Silybum marianum (L.) Gaertn.

Last updated: 2 June 2016

Scientific Name

Silybum marianum (L.) Gaertn.  

Synonyms

Carduus lactifolius Stokes, Carduus mariae Crantz, Carduus marianus L., Carduus versicolor Salisb,. Carthamus maculatus (Scop.) Lam., Centaurea dalmatica Fraas, Cirsium maculatum Scop., Mariana lactea Hill, Mariana mariana (L.) Hill [Illegitimate], Silybum maculatum (Scop.), Moench Silybum mariae (Crantz) Gray, Silybum pygmaeum Cass. [1]

Vernacular Name

English Milk thistle [2], blessed- milk thistle, blessed thistle, holy thistle, lady’s thistle, mary’s thistle, our lady’s milk thistle, st mary thistle, variegated thistle [3]
America Cardo de maria, cardo lechero, cardo santo, lechal (South) [3]; blessed milkthistle, cahrdon marie (North) [3]
China Shui fei ji [3]
Saudi Arabia Shouk-el-gamal, shouk sinnari, shouk el-gemal [3]
Africa Boerkwadissel, disseldoring, gevlekte silybum, mariendissel, melkdissel [3]
Spain Cardo de la alameda [3]

Geographical Distributions

Silybum marianum is native to Europe, southern Russia, America and Australia. [4]

Botanical Description

S. marianum is a member of Compositae family. S. marianum is an annual to biennial herb, up to 2 m high. It has a stem 20-150 cm high. [4]

The leaves are large, alternate, and white veined. [4]

The inflorescences are round and large. [4]

The florets are tubular in shape with a red-purple corolla. [4]

The fruits are hard skinned achenes 6 to 8 mm long and brownish in colour. [4]

Cultivation

No documentation

Chemical Constituent

S. marianum has been reported to contain silymarin (consisting of the flavonoids silibinin, isosilybin, silydianin and silychristin). [5]

Plant Part Used

Seed [4]

Traditional Use

No documentation

Preclinical Data

Pharmacology

Hepatoprotection

The constituents of milk thistle with hepatoprotective activity are a combination of flavonoids collectively termed silymarin. There have been a number of human clinical trials demonstrating the efficacy of milk thistle as a hepatoprotective agent. [6][7] The mechanism of silymarin’s reported hepatoprotective activity includes inhibition of the transport of toxins into the liver cells, enhanced liver detoxification via inhibition of Phase 1 detoxification, enhanced glucuronidation, stabilization of the hepatic cell membranes, stimulation of new liver cell regeneration through increased protein synthesis, selective inhibition of leukotriene formation by Kupffer cells, and inhibition of membrane peroxidation. [8][9][10] Silymarin has been demonstrated to increase glutathione content in the liver by more than 35 percent, increasing its antioxidant capacity. [11]

Milk thistle is also reported to inhibit the inflammatory leukotrienes, which increased levels may normally lead to the destruction of liver tissue. [13] Inhibition of NF-kappa B and kinase activation may provide in part the molecular basis for the anticarcinogenic and anti-inflammatory effects of silymarin. [14] Also, 5-lipoxygenase inhibition contributes to milk thistle’s antiinflammatory and antiarthritic activities. [15]

Milk thistle’s most celebrated use is in the antidoting of death cup mushroom poisoning. [16][17] If administered before the poisoning, it is claimed to be 100 percent effective. In animal studies, even if given as much as 24 hours after the poison was ingested, it exerted hepatoprotective properties and prevented death. [16] Because of its reported liver enzyme and cell protection capabilities, it is used in a wide variety of conditions, such as chemical-induced liver damage (including industrial chemicals, alcohol and pharmaceutical drugs), hepatitis, gallbladder dysfunctions, and psoriasis. [18][19] Studies have reported protective benefits in liver function in alcoholics and viral hepatitis. [20][21] Another study reported that silymarin reduced the side effects of various classes of psychotropic drugs through protection of the liver and reduction of liver enzyme induction. [22] A standardized milk thistle product was recently reported to protect liver damage induced by acetaminophen (Tylenol) poisoning. [23][24] A small pilot study found that milk thistle extract did not affect serum hepatitis C virus RNA, alanin aminotransferase levels or well-being in patients with Hepatitis C. [25]

