected with Plasmodium  berghei.  Indian  J  Med  Res.  1989  Dec;90:472-7.  PMID: 2697691 [PubMed-indexed for MEDLINE].

*Meroni PL, Barcellini W, Borghi MO, Vismara A, Ferraro G, Ciani D,  Zanussi C.  Institute of  Internal  Medicine, Infectious Diseases and Immunopathology, University of Milan, Italy. Silybin inhibition of human T- lymphocyte  activation.  Int  J  Tissue  React.  1988;10(3):177-81. PMID: 3265704 [PubMed-indexed for MEDLINE].

*Boari C, Montanari FM, Galletti GP, Rizzoli D, Baldi E, Caudarella R, Gennari P. Toxic occupational liver diseases. Therapeutic effects of silymarin. Minerva Med. 1981 Oct 20;72(40):2679-88. PMID: 7290471 [PubMed-indexed for MEDLINE].

*Sonnenbichler J, Mattersberger J, Rosen H. Stimulation of RNA synthesis in rat liver and isolated hepatocytes by silybin, an antihepatotoxic agent from Silybum marianum L. Gaertn (author’s transl). Hoppe  Seylers  Z  Physiol  Chem.  1976  Aug;357(8):1171-80.  PMID: 976944 [PubMed-indexed for MEDLINE].

*He Q, Kim J, Sharma RP. Department of Physiology and Pharmacology,  College  of   Veterinary  Medicine,  The   University  of Georgia, Athens, Georgia 30602-7389. Silymarin Protects Against Liver Damage in BALB/c Mice Exposed to Fumonisin B1 Despite Increasing Accumulation of Free Sphingoid Bases. Toxicol Sci. 2004 Apr 21 [Epub ahead of print]. PMID: 15103051 [PubMed-as supplied by publisher].

*Pari  L,  Murugavel P.  Department of  Biochemistry, Faculty of Science, Annamalai University, Annamalai Nagar, Tamil Nadu 608 002, India. Protective effect of alpha-lipoic acid against chloroquine-induced hepatotoxicity in rats. J Appl Toxicol. 2004 Jan-Feb;24(1):21-6. PMID: 14745843 [PubMed-in process].

*Rastogi R, Srivastava AK, Rastogi AK. Division of Biochemistry, Central  Drug  Research Institute, Lucknow-226 001,  India.  Long  term effect of aflatoxin B(1) on lipid peroxidation in rat liver and kidney: effect of picroliv and silymarin. Phytother Res. 2001 Jun;15(4):307-10. PMID: 11406853 [PubMed-indexed for MEDLINE].

*Tuchweber B, Trost W, Salas M, Sieck R. Prevention of praseodymium-induced hepatotoxicity by silybin. Toxicol Appl Pharmacol. 1976 Dec;38(3):559-70. PMID: 1014013 [PubMed-indexed for MEDLINE].

*Szilard S, Szentgyorgyi D, Demeter I. Tisza Chemical Works Leninvaros, Occupational Health Care Service, Hungary. Protective effect of Legalon in  workers exposed to organic solvents. Acta Med Hung. 1988;45(2):249-56. PMID: 3073356 [PubMed-indexed for MEDLINE].

*Rastogi R, Srivastava AK, Srivastava M, Rastogi AK. Division of Biochemistry, CDRI, Lucknow. Hepatocurative effect of picroliv and silymarin against aflatoxin B1 induced hepatotoxicity in rats. Planta Med.2000  Dec;66(8):709-13.    PMID:    11199126    [PubMed-indexed    for MEDLINE].

*Rastogi R, Srivastava AK, Rastogi AK. Division of Biochemistry, Central Drug Research Institute, Lucknow, India. Biochemical changes induced in liver and serum of aflatoxin B1-treated male wistar rats: preventive effect  of  picroliv.  Pharmacol Toxicol.  2001  Feb;88(2):53-8. PMID: 11169162 [PubMed-indexed for MEDLINE].

*Kang JS, Jeon YJ, Park SK, Yang KH, Kim HM. Korea Research Institute   of   Bioscience   and   Biotechnology,   Taejon,   South   Korea. Protection  against  lipopolysaccharide-induced sepsis  and  inhibition  of interleukin-1beta and prostaglandin E2 synthesis by silymarin. Biochem Pharmacol. 2004 Jan 1;67(1):175-81. PMID: 14667940 [PubMed-indexed for MEDLINE].

* Vogel  VG,  Trost  W.  Anti-phalloidine activity of  the  silymarins silybine and disilybine. Arzneimittelforschung. 1975 Mar;25(3):392-3. PMID: 1174039 [PubMed-indexed for MEDLINE].

*Desplaces A, Choppin J, Vogel G, Trost W. The effects of silymarin on experimental phalloidine poisoning. Arzneimittelforschung. 1975 Jan;25(1):89-96. PMID: 125090 [PubMed-indexed for MEDLINE].

*Vogel G, Trost W. Proceedings: Neutralization of the lethal effects of phalloidine and alpha-amanitine in animal experiments by substances from the seeds of Silybum marianum l. Gaertn. Naunyn Schmiedebergs Arch Pharmacol. 1974 Mar 22;282(0):suppl 282:R102. PMID: 4276667 [PubMed-indexed for MEDLINE].

*Wellington K, Jarvis B. Adis International Limited, Auckland, New Zealand. Silymarin: a review of its clinical properties in the management of hepatic disorders. BioDrugs. 2001;15(7):465-89. PMID: 11520257 [PubMed-indexed for MEDLINE].

*Tuchweber  B,  Sieck  R,  Trost  W.  Prevention  of  silybin  of phalloidin-induced  acute  hepatoxicity.  Toxicol  Appl  Pharmacol.  1979 Nov;51(2):265-75. PMID: 531892 [PubMed-indexed for MEDLINE].

