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SCIENTIFIC NAME:
Silybum marianum Gaertn.
FAMILY NAME:
Asteraceae/Compositae
COMMON NAME:
Milk Thistle
  Evidence for Efficacy (Human Data)
   Clinical Trials  (45)
   Observational Studies/Case Reports  (19)
   Traditional and Folk Use  (20)
  Safety Data
   Adverse Effects & Toxicity  (6)
   Interactions  (7)
   Contraindications  (0)
  Evidence of Activity
   Animal Studies  (60)
   Pharmacodynamics  (107)
   Analytical Chemistry  (38)
   Pharmacokinetics (ADME)  (12)
   Genetics & Molecular Biology  (9)
  Formulas/Blends
   Modern Methods of Preparation  (13)
   Patents  (8)
   Folk Blends (component)  (0)
   Contemporary Mixtures (component)  (0)
  Other Information
   Pictures & Distribution Maps  (3)
   Cultivation, Conservation & Ecology  (9)
   Related Links  (7)
  Dynamic Updates
   Live PubMed Searches  (15)
  History of Records
   History of Record (1)
 
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EVIDENCE FOR EFFICACY (HUMAN DATA)
 
Clinical Trials
  Testing of a standardized silybin and soy phosphatidylcholine complex serum marker of iron status on 37 patients with chronic hepatitis C and Batts-Ludwig fibrosis stage II, III, or IV was associated with reduced body iron stores, especially among patients with advanced fibrosis stage. Bares 2008
  It is found that 13 g of oral silybin-phytosome daily, in 3 divided doses, appears to be well tolerated in patients with advanced prostate cancer and is the recommended phase II dose. Asymptomatic liver toxicity is the most commonly seen adverse event. Flaig 2007
  A placebo-controlled, parallel-arm, pilot study tested the effects of two naturopathic interventions including a combination botanical supplement with Silybum marinum over five menstrual cycles on sex steroid hormones and metabolic markers in 40 healthy premenopausal women. Greenlee 2007
  A study conducted in 85 patients revealed that silybin conjugated with vitamin E and phospholipids could be used as a complementary approach to the treatment of patients with chronic liver damage. Loguercio 2007
  Update of 2002 & 2005 Cochrane evidence-based review found no evidence supporting or refuting milk thistle for alcoholic and/or hepatitis B or C virus liver diseases. Rambaldi 2007
  Phyto-Female Complex, a herbal formula which includes standardized extracts of black cohosh, dong quai, milk thistle, red clover, American ginseng, is safe and effective for the relief of hot flushes and sleep disturbances in pre- and postmenopausal women, at least for 3 months' use. Rotem 2007
  Review of several trials on the effects of milk thistle for patients with liver diseases, cancer, hepatitis C, HIV, diabetes, and hypercholesterolemia revealed promising results in certain types of cancer and in liver diseases with minimal toxic or adverse effects. Tamayo 2007
  Study on the complementary and alternative medicine use by 76 patients chronically infected with hepatitis C virus shows that the most commonly used herb was Silybum marianum (milk thistle), reported by 10 of 76 patients (13.2%). White 2007
  13 g of oral silybin-phytosome, a commercially available formulation containing silibinin, daily, in 3 divided doses, appears to be well tolerated in patients with advanced prostate cancer and is the recommended phase II dose. Asymptomatic liver toxicity is the most commonly seen adverse event. Flaig 2006
  Repeated administration of silipide (silibinin with phosphatidylcholine) in patients with colorectal adenocarcinoma, was safe and achieved levels of silibinin of 0.3 to 4 micromol/L in the plasma, 0.3 to 2.5 nmol/g tissue in the liver, and 20 to 141 nmol/g tissue in colorectal tissue. Hoh 2006
  Silymarin marianum seed extract treatment in 51 type II diabetic patients for 4 months has a beneficial effect on improving the glycemic profile. Huseini 2006
  Silymarin compounds likely decrease serum transaminases in patients with chronic viral hepatitis, but do not appear to affect viral load or liver histology. Mayer 2005
  Based on high-quality trials, milk thistle does not seem to significantly influence the course of patients with alcoholic and/or hepatitis B or C liver diseases. Rambaldi 2005
  [Two-year results of a randomised double-blinded trial evaluating silymarin for chronic hepatitis C.] Strickland 2005
  Botanical supplements containing Citrus aurantium, milk thistle, or saw palmetto extracts appear to pose a minimal risk for CYP-mediated herb-drug interactions in 12 healthy humans. Gurley 2004
  Sylibum marianum is a well-tolerated plant extract associated with a decrease in liver chemistries but with no apparent effect on viral load when given for 4 weeks in 34 patients with a diagnosis of chronic hepatitis C who were not using antiviral therapy. Torres 2004
  Silybum marianum may have a protective effect in the inflammatory response to chronic hepatitis C, but no role as an antiviral agent. Torres 2004
  Silybum marianum is well tolerated in 24 subjects with chronic hepatitis C, but does significantly affect serum hepatitis C virus RNA, alanine aminotransferase levels, quality of life or psychological well-being of the subjects. Gordon 2006
  Treatment with milk thistle appears to be safe and well tolerated and it was found no reduction in mortality, in improvements in histology at liver biopsy, or in biochemical markers of liver function among patients with chronic liver disease. Jacobs 2002
  Prospective open-label drug interaction study found milk thistle in commonly administered dosages should not interfere with indinavir therapy in patients infected with the human immunodeficiency virus. Piscitelli 2002
  In patients with functional dyspepsia, the commercially available herbal preparation that included milk thistle fruit (Iberogast STW-5* and STW-5-S) improved dyspeptic symptoms significantly better than placebo.[Article in German] Madisch 2001
  Silymarin (150 mg/ three times per day) did not affect 2 year survival of alcoholics with cirrhosis in a randomized, double-blind study of 200 people Pares 1998
  Review of the evidence for silymarin-induced protection of liver functions Skottova 1998
  600 mg/d silymarin decreased fasting blood glucose levels, mean daily blood glucose levels, daily glucosuria and HbA1c levels after 4 months in a trial with 60 insulin-treated diabetics with alcoholic cirrhosis Velussi 1997
  Plasma level in 12 healthy volunteers ingesting 80 mg of silybin was 141 ng/ml free at 2.4 hr with 2 hr half life and 255 ng/ml conjugated at 3.8 hr Gatti 1994
  120 mg of silybin to 14 patients resulted in plasma peak of free silybin within 3 hr and declining to undetectable by 12th hour. total silybin peaks at 3-4 hr above 400 ng/ml, persisting Schandalik 1994
  120 mg silybin equivalents to 9 cholecystectomy patients found that biliary silybin concentrations were several-fold lower than those observed after intake of silipide Schandalik 1992
  6 months of silymarin to cirrhotic patients normalized the originally low T cell percentage and the originally high CD8+ cell [Article in Hungarian] Deak 1990
  60 patients treated with silymarin and amino-imidazol-carboxamid-phosphate had normalized levels of liver enzymes and other parameters Lang 1990
  6 months of 420 mg/d silymarin, in a double blind study of cirrhotic patients, restored the diminished superoxide dismutase activity of erythrocytes and lymphocytes [Article in Hungarian] Muzes 1990
  A 6 month double blind clinical trial with 36 patients showed normalization of serum bilirubin, aspartate aminotransferase and alanin-aminotransferase [Article in Hungarian] Feher 1989
  4-year survival rate was 58% in treatment group (140 mg silymarin 3 times daily) vs. 39% in placebo group in a double blind study of 170 cirrhosis patients Ferenci 1989
  14 type-II hyperlipidaemic outpatients treated with 420 mg Legalon daily for three months had decreased cholesterol and apolipoprotein Somogyi 1989
  Liver function tests and the platelet counts improved for 30 workers exposed to organic solvents taking Legalon compared with the 19 left without treatment Szilard 1988
  Legalon showd benefit in a double-blind trial with 180 hepatitis patients for 40 days Tanasescu 1988
  Legalon to 24 liver disease patients had good effect on thymol test, SGOT, gamma-globulins, immunoglobulin G, blood bilirubin without affecting subjective symptoms [Article in Bulgarian] Brailski 1986
  Decreased S-SGPT (S-ALAT) and S-SGOT (S-ASAT) was found in a 4 week placebo controlled trial of 106 liver patients Salmi 1982
  A randomized double-blind study about the therapy of the cirrhosis of the liver shows a significant higher surviving rate of the alcoholic cirrhosis in the group treated with Silymarin [Article in German] Benda 1980
  Milk thistle (Silybum marianum) derivatives in the therapy of chronic hepatopathies [Article in Italian] De Martiis 1980
  Silymarin, 2 x 70 mg 3 times daily, to 28 viral hepatitis patients showed beneficial influence on the characteristicly increased serum levels of bilirubin, GOT and GPT compared with 29 in the placebo group [Article in German] Magliulo 1978
  2 x 3 table analysis of liver biopsy data from a controlled clinical trial of silymarin in the treatment of chronic hepatitis Scheiber 1978
  Therapy of acute virus hepatitis with silymarin. Report of a controlled study [Article in German] Schmidt 1977
  Clinical investigation of silymarin in chronic liver diseases (author's transl) [Article in French] Realini 1975
