Milk thistle

Chinese Name: Shui fei ji
Medical Name:
Latin Name: Silybum marianum
Taste: Mild

Quotes from Chinese historical sources

A DICTIONARY OF CHINESE HERBS: Milk thistle is used to dislodge toxins from the liver, and to protect the muscles of the heart from toxic damage.

Western Research

RESEARCHER'S NOTE: Silymarin, the active component of milk thistle sap, is included in the pharmacopoeia of many countries under the trademark LegalonTM or HepatronTM and is often used as supportive therapy in food poisoning due to fungi and in chronic liver disorders.

J Dermatol Sci. 2007 Feb 6
Attenuation of UVA-induced damage to human keratinocytes by silymarin.
Svobodova A, Zdarilova A, Maliskova J, Mikulkova H, Walterova D, Vostalova J.
Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacky University, Hnevotinska 3, 775 15 Olomouc, Czech Republic.
BACKGROUND: UV radiation from sunlight is a potent environmental risk factor in skin cancer pathogenesis. UVA is the major portion of UV light reaching the earth surface ( approximately 95%) and it is reported to lead to benign and malignant tumor formation. UVA-mediated cellular damage occurs primarily through the release of reactive oxygen species (ROS) and it is responsible for inflammation, immunosuppression, photoaging and photocarcinogenesis. OBJECTIVE: The aim of our study was to investigate the potency of silymarin, the polyphenol fraction from the seeds of Silybum marianum, to modulate UVA-induced oxidative damage to human keratinocytes. METHODS: Skin epidermal cell line HaCaT, extensively used for studying the influence of UV radiation, was chosen as an experimental model. Silymarin's effect on UVA-disrupted cell viability, proliferation, mitochondrial function, and intracellular ATP and GSH level was measured. Furthermore, silymarin's potency to reduce UVA-induced ROS generation, membrane lipid peroxidation, caspase-3 activation and DNA damage was monitored. RESULTS: Treatment of irradiated HaCaT (20J/cm(2)) with silymarin (0.7-34mg/l; 4h) resulted in concentration-dependent diminution of UVA-caused oxidative stress on all studied parameters. Silymarin application extensively reduced GSH depletion and ROS production as well as lipid peroxidation in irradiated cells. Formation of UVA-induced DNA single strand breaks and caspase-3 activity was also significantly decreased by silymarin. CONCLUSION: The results suggest that silymarin may be beneficial in the treatment of UVA-induced skin oxidative injury and inflammation. However, further studies especially whose using human systems are needed to determine efficacy of silymarin in vivo.

Anticancer Res. 2006 Nov-Dec;26(6B):4457-98.
Anticancer potential of silymarin: from bench to bed side.
Agarwal R, Agarwal C, Ichikawa H, Singh RP, Aggarwal BB.
Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
Silymarin consists of a family of flavonoids (silybin, isosilybin, silychristin, silydianin and taxifoline) commonly found in the dried fruit of the milk thistle plant Silybum marianum. Although silymarin's role as an antioxidant and hepatoprotective agent is well known, its role as an anticancer agent has begun to emerge. Extensive research within the last decade has shown that silymarin can suppress the proliferation of a variety of tumor cells (e.g., prostate, breast, ovary, colon, lung, bladder); this is accomplished through cell cycle arrest at the G1/S-phase, induction of cyclin-dependent kinase inhibitors (such as p15, p21 and p27), down-regulation of anti-apoptotic gene products (e.g., Bcl-2 and Bcl-xL), inhibition of cell-survival kinases (AKT, PKC and MAPK) and inhibition of inflammatory transcription factors (e.g., NF-kappaB). Silymarin can also down-regulate gene products involved in the proliferation of tumor cells (cyclin D1, EGFR, COX-2, TGF-beta, IGF-IR), invasion (MMP-9), angiogenesis (VEGF) and metastasis (adhesion molecules). The antiinflammatory effects of silymarin are mediated through suppression of NF-kappaB-regulated gene products, including COX-2, LOX, inducible iNOS, TNF and IL-1. 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 (DMBA), phorbol 12-myristate 13-acetate (PMA) and others. Silymarin has also been shown to sensitize tumors to chemotherapeutic agents through down-regulation of the MDR protein and other mechanisms. It binds to both estrogen and androgen receptors, and down-regulates PSA. In addition to its chemopreventive effects, silymarin exhibits antitumor activity against human tumors (e.g., prostate and ovary) in rodents. Various clinical trials have indicated that silymarin is bioavailable and pharmacologically safe. Studies are now in progress to demonstrate the clinical efficacy of silymarin against various cancers.

