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.
Return to Plant Summaries page
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.