  Clinical experience with silymarin in the treatment of chronic liver disease(author's transl) [Article in German] Reutter 1975
  Silymarin in chronic liver diseases [Article in German] Muscher 1972
Observational Studies/Case Reports
  Exacerbation of hemochromatosis by ingestion of milk thistle. Kidd 2008
  Exacerbation of hemochromatosis by ingestion of milk thistle. Whittington 2007
  [Milk thistle and chronic liver disease.] Hoofnagle 2005
  The anticancer and canceroprotective activities of silymarin and silybin were demonstrated in a large variety of illnesses of different organs as e.g., prostate, lungs, CNS, kidneys, pancreas and others. Kren 2005
  Milk thistle (Silybum marianum) is a botanical that may be useful in the prevention or treatment of liver dysfunction in patients undergoing anticancer therapy. Ladas 2003
  Silymarine improves the prognosis after accidental ingestion of the toxic Amanita phalloides & patients infected with hepatitis B and C might benefit from Silymarine. [Article in French] Laekeman 2003
  The beneficial effects of silymarin are most often seen in the patients who had cirrhosis as a result of alcohol abuse & it has a good safety record and only rare case reports of gastrointestinal disturbances and allergic skin rashes have been published. Bean 2002
  According to the scientific data, the mostly used plants for diabetes complications are Ginkgo biloba, Allium sativum, Silybum marianum, Panax Ginseng, Carica papaya, Vaccinium myrtillus, Phaseolus vulgaris. [Article in Lithuanian] Savickiene 2002
  Application of natursilum in dental surgery and in postoperative period promoted optimization of an implant osteointegration and normalized physicochemical and metabolic parameters of the oral liquid.[Article in Russian] Gil'miiarov 2001
  For primary biliary cirrhosis, eicosapentate and ursodeoxycholic acid may provide benefit to some patients while silymarin from milk thistle did not provide any additional benefit. Rosenthal 2000
  Adding Silybum to bread products is an effective medicine with general restorative influence, increasing internal protection resources, capacity for work and vital activity [Article in Russian] Gil'miiarov 1998
  A family poisoned by Amanita mushrooms had a turnabout for the better upon treatment starting the 3rd day with silibinin [Article in Italian] Carducci 1996
  No difference in 15 month mortality of alcoholic liver disease patients treated with 280 mg/day of Silymarin [Article in Spanish] Bunout 1992
  The basic therapy in alcoholic liver diseases includes well balanced nutrition and symptomatic treatment. Infusions with glucose-glucagon-insulin, or the administration of silymarin, and in individual cases of glucocorticoids seems to be justified [Article in German] Rink 1992
  Review of using milk thistle for gastrointestinal conditions, especially liver diseases Fintelmann 1991
  Bile cholesterol and the bile saturation index decreased by silibinin in 15 patients (420 mg per day for 30 days) or in rats (100 mg/kg for 7 days) Nassuato 1991
  A close relationship was found between the severity of the Amanita poisoning and the time elapsed before commencement of silybin therapy for 18 cases [Article in German] Hruby 1983
  Retrospective analysis of 205 Amanita poisoning cases indicates benefit of penicillin, hyperbaric oxygenation and silybin [Article in German] Floersheim 1982
         Database of evidence-based clinical practice guidelines from the Agency for Healthcare Research and Quality
Traditional and Folk Use
  Review on treatment of alcoholic liver disease indicates that complementary and alternative medicine agents such as zinc, milk thistle, and SAM have great therapeutic rationale. Barve 2008
  It is reasonable to employ silymarin as a supportive element in the therapy of Amanita phalloides poisoning but also (alcoholic and grade Child 'A') liver cirrhosis. Saller 2008
  Persons with chronic hepatitis C often use herbals, especially silymarin (milk thistle extract), hoping to improve the modest response to antiviral therapy and reduce side effects. Seeff 2008
  Milk thistle may have applications in ameliorating long-term hepatic and cardiovascular effects of cancer treatment. Greenlee 2007
  Silymarin (Silybum marianum [L.] Gaertn.) is a promising agent for cancer prevention, adjuvant cancer treatment, and reduction of iatrogenic toxicity. Sagar 2007
  Silybum marianum is a medicinal plant used widely for treating liver diseases. The silymarin, a mixture of three flavolignan isomers namely silybin, silydianin, and silychristin is an active constituent of the plant. Khan 2006
  A series of research on plants used in Calabria in the folk plant medicine was carried out in the last twenty years describes the use of 104 taxa distributed into 42 families including Silybum marianum for haemorrhoids. Passalacqua 2006
  Determination of types of alternative therapies used by liver transplant recipients shows that herbal products were used by 45% of the alternative therapy users and included milk thistle (silymarin), eclipta, and green beet leaf-all considered "hepatic tonics". Tickerhoof 2006
  The review focuses exclusively on published literature pertaining to the potential use of Silybum marianum or its derivatives for the treatment of alcoholic liver disease. Ball 2005
  Review on treatment of alcoholic liver disease indicates that some complementary and alternative medicinal agents, such as milk thistle and S-adenosylmethionine, may be effective in alcoholic cirrhosis. Bergheim 2005
  Review on herbal medicines for liver diseases shows that silymarin does not reduce mortality and does not improve biochemistry and histology among patients with chronic liver disease; however, it appears to be safe and well tolerated. Dhiman 2005
  Milk thistle has been used as a cytoprotectant for the treatment of liver disease, for the treatment and prevention of cancer, and as a supportive treatment of Amanita phalloides poisoning. Rainone 2005
  The use of herbal preparations including milk thistle, ginseng, and Echinacea is prevalent among veterans with chronic hepatitis C, especially those with higher levels of education and higher incomes. Siddiqui 2004
  Hepeel, a homeopathic remedy used to treat primary and secondary functional disorders of the liver contains diluted extracts from seven plants including Carduus marianus from Silybum marianum which showed antioxidative, antiproliferative and biochemical effects on HepG2 cells. Gebhardt 2003
  [By the way, doctor... My neighbor takes something called milk thistle. He likes to drink alcohol and believes the herb will protect him against any kind of liver damage. Is he right?] Lee 2001
  The extract from the seeds of Silybum marianum shows biological effects corresponding to nutritional supplements. [Article in Czech] Simanek 2001
  The eight most important supplements for people on HAART includes multi-vitamins, L-glutamine, alpha lipoic acid, and milk thistle. [No authors listed] 1999
         Info on milk thistle in David L. Hoffmann's Herbal Materia Medica
         St. Mary's Thistle in King's American Dispensatory
         European ethnobotanical info at Liber Herbarum II
SAFETY DATA
 
Adverse Effects & Toxicity
  Milk thistle is considered safe and well-tolerated, with gastrointestinal upset, a mild laxative effect, and rare allergic reaction being the only adverse events reported when taken within the recommended dose range. Post-White 2007
  [Toxicity. Milk thistle and indinavir.] [No authors listed] 2002
  The potential toxicity and safety of the Chinese herbal medicine NPI-028 in rats following subchronic (3-month) exposure via daily oral consumption was determined. Keyler 2002
  [Milk thistle: effects on liver disease and cirrhosis and clinical adverse effects.] Mulrow 2000
  Pharmacodynamics, site and mechanism of action of silymarin, the antihepatoxic principle from Silybum mar. (L) Gaertn. 1. Acute toxicology or tolerance, general and specific (liver-) pharmacology [Article in German] Vogel 1975
  On the pharmacology and toxicology of silymarin, an antihepatotoxic active principle from Silybum marianum (L.) Gaertn [Article in German] Hahn 1968
Interactions
  The clinical assessment of CYP2D6-mediated herb-drug interactions in humans were studied using milk thistle, black cohosh, goldenseal, kava kava, St. John's wort, and Echinacea. Gurley 2008
  Modulation of human cytochrome P450 3A4 and P-glycoprotein gene expression in Caco-2 cell monolayers by selected commercial-source milk thistle and goldenseal products can serve as an important marker for the in vitro assessment of NHP-drug interactions. Budzinski 2007
  The effect of extracts & individual constituents of goldenseal, Ginkgo biloba, grape seed, milk thistle, and ginseng on the activities of cytochrome P450 enzymes in human liver microsomes were determined revealing clearance of many drugs may be diminished due to inhibition of P450 enzymes. Etheridge 2007
  The drug-interaction potential of milk thistle extracts appears quite low, and silibinin appears to synergize with the antitumor effects of some commonly used chemotherapeutics. Kroll 2007
  The interactions of silybin with phosphatidylcholine bilayers were studied in detail using fluorescence spectroscopy, microcalorimetry and electron spin resonance techniques. Weso?owska 2007
