Medical Attributes of Silybum marianum - milk thistle

By Amanda Gryskewicz, Amy Sieklicki, and Stefanie Macri
Wilkes University, Wilkes-Barre, PA

July, 2007
Silybum marianum, commonly called milk thistle, is a flowering plant belonging to the Asteraceae (Aster family).  S. marianum has a branching stem that can reach 4 to 10 feet in height.  Its flowers are large and disc-shaped, while the leaves are alternate, wide, toothed and spiny (Wikipedia 2007).  Milk thistle is native to the Mediterranean regions of Europe, North Africa and the Middle East, although it is now known as a species in the United States, mostly in southeastern states.

This plant has been used since Greco-Roman times as an herbal remedy for a variety of ailments (UMMC 2002). The written history of S. marianum is unclear; however the most common historical uses are treatment for congestion of the liver, spleen and kidneys, chronic hepatitis, and cirrhosis associated with alcohol (Ackerson 2005).

The active ingredients in S. marianum are considered to be silymarin and silibinin. Silymarin is a complex of seven flavonolignans and polyphenols; although silibinin is usually regarded as the most active component.

In vitro and in vivo studies have shown that both compounds protect the liver from oxidative stress and sustained inflammatory processes. The prevention of oxidative stress and inflammation by these compounds also protects against other cellular damage of many other tissues. The protective roles that both silymarin and silibinin demonstrate suggest clinical applications in cancer patients as an adjunct to the established therapies of the liver (Comelli, et. al. 2007).

Currently S. marianum is still thought to have some positive effects in treating diseases of the liver. Not only has it been shown that silymarin protects the liver from damage due to toxins, viruses, alcohol, and certain drugs such as acetaminophen (UMMC 2006), but it has also been shown that silymarin boosts the regeneration of damaged liver tissue (Pradhan & Girish 2006).  

    Many herbalists recommend the use of milk thistle to treat liver disorders resulting from long term use of alcohol. Saller, et. al. (2001) found that silymarin may play a role in the therapy of (alcoholic) liver cirrhosis.  In two out of two trials, patients with alcoholic liver disease that were treated with silymarin experienced an improvement in prothrombin time, and liver transaminase levels were significantly lower in the silymarin-treated groups (Saller, et.al. 2001).  As a result, this study suggests that silymarin may be useful as a chemical catalyst in the therapy of alcoholic liver disease. 

    The effects of silymarin on hepatotoxicity and hepatobiliary diseases were examined by Pradhan & Girish (2006).  They concluded that silymarin might prove to be useful for protecting the liver against these harmful ailments.  But when it comes to treating viruses such as hepatitis Torres, et. al. (2004) found that milk thistle does not work as an antiviral agent, though it does have a protective effect against inflammation caused by the virus. 

    S. marianum extracts are known to be safe and well tolerated (Tamayo & Diamond 2007).  Only a few reactions were noted throughout all of the studies, including: gastrointestinal problems, headache, neuropsychological events, arthralgia, rhinoconjunctivitis, impotence, anaphylaxis, and skin rashes (AHRQ 2000; UMMC 2006).  Many of these reactions could be dose dependent, or due to the preparation of the herb.  

    In recent years, it has been shown that both silymarin and silibinin are also useful in treating several types of cancer, including cancers of the prostate, breast, ovaries, colon, lung, skin, and bladder (Agarwal, et. al. 2006). The extracts of milk thistle are currently under intense study in the experimental therapeutics of chemoprevention, treatment, and amelioration of chemotherapy side effects (Kroll, et. al. 2007).

    Silymarin is the specific extract from S. marianum that has undergone most of the extensive research within the last decade for its medicinal value in treating cancer. Its mixture of polyphenolic flavenoids have been proven to have some anticancer activities by suppressing the proliferation of tumor cells.(Malewicz, et. al. 2006; Agarwal, et. al. 2006). This is accomplished by the ability of silymarin to arrest the cell cycle at the G1/S-phase, and the induction of cyclin-dependent kinase inhibitors, such as p14, p21, and p27. In addition, silymarin also has been shown to down-regulate anti-apoptotic gene products, such as Bcl-2 and Bcl-xL, and inhibit inflammatory transcription factors, such as NF-kappaB (Agarwal, et. al. 2006).

    The therapeutic role of silymarin against cancer is shown to be especially effective against skin and prostate cancer sites. In skin cancer, silymarin treatment inhibits chemically initiated or promoted carcinogenesis. These effects are attributed to silymarin’s ability to prevent UVB-induced immuno-suppression and oxidative stress (Kativar 2002). In prostate cancer, silymarin treatment down-regulates androgen receptor-, epidermal growth factor receptor-, and nuclear factor-kappaB-mediated signaling and induces cell cycle arrest. (Deep & Agarwal 2007).

    Although few studies have evaluated its use alongside conventional cytotoxic therapies, the drug-interaction potential of the extracts appears to be quite low. In fact, silibinin, another extract from S. marianum, appears to synergize with the antitumor effects of some commonly used chemotherapeutics. Adverse events associated with long-term administration are still uncertain (Sagar 2007; Saller, et. al. 2007).

    Although S. marianum still proves controversial in treating diseases of the liver, it has recently been shown to be effective in treating cancers of several organ systems. (Saller et. al. 2001).  Future studies based on the role that S. marianum plays on the liver should include high-quality randomized clinical trials on milk thistle versus placebo in order to determine the safety and effectiveness of this herb (Tamayo & Diamond 2007). 