A 2008 systmatic review with meta-analysis for the clinical evidence of milk thistle extract found that enough evidence exists to employ silymarin as a supportive element in the therapy of Amanita phalloides poisoning and also (alcoholic and grade Child 'A') liver cirrhosis. [26] A 2007 Cochrane Database System Review looked at 18 human trials in 1008 patients and found liver-related mortality was significantly reduced by milk thistle in all trials, but not in high-quality trials. [27]

Of interest are a few laboratory animal studies which suggest that fetal damage resulting from maternal alcohol and drug consumption may be limited when the mother is administered standardized milk thistle products. [28]

Studies also suggest that silymarin may protect against genomic injury, decrease the activity of tumor promoters, stabilize mast cells, chelate iron, and slow calcium metabolism. [29] Silibinin has been reported in laboratory studies to have anti-cancer activity on various human cancer cell lines. [30][31][32] Silibinin was found to inhibit hypoxia-inducible factor-1alpha (HIF-1alpha) expression in prostate cancer cells in vitro. [33] An in vitro study using human colon cancer cells found that silibinin significantly inhibits proliferation through cell-cycle arrest via inhibition of cyclin-CDK promoter activity. [34] Laboratory trials also suggest milk thistle modulates imbalance between cell survival and apoptosis through interference with the expressions of cell cycle regulators and proteins involved in apoptosis, as well as anti-inflammatory, anti-metastatic, and chemo/radioprotective effects. [35][36] Silibinin has been reported to modulate insulin-like growth factor (IGF) system by increasing circulating levels of IGF-binding protein 3 (IGFBP-3) and decreasing levels of IGF-I. [37]

In vitro experiments with kidney cells damaged by paracetamol, cisplatin, and vincristin and then treated with isolated silibinin before or after the chemical-induced injury, reported a decrease in the nephrotoxic effects of these toxic agents. [38]

Antioxidant activity

Silbinin’s antioxidant activity has been reported to modulate many molecular changes caused by xenobiotics and ultraviolet radiation to protect the skin, leading the industry to use silibinin in cosmetics as a novel antioxidant. [39] UV protection involves activation of the SIRT1 pathway, inactivation of caspase-8 pathway and modulation of the cell cycle distribution. [40][41]

 Galactagogue activity

Milk thistle has been reported to have galactagogue activity in animals and humans. A small human study found that women orally treated for 63 days with milk thistle showed a clear galactagogue role for the product with daily milk production increasing 86% vs. placebo at 32%. [42]

The liver plays an important role in regulation of metabolism of plasma lipoproteins, and liver injury is often reflected as a secondary dyslipoproteinaemia, which may lead to the development of atherosclerosis, particularly when associated with hypercholesterolaemia. Due to the inhibition of lipid peroxidation by silymarin as reported in the literature, milk thistle has also been reported to be a possible new agent in hypercholesterolemia. A laboratory animal study found that the cholesterol lowering effect of silymarin was parallel to that of probucol (dose-dependent). [43] Unlike probucol, however, silymarin caused an increase in high density lipoprotein (HDL)-cholesterol, a decrease in liver cholesterol content, and partially prevented the HCD-induced decrease in liver reduced glutathione, which are all of benefit in patients with hypercholesterolemia. Results suggest that silymarin’s hypocholesterolemic activity could be due to an inhibition of cholesterol biosynthesis and/or by inhibiting of resorption of dietary cholesterol. [44][45][46] Milk thistle’s antioxidant activity has also been reported to decrease LDL oxidation in laboratory studies. [47]