  Review on possible drug-metabolism interactions of medicinal herbs with antiretroviral agents, indicates that echinacea, garlic, ginkgo, milk thistle, and St. John's wort have the potential to cause significant interactions. van den Bout-van den Beukel 2006
  Review on herb-drug interactions reveals that Silybum marianum (milk thistle) decreased the trough concentrations of indinavir in humans. Hu 2005
Contraindications
No Records
 
EVIDENCE OF ACTIVITY
 
Animal Studies
  An herbal mixture (HE) containing alder tree, labiate herb, milk thistle, green bean-rice bran fermentation plus added yogurt was tested in rats for its effect on ethanol-induced liver injury, showing that HE & yogurt reduced liver injury and resulted in a lower grade of lipid deposition. Baek 2008
  Study revealed that silymarin inhibited UV-induced oxidative stress through targeting infiltrating the CD11b+ cell type in C3H/HeN mouse skin. Katiyar 2008
  The restoration of the CCl(4)-induced hepatic fibrosis by high doses of silymarin in rats was investigated and the findings indicated that silymarin may have the potential to increase the resolution of the CCl4-induced liver fibrosis in rats. Tsai 2008
  Hypotheses that silibinin or silipide or silibinin formulated with phospholipids delay tumor development in TRAMP or Apc(Min) mice genetic models of prostate or intestinal malignancies was tested; results cautiously support advancement of silipide for clinical investigation in prostate cancer. Verschoyle 2008
  The hypothesis that consumption of silibinin or silipide, a silibinin formulation with pharmaceutical properties superior to the unformulated agent, affect breast cancer development in the C3(1) SV40 T,t antigen transgenic multiple mammary adenocarcinoma mouse model was tested. Verschoyle 2008
  The hepatobiliary excretion of silibinin and its effect on dimethylnitrosamine (DNM) -induced liver cirrhosis was examined and showed that the phase II conjugative reaction of silibinin was blocked by treatment with DNM. Wu 2008
  The potential for enhanced bioavailability (BA) of phytosome complex containing phosphatidylcholine & silybin, primary active flavonolignan in silymarin extract, was tested in dogs which revealed that phytosome complex of phosphatidylcholine & silybin markedly enhances BA in dogs. Filburn 2007
  The effects of IdB 1016, a complex of silybin with phosphatidylcholine, on the development of mammary tumors appearing spontaneously in HER-2/neu transgenic mice were investigated and its antitumor effect was confirmed. Provinciali 2007
  The effects of different doses of silymarin in diet on broiler performances and meat quality were studied which showed reduced lipid content of both breast and thigh and increased muscles resistance to oxidative stress. Schiavone 2007
  It is indicated that both systemic and local administration of silymarin was effective against burn-induced oxidative damage and morphological alterations in rat skin. Toklu 2007
  Silymarin and vitamin E decreased gentamicin-induced nephrotoxicity in dogs by their potentially beneficial antioxidant properties. Varzi 2007
  Numerous studies have indicated that silymarin is a chemopreventive agent in vivo against a variety of carcinogens/tumor promoters, including UV light, 7,12-dimethylbenz(a)anthracene , phorbol 12-myristate 13-acetate and others. Agarwal 2006
  The effect of hepatoprotective drug silymarin on body weight and biochemical parameters, particularly, antioxidant status of ethanol-exposed rats was studied and its efficacy was compared with the potent antioxidant, ascorbic acid as well as capacity of hepatic regeneration during abstention. Das 2006
  Dietary silymarin increased the plasma concentration of free and total silibinin, a major component of silymarin, in a dose-dependent manner in the rat, but did not decrease either mammary tumor incidence or number. Malewicz 2006
  Effect of Silymarin (SM) on enzymatic & non enzymatic antioxidant defensive systems in acetaminophen-induced damage in male albino rat bain was evaluated which revealed that SM protects SNC by oxidative damage by its ability to prevent lipid peroxidation & by replenishing GSH levels. Nencini 2006
  Silymarin is orally absorbed and is excreted mainly through bile as sulphates and conjugates. Silymarin offers good protection in various toxic models of experimental liver diseases in laboratory animals. Pradhan 2006
  Silibinin a flavanone from milk thistle inhibits lung tumor angiogenesis in urethane-induced lung tumors in mice which merits its investigation as a chemopreventive agent for suppressing lung cancer progression. Singh 2006
  Oral administration of deguelin in A/J mice reduced tumor multiplicity by 56% and tumor load by 78%, whereas silibinin treatment at doses of 0.05% and 0.1% in the diet did not show any significant efficacy on either tumor multiplicity or tumor load. Yan 2005
  The aqueous extracts of Fraxinus excelsior seed and Silybum marianum exhibit potent hypoglycaemic and anti-hyperglycaemic activities in normal and streptozotocin rats, respectively, without affecting basal plasma insulin concentrations. Maghrani 2004
  Silymarin and Prunella vulgaris improve antioxidant status in blood and liver and positively affect plasma lipoprotein profile in an experimental model of dietary induced hypertriglyceridemia using Hereditary hyper-triglyceridemic rats. Skottova 2004
  Daily administration of 10 g per animal of silymarin extract has no adverse effect on the liver of lactating cows, and presents no objective evidence for a hepatoprotective effect in this species. Tedesco 2004
  It is suggested that silymarin phytosome can provide protection against the negative effects of AFB1 on performance of broiler chicks. Tedesco 2004a
  Based on skeleton of silybin, flavones & coumarins containing 1,4-dioxane ring system were prepared & evaluated against carbon tetrachloride induced hepatotoxicity in rats which revealed that hydroxy methyl group at position-2" in dioxane ring exhibited superior antihepatotoxic activity. Ahmed 2003
  In vivo parenteral exposure to silymarin in male BABL/c mice results in suppression of T-lymphocyte function at low doses and stimulation of inflammatory processes at higher doses. Johnson 2003
  Silymarin retards the development of alcohol-induced hepatic fibrosis in 12 baboons, consistent with several positive clinical trials. Lieber 2003
  The study results suggest that alterations of TGFbeta1 and c-myc expression in the liver may be involved in the hepatoprotective effects of silymarin observed in other studies. He 2002
  The in vivo exposure to silymarin influences phenotypic selection processes in the thymus of male BABL/c mice at doses that may be encountered in natural medicinal use. Johnson 2002
  It was suggested that prevention of UVB-induced immuno-suppression and oxidative stress by silymarin may be associated with the prevention of photocarcinogenesis in mice. Katiyar 2002
  The effect of dietary administration of the polyphenolic antioxidant flavonoid silymarin, isolated from milk thistle [Silybum marianum (L.) Gaertneri], on azoxymethane -induced colon carcinogenesis was investigated in male F344 rats which revealed chemopreventive ability of dietary silymarin. Kohno 2002
  This study assessed in vivo growth inhibitory potential of silibinin against advanced human prostate cancer (PCA)and found in vitro anticancer effect of silibinin/silymarin in an in vivo preclinical PCA model. Singh 2002
  Findings suggest that silymarin is effective in preventing N-butyl-N-(4-hydroxybutyl)nitrosamine (OH-BBN) induced bladder carcinogenesis in mice. Vinh 2002
  Results indicate that feeding of silymarin (500 p.p.m.) during the promotion phase of 4-NQO-induced rat tumorigenesis exerts chemopreventive ability against tongue squamous cell carcinoma through modification of phase II enzymes activity, cell proliferation, and/or PGE(2) content. Yanaida 2002
  Legalon significantly increased the activity of superoxide dismutase in liver tissues, while the Saint-Mary thistle oil did not produce such effect. [Article in Russian] Batakov 2001
  Extracts from 9 plants including Silybum, singly & in a commercial formulation , STW 5 & its modified preparation, STW 5-II, were tested for their anti-ulcerogenic activity against indomethacin induced gastric ulcers of the rat as well as for their antisecretory & cytoprotective activities. Khayyal 2001
  To evaluate the use of radiolabeled silibinin, two derivatives, separated by HPLC after iodination ((125)I-SB(1) and (125)I-SB(2)) and their complexes 1:1 with phosphatidylcholine ((125)I-SPC(1) and (125)I-SPC(2)) were given with a single dose of 5.0 mg or 50 mg of silibinin per kg/wt to rats. Skottova 2001
  This study tests the capacity of silybin to protect the rat fetus from toxic effects of maternally ingested EtOH. Rats fed Silybin orally administered as Siliphos(R), which is one part silybin to two parts phosphatidylcholine found Gamma glutamyl transpeptidase activity was not elevated. Edwards 2000
  Silymarin exhibited significant antiinflammatory and antiarthritic activities in the papaya latex induced model of inflammation and mycobacterial adjuvant induced arthritis in rats. Results show action through inhibition of 5-lipoxygenase for antiinflammatory and antiarthritic activities. Gupta 2000
  Flavonoids of milk thistle, Silybum marianum fed to rats, reduced toxicity of T-2 toxin and was accompanied by reduction of a degree of change of activity of lysosomal enzymes and microsomal xenobiotic metabolizing enzymes. [Article in Russian] Kravchenko 2000