*Schleufe P, Seidel C. Zentrum Anasthesiologie, Abteilung II (Oststadt-Krankenhaus) der Medizinischen Hochschule Hannover. Amanita poisoning during pregnancy. Anasthesiol Intensivmed Notfallmed Schmerzther. 2003 Nov;38(11):716-8. PMID: 14600862 [PubMed-indexed for MEDLINE].

*Faulstich H, Jahn W, Wieland T. Silybin inhibition of amatoxin uptake in the perfused rat liver. Arzneimittelforschung. 1980;30(3):452-4. PMID: 7387753 [PubMed-indexed for MEDLINE].

*Dehmlow C, Erhard J, de Groot H. Institut fur Physiologische Chemie, Universitatsklinikum, Essen, Germany. Inhibition of Kupffer cell functions as an explanation for the hepatoprotective properties of silibinin. Hepatology. 1996 Apr;23(4):749-54. PMID: 8666328 [PubMed-indexed for MEDLINE].

*Crocenzi FA, Mottino AD, Roma MG. Instituto de Fisiologia Experimental, CONICET –  Universidad Nacional de  Rosario, Rosario, Argentina. Regulation of synthesis and trafficking of canalicular transporters and its alteration in acquired hepatocellular cholestasis. Experimental therapeutic strategies for its prevention. Curr Med Chem. 2004 Feb;11(4):501-24. PMID: 14965230 [PubMed-in process].

*Matzkies F, Webs B. Effect of a plant extract combination preparation  on  gastrointestinal  transit  time  and  bile  acid  excretion. Fortschr Med. 1983 Jul 28;101(27-28):1304-6. PMID: 6618384 [PubMed- indexed for MEDLINE].

*Schandalik R, Gatti G, Perucca E. Surgical Department, Regional Hospital, Braunau am Inn, Austria. Pharmacokinetics of silybin in bile following administration of silipide and silymarin in cholecystectomy patients.  Arzneimittelforschung. 1992  Jul;42(7):964-8.  PMID:  1329780 [PubMed-indexed for MEDLINE].

*Skottova N, Krecman V. Institute of Medical Chemistry, Medical Faculty, Palacky University, Olomouc, Czech Republic. Silymarin as a potential hypocholesterolaemic drug. Physiol Res. 1998;47(1):1-7. PMID: 9708694 [PubMed-indexed for MEDLINE].

*Skottova N, Krecman V, Walterova D, Ulrichova J, Kosina P, Simanek V. Institute of Medical Chemistry, Medical Faculty, Palacky University, Olomouc, Czech Republic. Effect of silymarin on serum cholesterol   levels   in   rats.   Acta   Univ   Palacki   Olomuc   Fac   Med.1998;141:87-9. PMID: 9684492 [PubMed-indexed for MEDLINE].

*Krecman V, Skottova N, Walterova D, Ulrichova J, Simanek V. Institute of Medical Chemistry, Medical Faculty, Palacky University, Olomouc, Czech Republic. Silymarin inhibits the development of diet- induced hypercholesterolemia in rats. Planta Med. 1998 Mar;64(2):138- PMID: 9525106 [PubMed-indexed for MEDLINE].

*Nassuato G, Iemmolo RM, Strazzabosco M, Lirussi F, Deana R, Francesconi MA, Muraca M, Passera D, Fragasso A, Orlando R, et al. Istituto di Medicina Interna, Universita di Padova, Italy. Effect of Silibinin on biliary lipid composition. Experimental and clinical study. J Hepatol. 1991 May;12(3):290-5. PMID: 1940257 [PubMed-indexed for MEDLINE].

*Lee DG, Kim HK, Park Y, Park SC, Woo ER, Jeong HG, Hahm KS.  Research  Center  for  Proteineous  Materials,  Chosun  University, Korea. Gram-positive bacteria specific properties of silybin derived from Silybum marianum. Arch Pharm Res. 2003 Aug;26(8):597-600. PMID: 12967193 [PubMed-indexed for MEDLINE].

*Kim DH, Jin YH, Park JB, Kobashi K. College of Pharmacy, Kyunghee University, Seoul, Korea. Silymarin and its components are inhibitors of beta-glucuronidase. Biol Pharm Bull. 1994 Mar;17(3):443-5. PMID: 8019514 [PubMed-indexed for MEDLINE].

*Velussi M, Cernigoi AM, De Monte A, Dapas F, Caffau C, Zilli M. Anti-Diabetes Centre, Monfalcone Hospital, Gorizia, Italy. Long-term (12 months) treatment with an anti-oxidant drug (silymarin) is effective on hyperinsulinemia, exogenous insulin need and malondialdehyde levels in cirrhotic  diabetic  patients.  J  Hepatol.  1997  Apr;26(4):871-9.  PMID:9126802 [PubMed-indexed for MEDLINE].

*Skottova N, Kazdova L, Oliyarnyk O, Vecera R, Sobolova L, Ulrichova J. Institute of Pharmacology, Medical Faculty, Palacky University, Hnevotinska 3, 775 15 Olomouc, Czech Republic. Phenolics- rich extracts from Silybum marianum and Prunella vulgaris reduce a high- sucrose diet induced oxidative stress in hereditary hypertriglyceridemic rats. Pharmacol Res. 2004 Aug;50(2):123-30. PMID: 15177299 [PubMed- in process].

*Maghrani M, Zeggwagh NA, Lemhadri A, El Amraoui M, Michel JB, Eddouks M. UFR PNPE, BP 21, Errachidia 52000, Morocco. Study of the hypoglycaemic activity of Fraxinus excelsior and Silybum marianum in an animal model of type 1 diabetes mellitus. J Ethnopharmacol. 2004 Apr;91(2-3):309-16. PMID: 15120454 [PubMed-in process].