    Possible future oncology indications include cleansing and detoxification after chemotherapy, preventing hepatotoxicity during chemotherapy, preventing the potentiation of chemotherapy and radiation therapy as an adjunctive treatment (Greenlee, et. al. 2007). Future oncology research should focus on authentication of active chemicals, pharmacokinetics, adverse interactions and quality control, prevention of cancer initiation and progression, adjuvant therapy for specific cancers, and prevention of toxicity from anticancer therapies (Sager 2007).

    Milk thistle has been used as an herbal remedy for centuries, although the medicinal value has just recently been explored. Thus far, the positive effects are far greater in number than the negatives, especially in regard to cancer therapy. If additional trials also prove favorable, S. marianum extracts may be in mainstream use for treatment of liver diseases as well as cancer.

LITERATURE CITED

Ackerson, A.  2005.  Milk Thistle.  Better Nutrition. http://findarticles.com/p/articles/mi_m0FKA/Is_1_67/ai_n8582801. Accessed 12 Jun 2007

Agarwal, R., C. Agarwal, H. Ichikawa, R.P. Singh, & B.B. Agarwal.  2006.  Anticancer potential of silymarin: from bench to bedside. Anticancer Res. 26(6B): 4457-4498.

Anonymous.  April 2002.  Milk Thistle.  University of Maryland Medical Center, Baltimore, MD.     http://www.umm.edu/altmed/articles/milk-thistle-000266.htm.  Accessed 12 Jun 2007

Anonymous.  Milk thistle. Wikipedia, The Free Encyclopedia.  Wikimedia
Foundation, Inc. http://en.wikipedia.org/w/index.php?title=Milk_thistle&oldid=137637776.  Accessed 12 Jun 2007

Anonymous.  September 2000.  Milk Thistle: Effects on Liver Disease and Cirrhosis and Clinical Adverse Effects.  Summary, Evidence Report/Technology Assessment: Number 21. Agency for Healthcare Research and Quality, Rockville, MD.  http://www.ahrq.gov/clinic/epcsums/milktsum.htm. Accessed 12 Jun 2007

Comelli, M.C., U. Mengs, C. Schneider, & M. Prosdocimi.  2007.  Toward the definition of the mechanism of action of silymarin: activities related to cellular protection from toxic damage induced by chemotherapy. Integer Cancer Ther 6(2): 120-129.

Deep, G. & R. Agarwal.  2007.  Chemopreventive efficacy of silymarin in skin and prostate cancer. Integer Cancer Ther. 6(2):130-145.

Greenlee, H., K. Abascal, E. Yarnell, & E. Ladas.  2007.  Clinical applications of Silybum marianum in oncology. Integer Cancer Ther 6(2):158-165.

Kativar, S.K.  2002.  Treatment of silymarin, a plant flavonoid, prevents ultraviolet light-induced immune suppression and oxidative stress in mouse skin. Int J Oncol 21(6):1213-1222.
    
Kroll, D.J., H.S. Shaw, & N.H. Oberlies.  2007.  Milk thistle nomenclature: why it matters in cancer research and pharmacokinetic studies. Integr Cancer Ther 6(2):110-119.

Malewicz, B., Z. Wang, C. Jiang, J. Guo, M.P. Cleary, J.P. Grande, & J. Lu.  2006.  Enhancement of mammary carcinogenesis in two rodents models by silymarin dietary supplements. Carcinogenesis 27(9):1739-1747.

Pradhan, S.C. & C. Girish.  2006.  Hepatoprotective herbal drug, silymarin from experimental pharmacology to clinical medicine.  Indian J Med Res  124(5): 491-504.  

Sagar, S.M.  2007.  Future directions for research on Silybum marianum for cancer patients. Integr Cancer Ther 6(2): 166-173.

Saller R., J. Meizer, J. Reichling, R. Brignoli, & R. Meier. 2007.  An updated systematic review of the pharmacology of silymarin. Forsch Komplementarmed 14(2): 70-80.

Saller, R., R. Meier, & R. Brignoli.  2001.  The use of silymarin in the treatment of liver diseases. Drugs  61(41): 2035-63.  

Tamayo C. & S. Diamond.  2007.  Review of clinical trials evaluating safety and efficacy of milk thistle (Silybum marianum [l.] Gaertn.).  Integr Cancer Ther  6(2): 146-57.

Torres, M., F. Rodriguez-Serrano, D.J. Rosario, F. Rodriguez-Perez, & D.H. Toro.  2004.  Does Silybum marianum play a role in the treatment of chronic hepatitis C?  P R Health Sci J  23(2 Suppl): 69-74.  


This paper was developed as part of the BIO 368 - Medical Botany course offered at Wilkes University during the summer of 2007. Course instructor was Kenneth M. Klemow, Ph.D. (kklemow@wilkes.edu). The information contained herein is based on published sources, and is made available for academic purposes only. No warrantees, expressed or implied, are made about the medical usefulness or dangers associated with the plant species in question.

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This page posted and maintained by Kenneth M. Klemow, Ph.D., Biology Department, Wilkes University, Wilkes-Barre, PA 18766. (570) 408-4758, kklemow@wilkes.edu.