  In animals received T-2 toxin against a background of a diet with addition a flour from seeds of milk thistle with high contents of flavonoids, described morphological changes were expressed to a lesser degree than rats not fed milk thistle seed flour. [Article in Russian] Pozdniakov 2000
  The results suggest that silymarin offers high protective effects against tumor promotion, primarily targeted against stage I tumors, and the mechanism of such effects may involve inhibition of promoter-induced edema, hyperplasia, proliferation index, and oxidant state. Lahiri-Chatterjee 1999
  Test results showed social recognition scores recorded for the Sprague-Dawley rats pups on the ethanol diet were significantly poorer than those observed in both silymarin/ethanol groups and the chow group. Reid 1999
  Decoctions and infusions of medicinal plants (common barberry, sandy immortelle, common maize, spotted milk thistle) studied on free-radical oxidation (FRO) in vitro and in vivo on albino mice. In vivo tests found lipid perioxidation was suppressed. Ryzhikova 1999
  In vitro experiments with kidney cells damaged by paracetamol, cisplatin, and vincristin demonstrated that administration of silibinin before or after the chemical-induced injury can lessen or avoid the nephrotoxic effects. Sonnenbichler 1999
  The results of the study demonstrate the bioavailability of and phase II enzyme induction by systemically administered silibinin in different tissues, including skin, where silymarin has been shown to be a strong cancer chemopreventive agent. Zhao 1999
  Silymarin was better than silybin and as good as probucol at anticholesterolemic effect. It increases HDL and decreases liver cholesterol content in rats Krecman 1998
  Liver damage induced by thioacetamide, carbon tetrachloride, paracetamol or rifampicin was reduced by monomethyl fumarate (from Fumaria indica whole plant) as well as silymarin Rao 1998
  Silymarin (mixture of flavonolignans from seeds of Silybum marianum) caused mild increase in HDL cholesterol without change in serum cholesterol in rats Skottova 1998
  Sylimaryn-phospholipid complex to rabbits decreased serum total cholesterol, LDL, phospholipids and triglycerides and increased serum zinc and liver P450. A decrease of serum dimalonic aldehyde was followed by increase of ascorbyl free radicals in liver [Article in Polish] Bialecka 1997
  Silymarin protects against UVB and phorbol induced nonmelanoma skin cancer in mice Katiyar 1997
  Glucose/insulin were lowered by silibinin with rat pancreas in vitro but not in vivo von Schonfeld 1997
  Silymarin protects against skin tumors initiated by DMBA and promoted by TPA or okadaic acid and there is less TNF alpha mRNA Zi 1997
  Cisplatin induced kidney damage was ameliorated by silibinin pretreatment (200 mg/kg 1 hr before) in rats Gaedeke 1996
  The hepatoprotective activity of Picroliv (glycoside fraction of Picrorhiza kurroa) was comparable with that of silymarin against thioacetamide-induced injury to rats Dwivedi 1991
  A single dose of silymarin (flavonolignane) completely abolished the lethal effects to rodents of microcystin-LR, a hepatotoxin from blue-green algae, Microcystis aeruginosa Mereish 1991
  Silybum seed fed cows had slight increase in milk production [Article in Czech] Vojtisek 1991
  Silymarin increases the redox state and total glutathione content of the liver, intestine, and stomach of the rat but not in the kidney, lung, and spleen. Apparently there is entero-hepatic circulation Valenzuela 1989
  Bile stimulation by silybin Cavallini 1978
  Silymarin, 15 mg/kg 60 min before the toxin or 100 mg/kg 10 min after, is protects against phalloidine induced liver damage Desplaces 1975
  Silybine to rats (20 mg/kg) lowers systemic blood pressure, potentiates post-serotonine hypertension, inhibits ovalbumine induced anaphylactic shock and without change in vascular permeability [Article in French] Lecomte 1975
  Proceedings: Neutralization of the lethal effects of phalloidine and alpha-amanitine in animal experiments by substances from the seeds of Silybum marianum l. gaertn. Vogel 1974
Pharmacodynamics
  It was found that silibinin dose-dependently reduced glycolysis from carbohydrates in a cell perfusion system via an inhibitory effect targeted on pyruvate kinase activity. Detaille 2008
  The protective potential of Silibinin, the most active hepatoprotective constituent of Silybum marianum (milk thistle)?s seed, in liver transplantation injury was assessed and showed that silibinin protected the liver from cold preservation/warm reperfusion damages. Ligeret 2008
  It was shown that silibinin exerted a dose- and time-dependent inhibitory effect on the viability, motility and adhesion of highly metastatic human prostate adenocarcinoma cells. Mokhtari 2008
  Silymarin modulates imbalance between cell survival and apoptosis through interference with the expressions of cell cycle regulators and proteins involved in apoptosis. Ramasamy 2008
  Silymarin, like N-acetylcysteine, reduced sepsis-induced remote organ injury, at least in part, through its ability to balance oxidant-antioxidant status, to inhibit neutrophil infiltration, and to regulate release of inflammatory mediators in acute lung and brain injury. Toklu 2008
  The efficacy of the silymarins in inhibiting oxidized low-density lipoprotein (oxLDL) generation and subsequent scavenger receptor mediated monocyte adherence to oxLDL was reported. Wallace 2008
  The possible mechanism of the protective action of silymarin and silibinin, focusing on cancer therapies as agents causing cellular damage was discussed. Comelli 2007
  Discovery of the inhibition and modulation of drug transporters, P-glycoproteins, estrogenic receptors, nuclear receptors by silybin and some of its new derivatives contribute better understanding of silybin activity on the molecular level. Gaz?2007
  Silibinin significantly inhibits proliferation through cell-cycle arrest via inhibition of cyclin-CDK promoter activity. Apoptosis does not appear to be greatly increased in human colon cancer cell lines Fet, Geo, and HCT116. Hogan 2007
  The in vitro antioxidant properties & protective effects of silymarin in human erythrocyte haemolysates against benzo(a)pyrene [B(a)P], a carcinogenic chemical, was evaluated showing that silymarin possess protective effect and free radical scavenging action against environmental contaminants. Kiruthiga 2007
  Silymarin protected A375-S2 cell against UV-induced apoptosis was partially through SIRT1 pathway and modulation of the cell cycle distribution. Li 2007
  The effect of silymarin on anti-Fas agonistic antibody CH11-treated human malignant melanoma, A375-S2 cells was assessed and showed that silymarin could also exaggerate the apoptotic effect of anti-Fas agonistic antibody CH11 on A375-S2 cells. Li 2007a
  It is suggested that silymarin may protect the SNC by oxidative damage for its ability to prevent lipid peroxidation and replenishing the GSH levels. Nencini 2007
  Study indicates that Silymarin exerts anti-inflammatory and antiviral effects, and suggests complementary and alternative medicine-based approaches may assist in the management of patients with chronic hepatitis C. Polyak 2007
  Using 2 prostate cancer cell lines DU145 & 22Rv1, representing androgen-independent & androgen-dependent stages of malignancy, importance of p21 & p27 induction in silibinin-mediated G1 arrest was investigated and identified a central role of p21 & p27 induction & their role in cell cycle arrest. Roy 2007
  Silymarin was found to modify specifically the functions related to various transporters and receptors located in the cell membranes. Saller 2007
  Study suggests silymarin may be an effective agent in protecting hepatocytes from saturated fatty acids-induced cell death. Song 2007
  Silybin and 2,3-dehydrosilybin (1-50 micromol/l), flavonolignan components of Silybum marianum, were tested for their ability to moderate UVA-induced damage in HaCaT keratinocytes which showed that these flavonolignans suppress UVA-caused oxidative stress. Svobodov?007
  Twelve of 55 herbs were comparable to or exceeded oxygen radical absorbance capacity levels of milk thistle seed or tea leaf. The highest radical-scavenging activity was found in Olea europaea, Cimicifuga racemosa, Rheum palmatum, Glycyrrhiza glabra, and Scutellaria lateriflora. Wojcikowski 2007
  Silibinin protects cardiac myocytes against isoproterenol-induced injury through resuming mitochondrial function and regulating the expression of SIRT1 and Bcl-2 family members. [Article in Chinese] Zhou 2007
  Numerous agents identified from fruits and vegetables including curcumin, resveratrol (red grapes, peanuts and berries (apple, pears, prunes), silymarin (milk thistle), anethol can interfere with several cell-signaling pathways. Aggarwal 2006
  This review addresses in detail a number of recent studies showing a novel feature of silymarin as a hepatoprotective drug, namely: its anticholestatic properties in experimental models of hepatocellular cholestasis with clinical correlate. Crocenzi 2006
  The effects of various isoflavonoids and plant-derived extracts including Silybum marianum & Cimicifuga racemosa, on the hypothalamus-pituitary-thyroid axis is reviewed. Hamann 2006