*Savickiene N, Dagilyte A, Lukosius A, Zitkevicius V. Kauno medicinos universiteto Farmacines chemijos ir farmakognozijos katedra, A. Mickeviciaus 9, 3000 Kaunas. Importance of biologically active components and plants in the prevention of complications of diabetes mellitus. Medicina (Kaunas). 2002;38(10):970-5. PMID: 12532704 [PubMed-indexed for MEDLINE].

*Geller  LI,  Gladkikh  LN,  Griaznova  MV.  Treatment  of  fatty hepatosis in diabetics. Probl Endokrinol (Mosk). 1993 Sep-Oct;39(5):20-2. PMID: 8108340 [PubMed-indexed for MEDLINE].

*Kelly GS. Insulin resistance: lifestyle and nutritional interventions. Altern Med Rev. 2000 Apr;5(2):109-32. PMID: 10767668 [PubMed- indexed for MEDLINE].

*Feher J, Lengyel G, Blazovics A. National Institute of Internal Medicine, 2nd Dept. of Medicine, Semmelweis University, Budapest, Hungary. Oxidative stress in the liver and biliary tract diseases. Scand J Gastroenterol Suppl. 1998;228:38-46. PMID: 9867111 [PubMed-indexed for MEDLINE].

*Feher J, Lang I, Nekam K, Gergely P, Muzes G. Second Department of Medicine, Semmelweis University Medical School, Budapest, Hungary. In vivo effect of free radical scavenger hepatoprotective agents on superoxide dismutase (SOD) activity in patients.  Tokai  J  Exp  Clin  Med.  1990  May;15(2-3):129-34.  PMID: 2130521 [PubMed-indexed for MEDLINE].

*Feher  J,  Lang  I,  Nekam  K,  Muzes  G,  Deak  G.  Second Department of Medicine, Semmelweis University Medical School, Budapest, Hungary. Effect of free radical scavengers on superoxide dismutase (SOD) enzyme in patients with alcoholic cirrhosis. Acta Med Hung. 1988;45(3-4):265-76. PMID: 3249654 [PubMed-indexed for MEDLINE].

*Muzes G, Deak G, Lang I, Nekam K, Niederland V, Feher J. Semmelweis Orvostudomanyi Egyetem, II. Belgyogyaszati Klinika, Budapest. Effect of silimarin (Legalon) therapy on the antioxidant defense mechanism and lipid peroxidation in alcoholic liver disease (double blind protocol).   Orv   Hetil.   1990   Apr   22;131(16):863-6.  PMID:   2345633 [PubMed-indexed for MEDLINE].

*Feher J, Lang I, Nekam K, Csomos G, Muzes G, Deak G. Second Department of Medicine, Semmelweis University Medical School, Budapest, Hungary. Effect of silibinin on the activity and expression of superoxide dismutase in lymphocytes from patients with chronic alcoholic liver disease. Free Radic Res Commun. 1987;3(6):373-7. PMID: 3508451 [PubMed-indexed for MEDLINE].

*Varga Z, Ujhelyi L, Kiss A, Balla J, Czompa A, Antus S. Ist Department of Medicine, Medical and Health Science Centre, Debrecen, Hungary. Effect of silybin on phorbol myristate actetate-induced protein kinase C translocation, NADPH oxidase activity and apoptosis in human neutrophils. Phytomedicine. 2004 Feb;11(2-3):206-12. PMID: 15070174 [PubMed-indexed for MEDLINE]

*Griemel A, Koch H. Peroxidase isoenzymes in silybum marianum (author’s  transl).  Planta  Med.  1977  Dec;32(4):323-30. PMID:  594206 [PubMed-indexed for MEDLINE].

*Gebhardt R. Institute of Biochemistry, Medical Faculty, University of Leipzig, Leipzig, Germany. Antioxidative, antiproliferative and biochemical effects in HepG2 cells of a homeopathic remedy and its constituent plant tinctures tested separately or in combination. Arzneimittelforschung. 2003;53(12):823-30. PMID: 14732962 [PubMed- indexed for MEDLINE].

*Soto C, Recoba R, Barron H, Alvarez C, Favari L. Departamento de  Sistemas  Biologicos,  Universidad  Autonoma  Metropolitana- Xochimilco. Calzada del Hueso 1100, Col. Villa Quietud, DF CP 04960, Mexico. Silymarin increases antioxidant enzymes in alloxan-induced diabetes in rat pancreas. Comp Biochem Physiol C Toxicol Pharmacol. 2003 Nov;136(3):205-12. PMID: 14659454 [PubMed-in process].

*Chlopcikova S, Psotova J, Miketova P, Simanek V. Institute of Medical Chemistry and Biochemistry, Faculty of Medicine, Hnevotinska 3, 775 15 Olomouc, Czech Republic. Chemoprotective effect of plant phenolics against anthracycline-induced toxicity on rat cardiomyocytes. Part   I.   Silymarin   and   its   flavonolignans.   Phytother   Res.   2004  Feb;18(2):107-10. PMID: 15022159 [PubMed-indexed for MEDLINE].

*Svagera Z, Skottova N, Vana P, Vecera R, Urbanek K, Belejova M, Kosina P, Simanek V. Institute of Medical Chemistry, Palacky University, Olomouc, Czech Republic. Plasma lipoproteins in transport of silibinin, an antioxidant flavonolignan from Silybum marianum. Phytother Res. 2003 May;17(5):524-30. PMID: 12748991 [PubMed-indexed for MEDLINE].