Phytother Res. 2006 Dec;20(12):1036-9.
The efficacy of Silybum marianum (L.) Gaertn. (silymarin) in the treatment of type II diabetes: a randomized, double-blind, placebo-controlled, clinical trial.
Huseini HF, Larijani B, Heshmat R, Fakhrzadeh H, Radjabipour B, Toliat T, Raza M.
Department of Pharmacology, Institute of Medicinal Plants, ACECR Tehran, Iran.
Oxidative stresses are increasingly implicated in the pathogenesis of diabetic complications which may either cause direct pancreatic beta-cell damage or lead to metabolic abnormalities that can induce or aggravate diabetes. The valuable effect of antioxidant nutrients on the glycemic control of diabetic patients has been reported in experimental and clinical studies. The present study was designed to investigate the effects of the herbal medicine, Silybum marianum seed extract (silymarin), which is known to have antioxidant properties on the glycemic profile in diabetic patients. A 4-month randomized double-blind clinical trial was conducted in 51 type II diabetic patients in two well-matched groups. The first group (n = 25) received a silymarin (200 mg) tablet 3 times a day plus conventional therapy. The second group (n = 26) received the same therapy but a placebo tablet instead of silymarin. The patients were visited monthly and glycosylated hemoglobin (HbA(1)c), fasting blood glucose (FBS), insulin, total cholesterol, LDL and HDL, triglyceride, SGOT and SGPT levels were determined at the beginning and the end of the study. The results showed a significant decrease in HbA(1)c, FBS, total cholesterol, LDL, triglyceride SGOT and SGPT levels in silymarin treated patients compared with placebo as well as with values at the beginning of the study in each group. In conclusion, silymarin treatment in type II diabetic patients for 4 months has a beneficial effect on improving the glycemic profile.

Clinical Drug Investigation, Volume 22, Number 1, 2002, pp. 51-65(15)
Pharmacology of Silymarin
F. Fraschini, G. Demartini, D. Esposti
Silymarin is a well tolerated and effective antidote for use in hepatotoxicity produced by a number of toxins, including A. phalloides, ethanol and psychotropic drugs. Numerous experimental studies suggest that it acts as a free radical scavenger, with other liver-specific properties that make it a unique hepatoprotective agent.

Med Sci Monit 2002 Nov;8(11):BR439-43
Immunostimulatory effect of Silybum Marianum (milk thistle) extract.
Wilasrusmee C, Kittur S, Shah G, Siddiqui J, Bruch D, Wilasrusmee S, Kittur DS.
The Johns Hopkins University School of Medicine, Department of Surgery SUNY Upstate Medical University.
We investigated the effects of Milk Thistle on the immune system. Our study has uncovered a novel effect of milk thistle on the immune system. This immunostimulatory effect may be of benefit in increasing the immunity to infectious diseases.
Int J Oncol 2002 Dec;21(6):1213-22

Clin Cancer Res 2002 Nov;8(11):3512-9
Silibinin strongly synergizes human prostate carcinoma DU145 cells to doxorubicin-induced growth Inhibition, G2-M arrest, and apoptosis.
Tyagi AK, Singh RP, Agarwal C, Chan DC, Agarwal R.
Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
Silibinin and doxorubicin alone as well as in combination were effective in inhibiting the growth of androgen-dependent prostate carcinoma LNCaP cells. These findings suggest a need for in vivo studies with this combination in preclinical prostate cancer models.

Am J Med 2002 Oct 15;113(6):506-15
Milk thistle for the treatment of liver disease: a systematic review and meta-analysis.
Jacobs BP, Dennehy C, Ramirez G, Sapp J, Lawrence VA.
Department of Medicine, University of California, San Francisco 94143, USA.
Treatment with milk thistle appears to be safe and well tolerated. We 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.

Drugs 2001;61(14):2035-63
The use of silymarin in the treatment of liver diseases.
Saller R, Meier R, Brignoli R.
Abteilung Naturheilkunde, University Hospital Zurich, Switzerland.
Available evidence suggests that silymarin may play a role in the therapy of (alcoholic) liver cirrhosis. Silymarin is has a good safety record and only rare case reports of gastrointestinal disturbances and allergic skin rashes have been published. This review does not aim to replace future prospective trials aiming to provide the 'final' evidence of the efficacy of silymarin.

Cancer Res 2000 Oct 15;60(20):5617-20
Silibinin up-regulates insulin-like growth factor-binding protein 3 expression and inhibits proliferation of androgen-independent prostate cancer cells.
Zi X, Zhang J, Agarwal R, Pollak M.
Lady Davis Research Institute of Jewish General Hospital and Department of Oncology, McGill University, Montreal, Quebec, Canada.
Silibinin, a naturally occurring flavonoid antioxidant found in the milk thistle, has recently been shown to have potent antiproliferative effects against various malignant cell lines. The results suggest a novel mechanism by which silibinin acts as an antiproliferative agent and justify further work to investigate potential use of this compound or its derivatives in prostate cancer treatment and prevention.