  STW 5, a commercial preparation containing 9 extracts including milk thistle fruit and greater celandine herb, did not only lower the gastric acidity as effectively as the commercial antacid, but it was more effective in inhibiting the secondary hyperacidity. Khayyal 2006
  Microbial transformation of silybin A & B, the major hepatoprotective flavonolignan diastereomers from the fruits of Silybum marianum, with the culture broth of Trichoderma koningii gave two pairs of glucosylated derivatives. Their structures were identified by spectroscopic methods. Kim 2006
  Silymarin partially reduced UV-induced apoptosis in human malignant melanoma, A375-S2 cells by activating the Akt pathway, and silymarin's protective effect was also exerted by mitogen-activated protein kinase family members. Li 2006
  The protective effect of silibinin against UV irradiation in HaCaT cells is exerted by inactivation of caspase-8 after direct down-regulation of FADD expression, resulting in blockage of UV-induced apoptosis. Li 2006a
  The in vitro and in vivo research demonstrates that the 18 reviewed botanical medicines including Silybum marianum, Smilax glabra, etc. modulate the secretion of multiple cytokines. Spelman 2006
  The protective effects of silymarin, its flavonolignans silybin and dehydrosilybin and flavonoids quercetin and taxifolin against hydrogen peroxide-induced damage to human keratinocytes and mouse fibroblasts was investigated. Svobodova 2006
  Silibinin, a plant flavanoid from milk thistle protects against isoproterenol-induced rat cardiac myocytes injury through resuming mitochondrial function and regulating the expression of SIRT1 and Bcl-2 family members. Zhou 2006
  Silibinin, derived from the milk thistle plant, Silybum marianum, protected rat cardiac myocytes against isoproterenol-induced DNA damage through caspase pathway and the expression of p53, but independent on regulation of cell cycle. Zhou 2006a
  The inhibitory effect of silydianin, an active constituent of Silybium marianum, on the in vitro production and release of oxidative products has been examined. Zielinska-Przyjemska 2006
  It is suggested that the inhibition on MMP-2 and u-PA expression by silibinin may be through a suppression on ERK1/2 or Akt phosphorylation, which in turn led to the reduced invasiness of the cancer cells. Chen 2005
  Silibinin prevented taurolithocholate - and estradiol-17beta-d-glucuronide-induced bile salt secretory failure, at least in part, by avoiding redistribution of bile salt export pump, by a mechanism probably involving cAMP-induced cytosolic Ca(2+) elevations. Crocenzi 2005
  Silymarin and silibinin were shown for the first time to suppress the activity of the DNA topoisomerase IIalpha gene promoter in DU145 cells and, among the pure compounds, isosilybin B was again the most effective. Davis-Searles 2005
  Milk thistle may protect against cisplatin-induced renal toxicity in rats and might serve as a novel combination agent with cisplatin to limit renal injury. Karimi 2005
  Silymarin is a promising chemopreventive and pharmacologically safe agent which can be exploited or tested against skin cancer in human system and it may supplement sunscreen protection and provide additional anti-photocarcinogenic protection. Katiyar 2005
  Silibinin strongly inhibited growth of both HepG2 and Hep3B cells with a relatively stronger cytotoxicity in Hep3B cells, which was associated with apoptosis induction. Varghese 2005
  The ability of silymarin complex and its components to protect cardiomyocytes against doxorubicin-induced oxidative stress is due mainly to their cell membrane stabilization effect, radical scavenging and iron chelating potency. Chlopcikova 2004
  It is shown that silibinin treatment may decrease the expressions of metalloproteinase-2 and urokinase plasminogen activator in a concentration- and time-dependent manner and enhance the expression of tissue inhibitor of metalloproteinase-2. Chu 2004
  Review on risks or therapeutic opportunities of flavonoids shows that Soy, St. John's Wort, Silybum marianum, tea, etc. are medicinal plants containing flavonoids whose efficacy in treatment of a variety of diseases has been demonstrated in numerous clinical studies. [Article in Italian] Firenzuoli 2004
  Treatment with silymarin 500 microM for 12 h significantly inhibited UV irradiation (2.4 J/cm(2), 5 min)-induced apoptosis in human malignant melanoma cells (A375-S2 cells). Li 2004
  Well-known and newfound properties of milk thistle (Silybum marianum) preparations are considered (including hepatoprotector, immunostimulant, antiproliferative, antisclerotic, etc.) and the ways of their realization are analyzed. [Article in Russian] Samigullina 2004
  Silibinin inhibits in vivo lung tumor growth and reduces systemic toxicity of doxorubicin with an enhanced therapeutic efficacy via an inhibition of doxorubicin-induced chemoresistance involving NFkappaB signaling. Singh 2004
  The mechanisms of silibinin/ silymarin efficacy against prostate cancer involve alteration in cell cycle progression, and inhibition of mitogenic and cell survival signaling, such as epidermal growth factor receptor, insulin-like growth factor receptor type I and nuclear factor kappa B signaling. Singh 2004
  It has been observed that silibinin inhibits prostate tumor growth in animal models without any apparent signs of toxicity. Singh 2004a
  The cancer protective potential of silibinin, which down-regulates the co-activator of the androgen receptor, the prostate epithelium-derived Ets transcription factor and consequently the secretion of prostate-specific antigen was demonstrated. Thelen 2004
  The down-regulation of prostate specific antigen by silibinin and its counteraction on dihydrotestosterone effects indicate that this compound can interact with the expression of genes that are regulated through the androgen receptor. Thelen 2004a
  Callus and suspension cultures of Silybum marianum were derived and growth & production characteristics were assayed. The test for antioxidative activity against DPPH-radical demonstrated marked antioxidative properties of substances produced by culture of Silybum marianum. [Article in Czech] Tumova 2004
  The strongest synergistic effects for cell growth inhibition [combination index (CI) 0.35 for MCF-7 and 0.45 for MDA-MB468 cells] were evident at a silibinin dose of 100 microM plus 25 nM doxorubicin in both the cell lines. Tyagi 2004
  Silibinin modulates cyclin-dependent kinase inhibitors - cyclin-dependent kinase - cyclin cascade and activates caspase 3 causing growth inhibition and apoptotic death of human bladder transitional cell carcinoma cells. Tyagi 2004a
  The antioxidant activity of silybin might be due to its ability to inhibit protein kinase C translocation and NADPH oxidase activation in phorbol myristate actetate -stimulated neutrophils. Varga 2004
  The effect of silibinin in combination with cisplatin and carboplatin on human prostate cancer cells DU145 cell growth and apoptosis was investigated. Dhanalakshmi 2003
  The cytoprotective effects upon primary human hepatocytes of silymarin extract and its main flavonolignans following exposure to the cytotoxic actions of model toxins was evaluated. Dvorak 2003
  [Silibinin: a thorny therapeutic for EGF-R expressing tumors?] Hannay 2003
  Incubation of rat liver microsomes with preparations of grape flavonoids, dihydroquercetin, and silibinin increased their resistance to lipid peroxidation induced by NADPH-Fe2+. Kravchenko 2003
  Silybin has a potent antibacterial activity, more potent than silymarin II, against gram-positive bacteria without hemolytic activity, whereas it has no antimicrobial activity against gram-negative bacteria or fungi. Lee 2003
  Addition of silibinin was shown to inhibit epidermal growth factor receptor (EGFR) activation by EGF in 9L-EGFR cells which support the hypothesis that silibinin toxicity to cancer cells involves the EGFR signaling pathway. Qi 2003
  Silibinin significantly inhibited concanavalin A-induced liver disease and it proved to be an immune-response modifier in vivo, inhibiting intrahepatic expression of tumor necrosis factor, interferon-gamma, interleukin (IL)-4, IL-2, and iNOS, and augmenting synthesis of IL-10. Schumann 2003
  Silibinin is not resorbed by the chylomicron pathway, and the endogenous lipoprotein pathway VLDL --> LDL may play a role in the transport of silibinin from the liver to the extrahepatic tissues concurrently facilitating the lipoprotein antioxidant influence of silibinin. Svagera 2003
  Silymarin increased the external membrane fluidities of liver microsome and mitochondria, and decreased the internal membrane fluidities of liver microsome and mitochondria in mice. [Article in Chinese] Wu 2003
  Milk thistle (Silybum marianum) is a flowering herb utilized for its potentially protective effects on the liver and it concentrates in the hepatocytes and competes with toxins for hepatocyte binding and penetration. Boerth 2002
  Oil of Silybum Varianum is compared with the most widespread food oils. [Article in Russian] Gil'miiarova 2002
  The data data demonstrate that milk thistle extract can promote neuronal differentiation and survival, suggesting potential benefits of chemicals in this plant on the nervous system. Kittur 2002
  In contrast to quercetin, silybin, silydianin and silychristin did not chelate iron in aqueous solution. The results suggest that silymarin may prevent doxorubicin-mediated damage to rat heart membrane primarily through a free radical scavenging mechanism. Psotova 2002