*Johnson VJ, Osuchowski MF, He Q, Sharma RP. Department of Physiology and Pharmacology, College of Veterinary Medicine, The University of Georgia, Athens, GA 30602-7389, USA. Physiological responses to a natural antioxidant flavonoid mixture, silymarin, in BALB/c mice: II. alterations in thymic differentiation correlate with changes in c- myc  gene  expression.  Planta  Med.  2002  Nov;68(11):961-5.  PMID: 12451483 [PubMed-indexed for MEDLINE].

*Lang I, Deak G, Muzes G, Pronai L, Feher J. Second Department of Medicine, Semmelweis University, Budapest, Hungary. Effect of the natural bioflavonoid antioxidant silymarin on superoxide dismutase (SOD) activity and expression in vitro. Biotechnol Ther. 1993;4(3-4):263-70. PMID: 8292974 [PubMed-indexed for MEDLINE].

*He Q, Osuchowski MF, Johnson VJ, Sharma RP. Department of Physiology and Pharmacology, College of Veterinary Medicine, The University of Georgia, Athens, GA 30602-7389, USA. Physiological responses to a natural antioxidant flavonoid mixture, silymarin, in BALB/c mice: I induction of transforming growth factor beta1 and c-myc in liver with marginal effects on other genes. Planta Med. 2002 Aug;68(8):676-9. PMID: 12221586 [PubMed-indexed for MEDLINE].

*Varga Z, Czompa A, Kakuk G, Antus S. First Department of Medicine, University Medical School, 4012 Debrecen, Nagyerdei krt. 98. P.O. Box 19, Hungary. Inhibition of the superoxide anion release and hydrogen peroxide formation in PMNLs by flavonolignans. Phytother Res. 2001    Nov;15(7):608-12.    PMID:    11746843    [PubMed-indexed    for MEDLINE].

*Loginov AS, Matiushin BN, Sukhareva GV, Tkachev VD. Antioxidant  activity  of  hepatotropic  preparations  in  the  treatment  of chronic diseases of the liver. Ter Arkh. 1988;60(8):74-7. PMID: 3227482 [PubMed-indexed for MEDLINE].

*Skottova  N,  SVagera  Z,  Vecera  R,  Urbanek  K,  Jegorov  A, Simanek V. Institute of Pharmacology, Medical Faculty, Palacky University, Olomouc, Czech Republic. Pharmacokinetic study of iodine- labeled silibinins in rat. Pharmacol Res. 2001 Sep;44(3):247-53. PMID: 11529693 [PubMed-indexed for MEDLINE].

*Skottova  N,  Krecman  V,  Simanek  V.  Institute  of  Medical Chemistry, Medical Faculty, Palacky University, Hnevotinska 3, 775 15 Olomouc, Czech Republic. Activities of silymarin and its flavonolignans upon low density lipoprotein oxidizability in vitro. Phytother Res. 1999 Sep;13(6):535-7. PMID: 10479770 [PubMed-indexed for MEDLINE].

*Bosisio E, Benelli C, Pirola O. Institute of Pharmacological Sciences, Faculty of Pharmacy, University of Milan, Italy. Effect of the flavanolignans of Silybum marianum L. on lipid peroxidation in rat liver microsomes and freshly isolated hepatocytes. Pharmacol Res. 1992 Feb- Mar;25(2):147-54. PMID: 1635893 [PubMed-indexed for MEDLINE].

*Valenzuela A, Aspillaga M, Vial S, Guerra R. Selectivity of silymarin on the increase of the glutathione content in different tissues of the rat. Planta Med. 1989 Oct;55(5):420-2. PMID: 2813578 [PubMed- indexed for MEDLINE].

*Koch HP, Bachner J, Loffler E. Silymarin: potent inhibitor of cyclic AMP  phosphodiesterase.  Methods  Find  Exp  Clin  Pharmacol.  1985 Aug;7(8):409-13. PMID: 3001454 [PubMed-indexed for MEDLINE].

*Psotova J, Chlopcikova S, Grambal F, Simanek V, Ulrichova J. Institute of Medical Chemistry and Biochemistry, Faculty of Medicine, Palacky University, Hnevotinska 3, 775 15 Olomouc, Czech Republic. Influence of silymarin and its flavonolignans on doxorubicin-iron induced lipid peroxidation in rat heart microsomes and mitochondria in comparison with  quercetin.  Phytother  Res.  2002  Mar;16  Suppl  1:S63-7.  PMID:11933142 [PubMed-indexed for MEDLINE].

*Johnson VJ, He Q, Osuchowski MF, Sharma RP. Department of Physiology and Pharmacology, College of Veterinary Medicine, The University of Georgia, Athens, GA 30602-7389, USA. Physiological responses of a natural antioxidant flavonoid mixture, silymarin, in BALB/c mice: III. Silymarin inhibits T-lymphocyte function at low doses but stimulates  inflammatory processes  at  high  doses.  Planta  Med.  2003 Jan;69(1):44-9. PMID: 12567278 [PubMed-indexed for MEDLINE].

*Gupta OP, Sing S, Bani S, Sharma N, Malhotra S, Gupta BD, Banerjee SK, Handa SS. Regional Research Laboratory (CSIR) Jammu Tawi,  India.  Anti-inflammatory  and  anti-arthritic  activities  of  silymarin acting   through   inhibition   of   5-lipoxygenase.   Phytomedicine.   2000 Mar;7(1):21-4. PMID: 10782486 [PubMed-indexed for MEDLINE].

*Wilasrusmee C, Kittur S, Shah G, Siddiqui J, Bruch D, Wilasrusmee S, Kittur DS. Department of Surgery SUNY Upstate Medical University, Syracuse, New York 13210, USA. Immunostimulatory effect of Silybum   Marianum   (milk   thistle)   extract.   Med   Sci   Monit.   2002 Nov;8(11):BR439-43. PMID: 12444368 [PubMed-indexed for MEDLINE].