Drug Metab Dispos 2000 Nov;28(11):1270-3
Milk thistle, a herbal supplement, decreases the activity of CYP3A4 and uridine diphosphoglucuronosyl transferase in human hepatocyte cultures.
Venkataramanan R, Ramachandran V, Komoroski BJ, Zhang S, Schiff PL, Strom SC.
Department of Pharmaceutical Sciences School of Pharmacy, Pennsylvania, USA.
The observations point to the potential of silymarin to impair hepatic metabolism of certain coadministered drugs in humans. Indiscriminate use of herbal products may lead to altered pharmacokinetics of certain drugs and may result in increased toxicity of certain drugs.

Cancer Lett 1999 Dec 1;147(1-2):77-84
Inhibition of human carcinoma cell growth and DNA synthesis by silibinin, an active constituent of milk thistle: comparison with silymarin.
Bhatia N, Zhao J, Wolf DM, Agarwal R.
Center for Cancer Causation and Prevention, AMC Cancer Research Center, Denver, CO 80214, USA.
Treatment of different prostate, breast, and cervical human carcinoma cells with silibinin resulted in a highly significant inhibition of both cell growth and DNA synthesis in a time-dependent manner with large loss of cell viability only in case of cervical carcinoma cells. Based on the comparable results of silibinin and silymarin, we suggest that the cancer chemopreventive and anti-carcinogenic effects of silymarin reported earlier are due to the main constituent silibinin.

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

Proc Natl Acad Sci U S A 1999 Jun 22;96(13):7490-5
Silibinin decreases prostate-specific antigen with cell growth inhibition via G1 arrest, leading to differentiation of prostate carcinoma cells: implications for prostate cancer intervention.
Zi X, Agarwal R.
Center for Cancer Causation and Prevention, AMC Cancer Research Center, 1600 Pierce Street, Denver, CO 80214, USA.
Silibinin treatment of cells grown in serum resulted in a significant decrease in both intracellular and secreted forms of PSA concomitant with a highly significant to complete inhibition of cell growth. These results suggest that silibinin could be a useful agent for the intervention of hormone-refractory human prostate cancer.

Cancer Res 1998 May 1;58(9):1920-9
A flavonoid antioxidant, silymarin, inhibits activation of erbB1 signaling and induces cyclin-dependent kinase inhibitors, G1 arrest, and anticarcinogenic effects in human prostate carcinoma DU145 cells.
Zi X, Grasso AW, Kung HJ, Agarwal R.
Department of Dermatology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Silymarin, a flavonoid antioxidant isolated from milk thistle, possesses exceptionally high to complete protective effects against experimentally induced tumorigenesis. Silymarin may exert a strong anticarcinogenic effect against PCA.

Clin Cancer Res 1998 Apr;4(4):1055-64
Anticarcinogenic effect of a flavonoid antioxidant, silymarin, in human breast cancer cells MDA-MB 468: induction of G1 arrest through an increase in Cip1/p21 concomitant with a decrease in kinase activity of cyclin-dependent kinases and associated cyclins.
Zi X, Feyes DK, Agarwal R.
Department of Dermatology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Silymarin may exert a strong anticarcinogenic effect against breast cancer and this effect possibly involves an induction of Cip1/p21 by silymarin, which inhibits the threshold kinase activities of CDKs and associated cyclins, leading to a G1 arrest in cell cycle progression.

Cell Mol Life Sci 1997 Dec;53(11-12):917-20
Silibinin, a plant extract with antioxidant and membrane stabilizing properties, protects exocrine pancreas from cyclosporin A toxicity.
von Schonfeld J, Weisbrod B, Muller MK.
Department of Gastroenterology, Medical Clinic, Essen, Germany.
Silymarin and silibinin have been shown to protect different organs and cells against a number of insults. Thus silibinin inhibits glucose-stimulated insulin release in vitro, while not affecting blood glucose concentration in vivo. Furthermore, silibinin protects the exocrine pancreas from CiA toxicity. Silibinin may also protect the exocrine pancreas against other insult principles, such as alcohol.

Methods Find Exp Clin Pharmacol 1985 Aug;7(8):409-13
Silymarin: potent inhibitor of cyclic AMP phosphodiesterase.
Koch HP, Bachner J, Loffler E.
Silymarin is a very potent inhibitor of cyclic AMP breakdown in vitro by a commercial beef heart phosphodiesterase preparation. Its main constituents, 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 in this respect.