In a 4 month, randomized, double-blind placebo controlled human trial in 51 patients with Type 2 diabetes, milk thistle was reported to produce a significant decrease in HbA(1)c, FBS, total cholesterol, LDL, triglyceride, SGOT and SGPT levels compared with placebo. [47]

Toxicity

No documentation

Clinical Data

Clinical findings

No documentation

Precautions

Milk thistle may have a laxative effect. Patients who are allergic to plants in the Astreracaea/ composite family should be cautious about using milk thistle. [47][48]

Side effects

No documentation

Interaction & Depletion

Medications metabolized by the CYP-3A4 isoenzyme system and P-glycoprotein. [49] However, a small human study found that co-administration of silymarin and nifedipine does not considerably change the extent of absorption or metabolism of nifedipine (calcium channel blocker) but may decrease the absorption rate, suggesting silymarin is not a potent CYP3A4 inhibitor in vivo. [50]

Contraindications

No documentation

Case Report

No documentation

Dosage

Dosage Range

150mg twice a day and increase to 3 times/ day if needed. [48]

Most Common Dosage

150mg twice a day and increase to 3 times/ day if needed. [48]

Standardisation

No documentation

Poisonous Management

No documentation

Line drawing

No documentation

References

  1. The Plant List. Ver1.1. Silybum marianum (L.) Gaertn.  . [homepage on the Internet]. c2013 [updated 2012 Feb 11; cited 2016 June 3]. Available from: http://www.theplantlist.org/tpl1.1/record/gcc-114114
  2. Jane MD, Zachary IH. Thomson Delmar learning's pharmacy practice for technicians. New York: Cengage Learning, 2005; p. 372.
  3. Quattrocchi U. CRC World Dictionary of Plant Names: Common names, scientific names, eponyms, synonyms, and etymology. Volume I A-C. Boca Raton, Florida: CRC Press LLC, 2000; p. 391.
  4. International Union for Conservation of Nature (IUCN). A guide to medicinal plants in North Africa. Malaga, Spain: IUCN Centre for Mediterranean Cooperation, 2005; p. 221-224
  5. Wichtl M, editor. Herbal drugs and phytopharmaceuticals. Stuttgart: Medpharm Scientific Publishers, 1994; p. 121-123.
  6. Ferenci P, Dragosics B, Dittrich H, et al. Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. J Hepatol. 1989;9(1):105-113.
  7. Fuhr U, Beckmann-Knopp S, Jetter A, Lück H, Mengs U. The effect of silymarin on oral nifedipine pharmacokinetics. Planta Med. 2007;73(14):1429-1435.
  8. Rue YC. Advances in pharmacological studies of silymarin. Mem Inst Oswaldo Cruz. 1991;86(Suppl 2):79-85.
  9. Dehmlow C, Erhard J, de Groot H. Inhibition of kupffer cell functions as an explanation for the hepatoprotective properties of silibinin. Hepatology. 1996;23(4):749-754.
  10. Campos R, Garrido A, Guerra R, Valenzuela A. Silybin Dihemisuccinate Protects Against Glutathione Depletion and Lipid Peroxidation Induced by Acetaminophen on Rat Liver. Planta Medica. 1989;55:417-419.
  11. 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 Medica. 1989;55:1550-1552.
  12. Sonnenbichler J, Scalera F, Sonnenbichler I, et al. Stimulatory effects of silibinin and silicristin from the milk thistle silybum marianum on kidney cells. J Pharmacol Exp Ther. 1999;290(3):1375-1383.
  13. Fiebrich F, Koch H. Silymarin, an inhibitor of prostaglandin synthetase. Experimenta. 1979;35:150-152.