*Wilasrusmee C, Siddiqui J, Bruch D, Wilasrusmee S, Kittur S, Kittur DS. Department of  Surgery, SUNY Upstate Medical University, Syracuse, New York 13210, USA. In vitro immunomodulatory effects of herbal products. Am Surg. 2002 Oct;68(10):860-4. PMID: 12412711 [PubMed-indexed for MEDLINE].

*Amirghofran   Z,   Azadbakht   M,   Karimi   MH.   Immunology Department, Medical School, Shiraz University of Medical Sciences, PO BOX 71345-1798, Shiraz, Iran. Evaluation of the immunomodulatory effects of five herbal plants. J Ethnopharmacol. 2000 Sep;72(1-2):167-72. PMID: 10967468 [PubMed-indexed for MEDLINE].

*Kalmar L, Kadar J, Somogyi A, Gergely P, Csomos G, Feher J. Second Department of Medicine, Semmelweis University, Budapest, Hungary. Silibinin (Legalon-70) enhances the motility of human neutrophils immobilized  by  formyl-tripeptide, calcium  ionophore,  lymphokine  and  by normal  human  serum.  Agents  Actions.  1990  Mar;29(3-4):239-46. PMID: 2111081 [PubMed-indexed for MEDLINE].

*Kittur S, Wilasrusmee S, Pedersen WA, Mattson MP, Straube- West K, Wilasrusmee C, Lubelt B, Kittur DS. Department of Neurology, SUNY Upstate Medical University, Syracuse, NY 13210, USA. Neurotrophic and neuroprotective effects of milk thistle (Silybum marianum) on neurons in culture. J Mol Neurosci. 2002 Jun;18(3):265-9. PMID: 12059045 [PubMed-indexed for MEDLINE].

*Wang MJ, Lin WW, Chen HL, Chang YH, Ou HC, Kuo JS, Hong JS, Jeng KC. Department of Education and Research, Taichung Veterans General Hospital, Taichung 40705, Taiwan. Silymarin protects dopaminergic neurons against lipopolysaccharide-induced neurotoxicity by inhibiting microglia activation. Eur J Neurosci. 2002 Dec;16(11):2103-PMID: 12473078 [PubMed-indexed for MEDLINE].

*Thelen P, Jarry H, Ringert RH, Wuttke W. Department of Urology, Georg-August-University, Gottingen, Germany. Silibinin down-regulates prostate epithelium-derived Ets transcription factor in LNCaP prostate cancer  cells.  Planta  Med.  2004  May;70(5):397-400. PMID:  15124082 [PubMed-in process].

*Thelen P, Wuttke W, Jarry H, Grzmil M, Ringert RH. Department of Urology, Institute of Human Genetics, Georg-August-University, Gottingen, Germany. Inhibition of telomerase activity and secretion of prostate specific antigen by silibinin in prostate cancer cells. J Urol. 2004 May;171(5):1934-8. PMID: 15076315 [PubMed-indexed for MEDLINE].

*Hannay  JA,  Yu  D.  The  University  of  Texas,  M.D.  Anderson Cancer Center; Houston, Texas USA. Silibinin: a thorny therapeutic for EGF-R expressing tumors?. Cancer Biol Ther. 2003 Sep-Oct;2(5):532-3. PMID: 14614321 [PubMed-indexed for MEDLINE].

*Dhanalakshmi S, Agarwal P, Glode LM, Agarwal R. Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Health Sciences Center, Denver, CO 80262, USA. Silibinin sensitizes human prostate carcinoma DU145 cells  to  cisplatin- and  carboplatin- induced growth inhibition and apoptotic death. Int J Cancer. 2003 Sep 20;106(5):699-705. PMID: 12866029 [PubMed-indexed for MEDLINE].

*Ladas EJ, Kelly KM. Division of Pediatric Oncology, Columbia University, New York, NY, USA. Milk thistle: is there a role for its use as an adjunct therapy in patients with cancer?. J Altern Complement Med. 2003 Jun;9(3):411-6. PMID: 12816629 [PubMed-indexed for MEDLINE].

*Tyagi A, Bhatia N, Condon MS, Bosland MC, Agarwal C, Agarwal R. Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. Antiproliferative and  apoptotic effects of  silibinin in  rat  prostate cancer cells. Prostate. 2002 Nov 1;53(3):211-7. PMID: 12386921 [PubMed-indexed for MEDLINE].

*Kohno H, Tanaka T, Kawabata K, Hirose Y, Sugie S, Tsuda H, Mori H. First Department of Pathology, Kanazawa Medical University, Ishikawa, Japan. Silymarin, a naturally occurring polyphenolic antioxidant flavonoid, inhibits azoxymethane-induced colon carcinogenesis in male F344 rats. Int J Cancer. 2002 Oct 10;101(5):461-8. PMID: 12216075 [PubMed-indexed for MEDLINE].

*Yanaida Y, Kohno H, Yoshida K, Hirose Y, Yamada Y, Mori H, Tanaka  T.  Department  of  Laboratory  Sciences,  School  of  Health Sciences, Faculty of Medicine, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa 920-0942, Japan. Dietary silymarin suppresses 4- nitroquinoline 1-oxide-induced tongue carcinogenesis in male F344 rats. Carcinogenesis. 2002 May;23(5):787-94. PMID: 12016151 [PubMed- indexed for MEDLINE].

*Manna SK, Mukhopadhyay A, Van NT, Aggarwal BB. Department of  Molecular  Oncology,  Cytokine  Research  Laboratory,  University  of Texas M. D. Anderson Cancer Center, Houston 77030, USA. Silymarin suppresses TNF-induced activation of NF-kappa B, c-Jun N-terminal kinase, and apoptosis. J Immunol. 1999 Dec 15;163(12):6800-9. PMID: 10586080 [PubMed-indexed for MEDLINE].