  The study demonstrated that silibinin as well as silymarin induce growth inhibition and apoptosis in rat prostate cancer cells. Tyagi 2002
  It was found that Milk Thistle is immunostimulatory in vitro and it increased lymphocyte proliferation in both mitogen and mixed lymphocyte culture assays. Wilasrusmee 2002a
  Dong quai, ginseng, and milk thistle had nonspecific immunostimulatory effects on lymphocyte proliferation, whereas ginger and green tea had immunosuppressive effects. Wilasrusmee 2002b
  Effect of 4 flavonolignans: silybin, its hemisynthetic derivative dehydro-silybin, silydianin & silycristin on 3 specific cytochromes P450 activities were tested which showed dose-dependent inhibition with IC(50) values in micromolar range but inhibition is not considered to be relevant for therapy. Zuber 2002
  The in vitro effect of lyophilized Helichrysi flos extracts on microsomal lipid peroxidation was proved to be more effective compared to silibinin in examined concentrations. Czinner 2001
  Silymarin is a derivative from the milk thistle plant with few side effects used for centuries to treat liver ailments. Research results suggest silymarin has hepatoprotective, antiinflammatory, and regenerative properties producing a beneficial effect for some types of hepatitis. Giese 2001
  The outcomes, obtained in experiment, testify about high reparative ability of a natursilum.[Article in Russian] Gil'miiarova 2001
  The effect of silibinin, a component of Silybum marianum, on cellular differentiation was investigated in the leukemia HL-60 cell culture system. Silibinin enhanced protein kinase C (PKC) activity and increased protein levels of both PKCalpha and PKCbeta in 1,25-(OH)(2)D(3)-treated HL-60 cells. Kang 2001
  Silibinin, an active component of Silybum marianum, enhanced protein kinase C (PKC) activity and increased protein levels of both PKCalpha and PKCbeta in 1,25-(OH)(2)D(3)-treated human promyelocytic leukemia HL-60 cells. Kang 2001
  Several flavonoids obtained from barley leaves, soybean and some medicinal plants, Silybum marianum, Sophorae Flos, Cinnamon, Ephedrae Herba and Scutellariae Radix, were tested for their 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity. Okawa 2001
  Herbal medicines have been used for centuries and only recently been subjected to rigorous scientific scrutiny. Fever-few, milk thistle, tea tree oil, and valerian are considered safe for use by most patients. Where benefits occur, supporting evidence is inconclusive in some cases. Petry 2001
  The review covers the preparations of widely used herbs such as Silybum marianum, Phyllanthus amarus, P. kurroa, etc. as hepatoprotectants and includes the mode of action of these preparations. Ram 2001
  The objective of this review is to assess the clinical efficacy and safety of silymarin by application of systematic approach. Saller 2001
  Silymarin is considered to have mixed effects in human liver diseases. A Japanese herbal medicine Sho-saiko-to functions as a potent antifibrosuppressant. Understanding the mechanisms underlying the HCV-mediated fibrogenesis is valuable information for effective antifibrogenic therapies. Shimizu 2001
  Treatment with milk thistle extracts silymarin and silibinin alone or, more effectively in use with cysteine donors, benefit peritoneal macrophages of CAPD-patients due to a normalization and activation of the cellular thiol status followed by a restoration of specific functional capabilities. Tager 2001
  Flavonolignans inhibit the oxidative burst of PMNLs. This inhibitory effect depends on the chemical structure of the flavonolignans. Varga 2001
  Results showed the mixed commercial antioxidant, which suppressed lipid peroxidation and protected membrane proteins against degradation induced by peroxyl radicals, also effectively delayed AAPH induced haemolysis. Zou 2001
  Study results suggest that cell signaling and regulators of cell cycle are potential epigenetic molecular targets for prostate cancer prevention by such dietary agents that contain polyphenolic flavonoids and isoflavones such as those present in milk thistle, soy beans, and green tea. Agarwal 2000
  Iran grown Silybum marianum, Matricaria chamomilla, Calendula officinalis and Cichorium intybus extracted with 70% ethanol were found to enhance the proliferation of lymphocytes after stimulation with the allogenic cells. Amirghofran 2000
  Silibinin metabolism of erythromycin(CYP3A4), chlorzoxazone(CYP2E1), S(+)-mephenytoin(CYP2C19), caffeine (CYP1A2) or coumarin(CYP2A6)was minimal. Dextromethorphan metabolism(CYP2D6)was moderate. Denitronifedipine oxidation(CYP3A4;and warfarin 7-hydroxylation(CYP2C9) clear inhibition found. Beckmann-Knopp 2000
  Observations from this study point to the potential of silymarin to impair hepatic metabolism of certain coadministered drugs in humans. Venkataramanan 2000
  Study results suggest a mechanism by which silibinin acts as an antiproliferative agent and may justify further research for use of this compound or its derivatives in prostate cancer treatment and prevention. Zi 2000
  Silymarin extracted from the milk thistle is most widely subscribed to as a remedy for liver diseases. Evidence points to a potential, but unproven, benefit for this as well as other therapies based on free radical scavenger or antioxidant principles in treating patients with liver disease. Bass 1999
  Treatment of different prostate, breast, and cervical human carcinoma cells with silibinin resulted in a significant inhibition of cell growth and DNA synthesis. The study suggest that cancer chemopreventive and anti-carcinogenic effects of silymarin are due to the main constituent silibinin. Bhatia 1999
  Silybum marianum, inhibited in vitro the copper-induced oxidation of human LDL in a concentration-dependent manner. Silybin, a main flavonolignan of silymarin, appeared to be responsible for this LDL antioxidant effect. Skottova 1999
  Study results suggest that silibinin could be a useful agent for the intervention of hormone-refractory human prostate cancer. Zi 1999
  Review of history, pharmacology, and properties. Many studies on antioxidant activity but some also show it increases hepatocyte protein synthesis, decreases activity of tumor promoters, stabilizes mast cells and chelates iron metabolism Flora 1998
  Silybum marianum (milk thistle) has applications in the treatment of hepatitis, fatty liver, cirrhosis, ischemic injury, and radiation toxicity. The hepatoprotective effect of Picrorhiza kurroa was found to be similar, or superior to that of Silybum. Luper 1998
  In vitro dose-response curves for cisplatin combined with non-toxic silibinin doses did not deviate significantly from those of cisplatin alone indicating it may be useful to counter toxicity of chemotherapy Bokemeyer 1996
  Silibinin to rat Kupffer cells inhibited 02- and NO (IC50 80 microM) and LTB(4) (IC50 15 microM). No effect on TNF-alpha nor PGE(2) Dehmlow 1996
  Flow cytometry revealed that silybin decreased the percentage of cells in the S and G2-M phases of the cell cycle with a concomitant increase in cells in the G0-G1 phase. Silybin competes with estrogen for nuclear but not cytosolic Type II sites Scambia 1996
  Review of the possible biochemical mechanisms of activity of silymarin Valenzuela 1994
  Microsomes lipid peroxidation was inhibited, dose dependently, by all four flavanolignans tested: silicristin, silidianin, silybin and isosilybin Bosisio 1992
  Silibinin, 1-10 mcg/ml in vitro, enhanced the motility of polymorphonuclear leukocytes and, 2 hours after treating healthy volunteers, of leukocytes obtained from them Kalmar 1990
  Silymarin showed significant hepatoprotective activity in Plasmodium Berghei induced hepatic damage in Mastomys natalensis with protection of lipoprotein-X, GOT, GPT, alkaline phosphatase and bilirubin Chander 1989
  Silybin, a 3-oxyflavone, displays dose-dependent inhibition of in-vitro lymphocyte blastogenesis induced by lectins. CuSO4 prevents inhibition of PHA-induced proliferative response, suggesting a chelation mechanism Meroni 1988
  Silybin, silydianin and silychristin, are 12.66 to 52.06 times more active than theophylline and 0.77 to 3.17 times more active than papaverine at inhibition of cyclic AMP breakdown Koch 1985
  New antihepatotoxic effects of flavonolignans of a white flowering variety of Silybum [Article in German] Fiebig 1984
  Antihepatotoxic actions of flavonolignans from Silybum marianum fruits. Hikino 1984
  Changes in flourescence of microsomes treated with silymarin and silybyn suggest that they are incorporated into the hydrophobic-hydrophilic interface of the membrane bilayer and perturb the packing of acyl chains Parasassi 1984
  Silybin increased incorporation of choline into phosphatidyl choline by the postmitochondrial fraction of liver homogenates Schriewer 1979
  The dimer, disilybin, exhibits a phalloidin antagonistic activity at least 10 times that of silybin [Article in German] Vogel 1975
Analytical Chemistry
  Molecular descriptors such as CLogP, minimal cross-sectional area and polar surface area of 37 active components from selected herbal extracts such as milk thistle, kava, ginkgo, ginseng, valerian, black cohosh and garlic were estimated. Pade 2008
  Validation of high-performance thin-layer chromatographic methods for the identification of botanicals including green tea leaf, ginseng root, echinacea root, black cohosh rhizome, licorice root, kava root, milk thistle aerial parts and ginger root was carried out in a cGMP environment. Reich 2008