  14. Manna SK, Mukhopadhyay A, Van NT, Aggarwal BB. Silymarin suppresses TNF-induced activation of NF-kappa b, c-Jun N-terminal kinase, and apoptosis. J Immunol. 1999;163(12):6800-6809.
  15. Gupta OP, Sing S, Bani S, et al. Anti-inflammatory and anti-arthritic activities of silymarin acting through inhibition of 5-lipoxygenase. Phytomedicine. 2000;7(1):21-24.
  16. Vogel G, Tuchweber B, Trost W, Mengs U. Protection by silibinin against Amanita phalloides intoxication in beagles. Toxicol Appl Pharmacol. 1984;73:355-362.
  17. Desplaces A, Choppin J, Vogel G, Trost W. The effects of silymarin on experimental phalloidine poisoning. Arzneimitteforschung. 1975;25:89-96.
  18. Schopen RD, Lange OK. Therapy of hepatoses. Therapeutic use of silymarin. Med Welt. 1969;21:691-698.
  19. Valenzuela A, et al. Silymarin protection against hepatic lipid peroxidation induced by acute ethanol intoxication in the rat. Biochem Pharm. 1985;34:2209-2212.
  20. Varga M, Buris L, Fodor M. Ethanol elimination in man under influence of hepatoprotective silibinin. Blutalkohol. 1991;28(6):405-408.
  21. El-Kamary SS, Shardell MD, Abdel-Hamid M, et al. A randomized controlled trial to assess the safety and efficacy of silymarin on symptoms, signs and biomarkers of acute hepatitis. Phytomedicine. 2009;16(5):391-400.
  22. Carrescia O, Benelli L, Saraceni F, Braga PC, Cagnetta G, Copponi V. Silymarin in the prevention of hepatic damage by psychopharmacologic drugs. experimental premises and clinical evaluations. Clin Ter. 1980;95(2):157-164. Italian.
  23. Dehpour AR, et al. Liquorice components protect liver damage induced by actaminophen. Poster Presentation, 48th Annual Meeting of the International Congress of the Society of Medicinal Plant Research, P2A/23. 2000.
  24. Shear NH, Malkiewicz IM, Klein D, et al. Acetaminophen-induced toxicity to human epidermoid cell line A431 and hepatoblastoma cell line hep G2, in vitro, is diminished by silymarin. Skin Pharmacol. 1995;8(6):279-291.
  25. Ferenci P, Scherzer TM, Kerschner H, et al. Silibinin is a potent antiviral agent in patients with chronic hepatitis C not responding to pegylated interferon/ribavirin therapy. Gastroenterology. 2008;135(5):1561-1567.
  26. Gordon A, Hobbs DA, Bowden DS, et al. Effects of Silybum marianum on serum hepatitis C virus RNA, alanine aminotransferase levels and well-being in patients with chronic hepatitis C. J Gastroenterol Hepatol. 2006;21(1 Pt 2):275-280.
  27. Saller R, Brignoli R, Melzer J, Meier R. An updated systematic review with meta-analysis for the clinical evidence of silymarin. Forsch Komplementmed. 2008;15(1):9-20.
  28. Edwards J, Grange LL, Wang M, et al. Fetoprotectivity of the flavanolignan compound siliphos against ethanol-induced toxicity. Phytother Res. 2000;14(7):517-521.
  29. Flora K, Hahn M, Rosen H, Benner K. Milk thistle (Silybum marianum) for the therapy of liver disease. Am J Gastroenterol. 1998;93(2):139-143
  30. Rambaldi A, Jacobs BP, Gluud C. Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases. Cochrane Database Syst Rev. 2007;(4):CD003620.
  31. Kim S, Choi JH, Lim HI, et al. Silibinin prevents TPA-induced MMP-9 expression and VEGF secretion by inactivation of the Raf/MEK/ERK pathway in MCF-7 human breast cancer cells. Phytomedicine. 2009;16(6-7):573-580.