*Singh RP, Agarwal R. Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Cancer Center, 4200 East Ninth Avenue, Denver, CO 80262, USA. Prostate cancer prevention by silibinin. Curr Cancer Drug Targets. 2004 Feb;4(1):1-11. PMID: 14965263 [PubMed-in process].

*Kang  SN,  Lee  MH,  Kim  KM,  Cho  D,  Kim  TS.  College  of Pharmacy, Chonnam National University, Kwangju 500-757, Republic of Korea. Induction of human promyelocytic leukemia HL-60 cell differentiation into monocytes by silibinin: involvement of protein kinase C. Biochem Pharmacol. 2001 Jun 15;61(12):1487-95. PMID: 11377378 [PubMed-indexed for MEDLINE].

*Neese S, La Grange L, Trujillo E, Romero D. Department of Behavioral Sciences, New Mexico Highlands University, 117 Hewett Hall, Las Vegas, NM 87701, USA. The effects of ethanol and silymarin treatment during gestation on spatial working memory. BMC Complement Altern Med. 2004 Feb 12;4(1):4. PMID: 15018621 [PubMed-in process]. * Reid C, Edwards J, Wang M, Manybeads Y, Mike L, Martinez N, La Grange L, Reyes E. Department of Behavioral Sciences, New Mexico Highlands University, Las Vegas, USA. Prevention by a silymarin/phospholipid compound of ethanol-induced social learning deficits in rats. Planta Med. 1999 Jun;65(5):421-4. PMID: 10418328 [PubMed-indexed for MEDLINE].

*La Grange L, Wang M, Watkins R, Ortiz D, Sanchez ME, Konst J, Lee C, Reyes E. New Mexico Highlands University, Las Vegas 87701, USA. Protective effects of the flavonoid mixture, silymarin, on fetal rat brain   and   liver.   J   Ethnopharmacol.   1999   Apr;65(1):53-61.   PMID: 10350368 [PubMed-indexed for MEDLINE].

*Giannola C, Buogo F, Forestiere G, Scaffidi L, Ferrigno V, Scaffidi A. A two-center study on the effects of silymarin in pregnant women and adult patients with so-called minor hepatic insufficiency. Clin Ter. 1985 Jul 31;114(2):129-35. PMID: 4053531 [PubMed-indexed for MEDLINE].

*Zuber R, Modriansky M, Dvorak Z, Rohovsky P, Ulrichova J, Simanek V, Anzenbacher P. Faculty of Chemical Technology, University of Pardubice, Nam. Cs. Legii 565, 532 10 Pardubice, Czech Republic. Effect of silybin and its congeners on human liver microsomal cytochrome P450 activities. Phytother Res. 2002 Nov;16(7):632-8. PMID: 12410543 [PubMed-indexed for MEDLINE].

*Beckmann-Knopp S, Rietbrock S, Weyhenmeyer R, Bocker RH, Beckurts  KT,  Lang  W,  Hunz  M,  Fuhr  U.  Institute  for  Pharmacology, Clinical Pharmacology, University of Koln, Germany. Inhibitory effects of silibinin on cytochrome P-450 enzymes in human liver microsomes. Pharmacol Toxicol. 2000 Jun;86(6):250-6. PMID: 10895987 [PubMed- indexed for MEDLINE].

*No authors listed. Toxicity. Milk thistle and indinavir. Treatmentupdate. 2002 Sep-Oct;14(7):4-5. PMID: 12400499 [PubMed- indexed for MEDLINE].

*Rajnarayana K,  Reddy MS,  Vidyasagar J,  Krishna  DR.  Drug Metabolism and Clinical Pharmacokinetics Division, University College of Pharmceutical Sciences, Kakatiya University, Warangal, AP, India. Study on the influence of silymarin pretreatment on metabolism and disposition of   metronidazole.   Arzneimittelforschung.   2004;54(2):109-13.   PMID: 15038460 [PubMed-indexed for MEDLINE].

*Mourelle   M,   Favari   L.   Departmento   de   Farmacologia   y Toxicologia, Centro de Investigacion y de Estudios Avanzados del I.P.N., Mexico, D.F. Silymarin improves metabolism and disposition of aspirin in cirrhotic rats. Life Sci. 1988;43(3):201-7. PMID: 3398694 [PubMed- indexed for MEDLINE].

*Palasciano G,  Portincasa P,  Palmieri  V,  et  al.  The  effect  of silymarin on plasma levels of malon-dialdehyde in patients receiving long- term treatment with psychotropic drugs. Curr Ther Res. 1994;55:537-545.

*Khayyal MT, el-Ghazaly MA, Kenawy SA, Seif-el-Nasr M, Mahran LG, Kafafi YA, Okpanyi SN. Department of Pharmacology, Faculty of Pharmacy, Cairo University, Cairo, Egypt. Antiulcerogenic effect of some gastrointestinally acting plant extracts and their combination. Arzneimittelforschung. 2001;51(7):545-53. PMID: 11505785 [PubMed- indexed for MEDLINE].

*Alarcon de la Lastra AC, Martin MJ, Motilva V, Jimenez M, La Casa   C,   Lopez   A.   Departamento   de   Farmacia   y   Tecnologia Farmaceutica, Facultad  de  Farmacia, Sevilla,  Spain.  Gastroprotection induced by silymarin, the hepatoprotective principle of Silybum marianum in ischemia-reperfusion mucosal injury: role of neutrophils. Planta Med. 1995 Apr;61(2):116-9. PMID: 7753916 [PubMed-indexed for MEDLINE].