  Silymins A & B, the new pentacyclic triterpenes, have been isolated from ethyl acetate fraction of Silybum marianum and their structures assigned from (1)H and (13)C NMR spectra, DEPT and by 2D COSY, NOE and HMBC experiments. Ahmed 2007
  A hybrid chromatographic/ precipitative technique was developed, whereby silymarin mixtures were chromatographed at high concentrations to induce formation of a precipitate in the column fractions. Graf 2007
  The fragmentation behavior of (+)-silybin (1) and (+)-deuterosilybin (2), as well as of their flavanone-3-ol-type building blocks, were investigated by atmospheric pressure chemical ionization quadropole time-of-flight tandem mass spectrometry in the positive ion mode. K? 2007
  A sensitive method for the simultaneous quantitation of six active constituents including silydianin, silybin A and B, in commercial silymarin standardized extracts was developed based on liquid chromatography in combination with mass spectrometry. Lee 2007
  Investigations into the stability of tincture preparations of milk thistle fruit [ Silybum marianum L. Gaertn. (Asteraceae)] have led to the characterization of a new flavonolignan called silyamandin (1). MacKinnon 2007
  A comprehensive metabolomic profiling of Silybum marianum (L.) Gaernt cell cultures elicited with yeast extract or methyl jasmonate for the production of silymarin was carried out using one- and two-dimensional nuclear magnetic resonance spectroscopy. S?hez-Sampedro 2007
  Liquid chromatography-mass spectrometry IT-TOF can be useful for general screening of active natural products from plant extracts and for the specific quality control of silymarin. Shibano 2007
  A simple liquid chromatographic system was developed to assay silibinin in plasma and bile for pharmacokinetic study. Wu 2007
  Marianine, the new lanostane triterpene and marianosides A & B have been isolated from the whole plant of Silybum marianum. Their structures were elucidated on the basis of analysis of their one dimensional and two dimensional NMR spectral data. Ahmed 2006
  The metal content of 23 brands of dietary supplements, including black cohosh, echinacea, goldenseal, kava kava, milk thistle, saw palmetto, Synephrine, and valerian root was studied which revealed that none of 47 metals was found in highly toxic amounts in 23 brands of dietary supplements tested. Grippo 2006
  Six main active constituents, including silydianin, silychristin, were completely separated on a YMC ODS-AQ HPLC column. Lee 2006
  A new natural product silychristin B, has been isolated from silymarin, the hepatoprotective extract of milk thistle (Silybum marianum) fruits which was confirmed by NMR spectroscopy. Smith 2005
  With the help of spectrometry method higher content of flavolignans were detected in fortified butter (converting to silibin--the main component of "Liguid Extract Silybum marianum (L) Gaertn"). [Article in Russian] Spiridonov 2005
  A gradient HPLC-DAD-ESI MS method has been developed for simultaneous determination of multiple bioactive compounds such as abietane-type diterpenes, flavonolignans and phenolic compounds in compound preparations of Silybum marianum and Salvia miltiorrhiza. Zhao 2005
  A regioisomer of the known flavanolignan (-)-silandrin (3a), named (-) -isosilandrin (8a), was isolated from the fruits of a white-flowered variant of Silybum marianum L. populated in Hungary. Its structure was established both by spectroscopic methods and total synthesis. Samu 2004
  Complete separation, isolation, and structural characterization of four diastereoisomeric flavonolignans, silybins A & B, and isosilybins A & B from the seeds of milk thistle (Silybum marianum) were achieved for the first time using a preparative reversed-phase HPLC method. Kim 2003
  The content and composition of main silymarin components (silybin, isosilybin, silydianin and silychristin) in various pharmaceuticals were analysed using HPLC and newly developed capillary zone electrophoresis method. Kvasnicka 2003
  Two pairs of diastereoisomeric flavonolignans, silybin A, silybin B, isosilybin A, and isosilybin B, were successfully separated from Silybum marianum by sequential silica gel column chromatography, preparative reversed-phase HPLC, and recrystallization. Lee 2003
  The chemical stability of the active or marker constituents of Calendula flower, Milk-thistle fruit and Passion flower from accelerated and long-term testing by using HPLC was assessed. Bilia 2002
  A simple dissolution test developed to estimate silymarin in pharmaceutical formulations was described and the amounts dissolved range from 50 to 90% of the labeled value. Campodonico 2001
  The flavanolignan silybin was first oxidised to dehydrosilybin and then C-alkylated with either prenyl or geranyl bromide. The resulting isoprenoid dehydrosilybins were shown to display high in vitro affinities for direct binding to P-glycoprotein. Maitrejean 2000
  A new method of bioactivity-directed fractionation, based on multidrug resistant pump (MDR) inhibition in Staphylococcus aureus, was demonstrated. A natural flavonolignan, silybin (8) from Silybum marianum, was also shown to be a bacterial MDR pump inhibitor. Stermitz 2000
  The bioavailability of iron from local plants (black cumin seeds, milk thistle seeds, sesame seeds and thyme leaves) was investigated. Study found iron was better utilized from black cumin seeds as indicated by liver storage of iron. Jadayil 1999
  Determination of 23 elements in Silybum marianum [Article in Hungarian] Szentmihalyi 1998
  Naphtho-pyrone glycosides from Cassia tora seeds have greater hepato-protective effects against galactosamine damage than silybin Wong 1989
  Constituents of Silybum marianum and their therapeutic use [Article in Italian] Morelli 1978
  Tissue and suspension cultures of Silybum marianum. I. Communication: isolation and growth of tissue and suspension cultures and studies on flavonoids (author's transl)[Article in German] Becker 1977
  High-performance liquid chromatographic separation of silymarins and their determination in a raw extract of Silybum marianum Gaertn [Article in German] Tittel 1977
  Studies on constituents of Silybum marianum (L.) Gaertn. I. New flavonolignans named 2,3-dehydrosilymarin and 2,3-dehydrosilychristin [Article in Japanese] Takemoto 1975
  The chemistry and analysis of silymarin from Silybum marianum Gaertn [Article in German] Wagner 1974
  Polyacetylenes as contents of Silybum marianum Gaertn [Article in German] Schulte 1970
  Anatomy and histochemistry of the fruits of Silybum [Article in German] Langhammer 1969
  Chemical evaluation of a silymarin-containing flavonoid concentrate from Silybum marianum (L.) Gaertn[Article in German] Wagner 1968
         A validated method for detecting Silymarins in Milk Thistle by HPLC. Institute for Nutraceutical Advancement
         HPLC chromatogram of Silymarins in Milk Thistle. Institute for Nutraceutical Advancement
         Constituents of Silybum at Michael Moore's
Pharmacokinetics (ADME)
  In vitro evaluation and pharmacokinetics in dogs revealed that solid dispersion pellets containing Silybum marianum extract prepared by fluid-bed coating showed favorable in vitro characteristics and enhanced oral bioavailability. Sun 2008
  Study suggests that, after oral administration, silymarin flavonolignans are quickly metabolized to their conjugates, primarily forming glucuronides, and the conjugates are primary components present in human plasma. Wen 2008
  Study suggests that co-administration of silymarin does not considerably change the extent of absorption or metabolism of nifedipine but may decrease the absorption rate. Fuhr 2007
  The pharmacokinetics of pyrazinamide and pyrazinoic acid (PA) and their interaction with silibinin in rats were investigated and showed that the excretion pathway of PA may be blocked by silibinin through xanthine oxidase and hepatobiliary excretion. Wu 2007
  Compared with rifampin and clarithromycin, supplementation with the specific formulations of milk thistle or black cohosh did not appear to affect digoxin pharmacokinetics, suggesting that these supplements are not potent modulators of P-gp in vivo. Gurley 2006
  The effects of milk thistle, black cohosh, rifampin, and clarithromycin on midazolam pharmacokinetics were determined using noncompartmental techniques. Gurley 2006a
  The intake of milk thistle, Echinacea species, and goldenseal inhibits cytochrome P450 enzymes in vitro and may increase antiretroviral drugs concentrations, but by clinically unimportant amounts. Lee 2006
  Investigation of the intestinal absorption of silybin (SLB) in male rats showed that SLB can be absorbed in whole intestinal sections & when the concentration raises to a certain level, the uptake of SLB will not increase. [Article in Chinese] Luan 2006
  Silybin is the most potent of the flavonoids in milk thistle, but it is not well-absorbed. Silybin-phosphatidylcholine complexed as a phytosome provides significant liver protection and enhanced bioavailability over conventional silymarin. Kidd 2005
  Indinavir levels were not reduced significantly in the presence of milk thistle in a three-period, randomized controlled trial with 16 healthy participants. Mills 2005