  32. García-Maceira P, Mateo J. Silibinin inhibits hypoxia-inducible factor-1alpha and mTOR/p70S6K/4E-BP1 signaling pathway in human cervical and hepatoma cancer cells: implications for anticancer therapy. Oncogene. 2009;28(3):313-324.
  33. Bang CI, Paik SY, Sun DI, Joo YH, Kim MS. Cell growth inhibition and down-regulation of survivin by silibinin in a laryngeal squamous cell carcinoma cell line. Ann Otol Rhinol Laryngol. 2008;117(10):781-785.
  34. Jung HJ, Park JW, Lee JS, et al. Silibinin inhibits expression of HIF-1alpha through suppression of protein translation in prostate cancer cells. Biochem Biophys Res Commun. 2009;390(1):71-76.
  35. Hogan FS, Krishnegowda NK, Mikhailova M, Kahlenberg MS. Flavonoid, silibinin, inhibits proliferation and promotes cell-cycle arrest of human colon cancer. J Surg Res. 2007;143(1):58-65.
  36. Ramasamy K, Agarwal R. Multitargeted therapy of cancer by silymarin. Cancer Lett. 2008;269(2):352-362.
  37. Greenlee H, Abascal K, Yarnell E, Ladas E. Clinical applications of Silybum marianum in oncology. Integr Cancer Ther. 2007;6(2):158-165.
  38. Sonnenbichler J, Scalera F, Sonnenbichler I, et al. Stimulatory effects of silibinin and silicristin from the milk thistle silybum marianum on kidney cells. J Pharmacol Exp Ther. 1999;290(3):1375-1383.
  39. Hoh C, Boocock D, Marczylo T, et al. Pilot study of oral silibinin, a putative chemopreventive agent, in colorectal cancer patients: silibinin levels in plasma, colorectum, and liver and their pharmacodynamic consequences. Clin Cancer Res. 2006;12(9):2944-2950.
  40. Singh RP, Agarwal R. Cosmeceuticals and silibinin. Clin Dermatol. 2009;27(5):479-484.
  41. Li LH, Wu LJ, Tashiro SI, Onodera S, Uchiumi F, Ikejima T. Activation of the SIRT1 pathway and modulation of the cell cycle were involved in silymarin's protection against UV-induced A375-S2 cell apoptosis. J Asian Nat Prod Res. 2007;9(3-5):245-252.
  42. Li LH, Wu LJ, Tashiro S, Onodera S, Uchiumi F, Ikejima T. Silibinin prevents UV-induced HaCaT cell apoptosis partly through inhibition of caspase-8 pathway. Biol Pharm Bull. 2006;29(6):1096-1101.
  43. Krecman V, Skottova N, Walterova D, Ulrichová J, Simánek V. Silymarin inhibits the development of diet-induced hypercholesterolemia in rats. Planta Med. 1998;64(2):138-142
  44. Skottova N, Krecman V, Walterova D, et al. Effect of silymarin on serum cholesterol levels in rats. Acta Univ Palacki Olomuc Fac Med. 1998;141:87-89.
  45. Skottova N, Krecman V. Silymarin as a potential hypocholesterolaemic drug. Physiol Res. 1998;47(1):1-7.
  46. Di Pierro F, Callegari A, Carotenuto D, Tapia MM. Clinical efficacy, safety and tolerability of BIO-C (micronized Silymarin) as a galactagogue. Acta Biomed. 2008;79(3):205-210.
  47. Wallace S, Vaughn K, Stewart BW, et al. Milk thistle extracts inhibit the oxidation of low-density lipoprotein (LDL) and subsequent scavenger receptor-dependent monocyte adhesion. J Agric Food Chem. 2008;56(11):3966-3972.
  48. David R. Integrative medicine. Netherlands: Elsevier, 2007; p. 494
  49. LaValle JB, Krinsky D, Hawkins EB, et al. Natural therapeutics pocket guide. Hudson, Ohio: LexiComp Inc, 2000; p. 479-480.
  50. Wu JW, Lin LC, Tsai TH. Drug-drug interactions of silymarin on the perspective of pharmacokinetics. J Ethnopharmacol. 2009;121(2):185-193.