*Cruz T, Galvez J, Crespo E, Ocete MA, Zarzuelo A. Effects of silymarin on the acute stage of the trinitrobenzenesulphonic acid model of rat colitis. Planta Med. 2001 Feb;67(1):94-6. PMID: 11270735 [PubMed- indexed for MEDLINE].

*Gil’miiarov EM, Radomskaia VM, Kretova IG, Vinogradova LN, Babichev AV, Ponomareva LA, Samykina LN, Sheshunov IV, Gil’miiarov EM. Biologically active additive from milk thistle in the solution of public health problems. Vopr Pitan. 1998;(3):33-5. PMID: 9752670 [PubMed- indexed for MEDLINE].

*Rui YC. College of Pharmacy, Second Military Medical University, Shanghai, China. Advances in pharmacological studies of silymarin. Mem Inst Oswaldo Cruz. 1991;86 Suppl 2:79-85. PMID: 1842018 [PubMed- indexed for MEDLINE].

*Allain H, Schuck S, Lebreton S, Strenge-Hesse A, Braun W, Gandon JM, Brissot P. Laboratoire de Pharmacologie Experimentale et Clinique, Faculte de Medecine, Universite de Rennes I, Rennes, France. Aminotransferase levels and silymarin in de novo tacrine-treated patients with Alzheimer’s disease. Dement Geriatr Cogn Disord. 1999 May- Jun;10(3):181-5. PMID: 10325444 [PubMed-indexed for MEDLINE].

*L  Pitzel,  C  Castillo  Robles,  J  Tresguerres,  S  Taubert,  V Christoffel, W Wuttke. Effects of estradiol (E2) and some phytoestrogens (PEs) containing plant extracts on differentiated 3T3-L1 fat cells. Exp Clin Endocrinol Diabetes. DOI: 10.1055/s-2004-819223

*No authors listed. An adverse reaction to the herbal medication milk thistle (Silybum marianum). Adverse Drug Reactions Advisory Committee.  Med  J  Aust.  1999  Mar  1;170(5):218-9. PMID:  10092919 [PubMed-indexed for MEDLINE]

*Lee  DY,  Liu  Y.  Bio-Organic and  Natural  Product  Laboratory, McLean Hospital/Harvard Medical School, 115 Mill Street, Belmont, Massachusetts 02478, USA. Molecular structure and stereochemistry of silybin A, silybin B, isosilybin A, and isosilybin B, Isolated from Silybum marianum (milk thistle). J Nat Prod. 2003 Sep;66(9):1171-4. Erratum in: J Nat Prod. 2003 Dec;66(12):1632. PMID: 14510591 [PubMed-indexed for MEDLINE].

*Kim NC, Graf TN, Sparacino CM, Wani MC, Wall ME. Natural Product Laboratory, Chemistry and Life Sciences, Research Triangle Institute, 3040 Cornwallis Road, Research Triangle Park, North Carolina 27709,  USA.  Complete  isolation  and  characterization of  silybins  and isosilybins from milk thistle (Silybum marianum). Org Biomol Chem. 2003 May   21;1(10):1684-9.   Erratum   in:   Org   Biomol   Chem.   2003   Oct 7;1(19):3470. PMID: 12926355 [PubMed-indexed for MEDLINE].

*Wallace SN, Carrier DJ, Clausen E. Department of Biological and Agricultural Engineering, University of Arkansas, 203 Engineering Hall, Fayetteville,  AR  72701,  USA.  Extraction  of  nutraceuticals  from  milk thistle: part II. Extraction with organic solvents. Appl Biochem Biotechnol. 2003 Spring;105 -108:891-903. PMID: 12721426 [PubMed-indexed for MEDLINE].

*Barreto JF, Wallace SN, Carrier DJ, Clausen EC. Department of Chemical Engineering, University of  Arkansas, 3202 Bell  Engineering Center, Fayetteville, AR 72701, USA. Extraction of nutraceuticals from milk  thistle:  I.  Hot  water  extraction.  Appl  Biochem  Biotechnol.  2003 Spring;105    -108:881-9.    PMID:    12721425    [PubMed-indexed    for MEDLINE].

*Kvasnicka F, Biba B, Sevcik R, Voldrich M, Kratka J. Institute of Chemical Technology, Technicka 3, Prague 6, Czech Republic. Analysis of  the  active  components  of  silymarin.  J  Chromatogr  A.  2003  Mar 21;990(1-2):239-45. PMID: 12685603 [PubMed-indexed for MEDLINE].

*Gil’miiarova FN, Tutel’ian VA, Radomskaia VM, Gapparov MM, Kuznetsova OIu, Babichev AV, Kretova IG, Vinogradova LN, Baisheva GM, Gil’miliarov EM, Kleiman MS, Gergel’ NI, Vandyshev VV. Biological value  of  Silybum  marianum  oil.  Vopr  Pitan.  2002;71(4):32-5.  PMID: 12462953 [PubMed-indexed for MEDLINE].

*Pepping J. Kaiser Permanente, Honolulu, HI, USA. Milk thistle: Silybum marianum. Am J Health Syst Pharm. 1999 Jun 15;56(12):1195-7. PMID: 10484652 [PubMed-indexed for MEDLINE].

*Szentmihalyi K, Kery A, Lakatos B, Sandor Z, Petri G. MTA, Kemiai Kutatokozpont, Kemiai Intezet, Budapest. Determination of 23 elements in lady’s thistle (Silybum marianum L. Gaertner). Acta Pharm Hung. 1998 May;68(3):157-62. PMID: 9703702 [PubMed-indexed for MEDLINE]

*Morelli I. Constituents of Silybum marianum and their therapeutic use. Boll Chim Farm. 1978 May;117(5):258-67. PMID: 743375 [PubMed- indexed for MEDLINE].