  Silybin concentrations after intake of milk thistle are too low to significantly affect the function of CYP3A4 and UGT1A1 in vivo, indicating that milk thistle is unlikely to alter the disposition of anticancer drugs metabolized by these enzymes. van Erp 2005
  Evaluation of Indinavir's pharmacokinetic parameters at steady state both before and after administration of 14 days of silymarin shows that silymarin has no apparent effect on indinavir plasma concentration. DiCenzo 2003
Genetics & Molecular Biology
  The known sequence of events that regulate cell cycle progression with an emphasis on the checkpoints and the mechanisms cell employ to insure DNA stability in the face of genotoxic stress was studied using the dietary agents including genistein (soybean), and silymarin (milk thistle). Meeran 2008
  Phenotypic and genotypic coefficient of variability, heritability in broad sense and genetic advance were determined investigating the characters of 15 accessions of Silybum marianum. Ram 2005
  The inhibition of activation of NF-kappa B and the kinases may provide in part the molecular basis for the anticarcinogenic and anti-inflammatory effects of silymarin, and its effects on caspases may explain its role in cytoprotection. Manna 1999
  Silymarin inhibited ligand-induced activation of EGFR, associated with blocking kinase activity, and of tyrosine phosphorylation of Shc, an immediate downstream target of EGFR. Cells treated with silymarin also showed a significant G2-M arrest Ahmad 1998
  Silymarin inhibits activation of erbB1 signaling and induces cyclin-dependent kinase inhibitors, G1 arrest, and anticarcinogenic effects in human prostate carcinoma cells Zi 1998
  Induction of G1 arrest through an increase in Cip1/p21 concomitant with a decrease in kinase activity of cyclin-dependent kinases by silymarin in human breast cancer cells Zi 1998
  Silybin, silydianin and silychristin brought about a concentration-dependent non-competitive inhibition of soy lipoxygenase Rui 1991
  Silybin decreased incorporation of 14C-acetate or 3H2O in fatty acids. It also inhibits acetyl-CoA-carboxylase, fatty-acid-synthetase, ATP-citrate-lyase and NADP-malate-dehydrogenase suggesting it is unspecific. [Article in German] Schriewer 1979
  Incorporation of orotic acid into RNA of rat livers is stimulated by the flavonolignane derivative silybin [Article in German] Sonnenbichler 1976
FORMULAS/BLENDS
 
Modern Methods of Preparation
  Pretreating the milk thistle seed meal with 1.5% H2SO4 (w/w) at 50 degrees C for 18 h increased the silymarin yield which could replace the petroleum ether pretreatment. Subramaniam 2008
  Pressurized hot water can be used to extract flavonolignans from milk thistle and these extracts may possess therapeutic potential different from or beyond that of traditional organic solvent preparations. Wallace 2007
  The possible effect of poly (ethylene glycol) concentration and temperature on the solubility of silybin, a main component in silymarin was investigated and the solubilization capacity of the polymer for the drug was revealed. Bai 2006
  The stabilized formula of silymarin hybrid liposomes was evaluated upon buccal administration regarding its hepatoprotective activity against carbon tetrachloride-induced oxidative stress in albino rats. El-Samaligy 2006
  Investigation of lyophilization of silymarin-loaded solid lipid nanoparticles showed that the mixture of 2% lactose and 2% glucose could better prevent nanoparticles from aggregating. [Article in Chinese] He 2005
  Study on substantiating the potential use of flavolignans of Silybum marianum (L.) Gaertn. to create a new fat product-butter fortified by an "Liguid extract Silybum marianum (L.) Gaertn." are discussed. [Article in Russian] Spiridonov 2005
  Extraction & partial characterization of the aspartic proteolytic activity present in flowers of Silybum marianum was carried out and the hydrolytic profile of bovine caseins was evaluated. Vairo-Cavalli 2005
  When extracting with boiling water, the yields of silychristin, silybinin A & B were 380, 47 and 50% higher for whole seeds of milk thistle (Silybum marianum) compared with defatted seeds. Wallace 2005
  The use of hot water as an extraction solvent for milk thistle at temperatures above 100 degrees C was explored. The maximum extraction yield of each of the silymarin compounds and taxifolin did not increase with temperature. Duan 2004
  The batch extraction of silymarin compounds from milk thistle seed meal in 50, 70, 85, and 100 degrees C water as a function of time was examined. Barreto 2003
  In extracting defatted milk thistle seeds with organic solvents, extraction with ethanol resulted in the highest silymarin yield, although some potential degradation was observed. Wallace 2003
  The determination of the encapsulation efficiency of silybin liposomes showed that the efficiency ranged from 65.1%-83.0% when the drug/phospholipid ratio varied from 0.02-0.06. [Article in Chinese] Yu 2003
  Seven silymarin products were analysed for their ingredients, especially silibinin (CAS 22888-70-6) [Article in German] Schulz 1995
Patents
         Conduct a search on "Silybum marianum" or "Milk thistle" in the title, abstract or claims section of the US patent database
         L-ergothioneine, milk thistle, and S-adenosylmethionine for the prevention, treatment and repair of liver damage US Patent 6,863,906
         Health food useful for preventing liver and biliary dysfunctions containing an alkanoyl L-carnitine and Silybum marianum extract US Patent 6,552,070
         L-ergothioneine, Milk thistle, and S-adenosylmethionine for the prevention, treatment and repair of liver damage US Patent 6,555,141
         Process for isolation of hepatoprotective agent silymarin from the seeds of the plant Silybum marianum US Patent 6,309,678
         Method of treating liver diseases using pure silibinin US Patent 4,871,763
         Cosmetic preparations useful for opposing skin aging containing an extract of the fruits of Silybum marianum US Patent 4,749,573
         Polyhydroxyphenylchromanones US Patent 4,081,529
Folk Blends (component)
No Records
 
Contemporary Mixtures (component)
No Records
 
OTHER INFORMATION
 
Pictures & Distribution Maps
         A collection of milk thistle photos at CalPhotos
         Plant pictures by Henrietta Kress
         Plant picture at Michael Moore
Cultivation, Conservation & Ecology
  Formation of flavanolignane in the white-flowered variety (Szibilla) of Silybum marianum in relation to fruit development was studied. [Article in Hungarian] B? 2007
  It was found that seed germination of milk thistle, within 3-4 days was high (96%, except for striated seeds) and exposure to light significantly reduced sprout growth and significantly increased the polyphenol content and antioxidative capacity. Vaknin 2007
  The involvement of peroxidases from cell extracts, and suspension culture from media in silymarin turnover in cell cultures as well as the influence of elicitation on the activity towards several substrates was investigated. Sanchez-Sampedro 2006
  It is suggested that inhibition of external and internal calcium fluxes plays a significant role in flavonolignan metabolism of Silybum marianum cell cultures. Angeles Sanchez-Sampedro 2005
  It is indicated that elicitor treatment promotes secondary metabolite production in Silybum marianum cultures and that jasmonic acid and its functional analogue plays a critical role in elicitation. Sanchez-Sampedro 2005
  The rosette and cauline leaves of the highly thorny winter annual plant species of the Asteraceae in Israel (Silybum marianum) resemble green zebras. Lev-Yadun 2003
  Silybin, isosilybin, silychristin and silydianin were found in untransformed root cultures, by means of TLC and HPLC. In contrast, only isosilybin and traces of silychristin and silydianin were identified in the 'hairy' root cultures. Alikaridis 2000
         A bit of info on Silybum (scroll down a page, there's no direct link) at NewCROP
         Distribution map and other info in the PLANTS National Database
Related Links
         Search for "silybum" at Citeline.com
         A detailed description of milk thistle by Michelle Giesler and Kimberly Jones at Chad Bradshaw's Complementary and Alternative Medicine
         Milk thistle report at ConsumerLab.com
         Monograph at NCCAM Herbs-at-a-Glance
         Search for Silybum marianum in Dr. Duke's Phytochemical and Ethnobotanical Databases. Phytochem and Ethnobot DB
         Silybum marianum in The HortiPlex Plant Database
  Scroll down index of herbs to find Fructus Silybi Mariae within the pdf file in WHO monograph
DYNAMIC UPDATES
 
Live PubMed Searches
  Silybum marianum and Analytical Chemistry
  Silybum marianum and Animal Studies
  Silybum marianum and Case Reports
  Silybum marianum and Clinical Trials
  Silybum marianum and Drug Interactions
  Silybum marianum and Ethnobotanical Use
  Silybum marianum and Genetics
  Silybum marianum and In Vitro Studies
  Silybum marianum and Pharmacodynamics
  Silybum marianum and Pharmacokinetics
  Silybum marianum and Preparation & Formulary
  Silybum marianum and Reference Standards
  Silybum marianum and Safety & Toxicology
  Silybum marianum and Therapeutic Activity
  Silybum marianum and Tissue Culture

HISTORY OF RECORD
RESEARCHED BY: Soaring Bear, Ph. D.    1998
RESEARCH UPDATED BY: Michael Tims, Ph. D. cand.    2001
REVISED BY: J Mohanasundaram, MD, PhD    July 2008
 
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