*Takemoto T, Ikegawa S, Nomoto K. Studies on constituents of Silybum marianum (L.) Gaertn. I. New flavonolignans named 2,3- dehydrosilymarin  and  2,3-dehydrosilychristin.  Yakugaku  Zasshi.  1975 Aug;95(8):1017-21. PMID: 1237601 [PubMed-indexed for MEDLINE].

*Wagner H, Diesel P, Seitz M. The chemistry and analysis of silymarin from Silybum marianum Gaertn. Arzneimittelforschung. 1974 Apr;24(4):466-71. PMID: 4408125 [PubMed-indexed for MEDLINE].

*Holzl J. Biosynthesis and (14C) labelling of flavonolignans (silymarin) by Silybum marianum (Haller) (author’s transl). Z Naturforsch [C]. 1974 Jan-Feb;29(1):82-3. PMID: 4276432 [PubMed-indexed for MEDLINE].

*Halbach G, Gorler K. Separation of flavonoids from the fruits of St Mary’s distel (Silybum marianum). Planta Med. 1971 Apr;19(4):293-8. PMID: 5573540 [PubMed-indexed for MEDLINE].

*Schulte KE, Rucker G, Stigler H. Polyacetylenes as contents of Silybum marianum Gaertn. Arch Pharm Ber Dtsch Pharm Ges. 1970 Jan;303(1):7-17. PMID: 5265687 [PubMed-indexed for MEDLINE].

*Wagner H, Horhammer L, Seitz M. Chemical evaluation of a silymarin-containing flavonoid concentrate from Silybum marianum (L.) Gaertn.  Arzneimittelforschung. 1968  Jun;18(6):696-8.  PMID:  5755806 [PubMed-indexed for MEDLINE].

*Morazzoni P, Montalbetti A, Malandrino S, Pifferi G. Inverni della Beffa Research and Development Laboratories, Milan, Italy. Comparative pharmacokinetics of  silipide and  silymarin in  rats. Eur  J  Drug  Metab Pharmacokinet. 1993 Jul-Sep;18(3):289-97. PMID: 8149949 [PubMed- indexed for MEDLINE].

BIBLIOGRAFIJA

  • Real Farmacopea Española 2ª Edición (2002).
  • Pharmacopée Française IX Édition.
  • British Herbal Pharmacopoeia, 1983.
  • Herbal Drugs and Phytopharmaceuticals. Norman Grainger Bisset (Ed). Max Wichtl. CRC Press.1994.
  • Plantas Medicinales y Drogas Vegetales para infusión y tisana. Edición española a cargo de: Salvador Cañogueral, Roser Vila, Max Wichtl.1998.
  • Matière Médicale. RR Paris- H. Moyse. Masson 1981.
  • Fitoterapia: Vademecum de Prescripción. Plantas Medicinales. Colaboran: Asociación española de médicos naturistas. Colegio Oficial de Farmacéuticos de Vizcaya.
  • Guía de Campo de las Flores de Europa. Oleg Polunin. Edicione
  • Omega S.A. Barcelona, 1977.
  • Plantas Medicinales. Margarita Fernandez y Ana Nieto. Ed Universidad de Navarra. EUNSA 1982.
  • 100 Plantes Medicinales. Max Rombi. Romart 1998.
  • Fitoterapia Aplicada. J.B.  Peris,  G.  Stübing, B.Vanaclocha. ColegioOficial de Farmacéuticos de Valencia 1995.
  • Pharmacognosy,  Phytochemistry,  Medicinal  Plants.  Jean  Bruneton. Lavoisier Publishing.
  • The Complete German Commission E Monographs. Therapeutic Guide To  Herbal  Medicines.  Mark  Blumenthal.  American  Botanical  Council1998.
  • Revista de fitoterapia 2000. CITA Publicaciones y Documentación S.L.
  • Farmacognosia 2ª Edición. Jean Bruneton. Ediciones Acribia S.A. 2001.
  • Pharmacognosy 9th Edition.
  • Bulletin officiel Nº 90/22 bis. Ministère des Affaires Sociales et de laSolidarité.
  • French Public Health Code.
  • Bézanger-Beauquesne, L; Pinkas, M; Torck, M. Les Plantes dans la Therapeutique Moderne. 2ª. Paris: Maloine, 1986.
  • Bézanger-Beauquesne, L;  Pinkas,  M;  Torck,  M;  Trotin,  F.  Plantes Médicinales des Regions Tempérées. Paris: Maloine, 1980.
  • European Scientific Cooperative On Phytotherapy (E.S.C.O.P.). Monographs on the medicinal uses of  plant drugs. Fascicle I: Thymi herba. March, 1996.
  • James, A; Duke, Ph D. Handbook of Medicinal Herbs. 5ª. Boca Ratón, Florida: CRC Press, 1987, pp.170-1.
  • Paris, RR; Moyse, M. Précis de Matière Médicale. Tome III. Paris: Masson, 1971, p. 450.
  • Samuelsson, G. Drugs of Natural Origin. A Textbook of Pharmacognosy. Stockholm: Swedish Pharmaceutical Press, 1992, p.123.
  • Trease,    GE;    Evans,    WCh.    Farmacognosia.    México    D.F.: Interamericana–MacGraw-Hill, 1991, p. 450.
  • Van   Hellemont,   J.   Compendium   de   Phytotherapie.   Bruxelles: Association Pharmaceutique Belge, 1986, pp. 80-1.
  • Wichtl, M. Herbal Drugs and Phytopharmaceutical. A Handbook for Practice on a Scientific basis. Stuttgart: Medpharm Scientific Publishers,1994, pp. 121-5.
Deli na