210

Current Pharmaceutical Biotechnology, 2012, 13, 210-217

Silymarin in the Prevention and Treatment of Liver Diseases and Primary

Liver Cancer
Jnos Fehr and Gabriella Lengyel*
2nd Department of Medicine, Semmelweis University, Budapest, Hungary
Abstract: In chronic liver diseases caused by oxidative stress (alcoholic and non-alcoholic fatty liver diseases, drug- and
chemical-induced hepatic toxicity), the antioxidant medicines such as silymarin can have beneficial effect. Liver cirrhosis,
non-alcoholic fatty liver and steatohepatitis are risk factors for hepatocellular carcinoma (HCC). Insulin resistance and
oxidative stress are the major pathogenetic mechanisms leading the hepatic cell injury in these patients. The silymarin exerts membrane-stabilizing and antioxidant activity, it promotes hepatocyte regeneration; furthermore it reduces the inflammatory reaction, and inhibits the fibrogenesis in the liver. These results have been established by experimental and
clinical trials. According to open studies the long-term administration of silymarin significantly increased survival time of
patients with alcohol induced liver cirrhosis. Based on the results of studies using methods of molecular biology, silymarin can significantly reduce tumor cell proliferation, angiogenesis as well as insulin resistance. Furthermore, it exerts an
anti-atherosclerotic effect, and suppresses tumor necrosis factor-alpha-induced protein production and mRNA expression
due to adhesion molecules. The chemopreventive effect of silymarin on HCC has been established in several studies using
in vitro and in vivo methods; it can exert a beneficial effect on the balance of cell survival and apoptosis by interfering cytokines. In addition to this, anti-inflammatory activity and inhibitory effect of silymarin on the development of metastases
have also been detected. In some neoplastic diseases silymarin can be administered as adjuvant therapy as well.

Keywords: Cancer prevention, chronic liver diseases, hepatitis B virus, hepatitis C virus, hepatocellular carcinoma, silymarin,
steatohepatitis.
INTRODUCTION
Silymarin is an extract of the milk thistle (Silybum marianum). The tea made of milk thistle was used for the treatment of liver diseases already in the ancient world. Dating
back to the time of the ancient Greeks (Theophrastus, 4th
century B.C.) and Romans (Pliny the Elder, 1st century
A.D.), the seeds of milk thistle (also known as St. Marys
thistle and ladys thistle), have been used to protect liver
health [1]. In the 1st century A.D., Dioskurides used this
plant as an emetic as well as a general medicinal herb. It
became a favored medicine for hepatobiliary diseases in 16th
century and the drug was revived again in 1960 in central
Europe [2,3]. Milk thistle grows up to 6 feet tall, particularly
well on sunny slopes in Mediterranean countries, particularly
Spain and Greece. The plant of the milk thistle blooms from
June through August, and the shiny black seeds are harvested
after the end of the summer to be used for medicinal purposes [1].
Silymarin is a mixture of flavonoids and polyphenols.
The commercial silymarin preparations contain several different flavonoids, like silibinin (silybin A and B), isosilibinin
(isosilybin A and B), silichristin and silidianin Fig. (1).
Silibinin is the major bioactive component of this material.
The most prevalent forms are the diastereoisomers silybin A
and silybin B. Silymarin has membrane-stabilizing and
*Address correspondence to this author at the 2nd Department of Medicine,
Semmelweis University, H-1088 Budapest, Szentkirlyi str. 46, Hungary;
Tel: +3630 984 6953; Fax: +361 317 4548; E-mail: lengyel@bel2.sote.hu

Dedicated to the memory of Professor Jnos Fehr (1932-2010).

1389-2010/12 $58.00+.00

antioxidant activity, it promotes hepatocyte regeneration,

reduces inflammatory reaction, and inhibits fibrogenesis.
These results have been established in experimental and
clinical trials [4-13].
The pharmacological data [1, 14] show that silymarin
possesses fairly specific effects on cell-regulating mechanisms, beyond the well known reactive oxygen species
(ROS) scavenging properties confirmed in new studies, indicating a potential to reduce toxic effects of other drugs (e.g.
cisplatin, amiodarone). This scavenging effect has been
proved by atomic force microscopic examinations [15]. In
some models, silymarin already at low dose was shown to
reduce the inducible nitric oxide synthase-mediated production of nitric oxide and to modulate the inflammatory immune response [1, 14].
In liver diseases caused by oxidative stress (alcoholic and
non-alcoholic fatty liver and steatohepatitis, drug- and
chemically-induced hepatic toxicity) the antioxidant medicines such as silymarin is the primary therapeutic modality
of choice [4, 16, 17]. This can be realized in part by proper
composition of food, in part by application of free radical
scavengers such as the marketed silymarin products [18-21].
Recently several reports have dealt with the beneficial effect
of silymarin not only in chronic liver diseases caused by oxidative stress, but also in viral-induced chronic hepatitis and
in primary liver cancer. Chronic hepatitis and liver cirrhosis
are the risk factors of hepatocellular carcinoma (HCC). In
several studies the chemopreventive and adjuvant effect of
silymarin has been also established in different kind of tumors.
2012 Bentham Science Publishers

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Current Pharmaceutical Biotechnology, 2012, Vol. 13, No. 1

211

OH

Silibinin

O
2'

CH2OH

3'

HO

HO

OH

CH2OH

OCH3

OCH3
OH

OCH3

Silidianin

OH
O

OH

Silichristin
HO

OCH3
OH

OH
OH

Isosilibinin

H
H
O

CH2OH

OH

OH
OH

Fig. (1). Molecules of the components of silymarin.

SILYMARIN AND LIVER DISEASES

Silymarin and Experimental Liver Damage
Hepatoprotective activity of silymarin has been demonstrated by various researchers from all over the world against
partial hepatectomy models and toxic models in experimental animals by using acetaminophen [22], carbon tetrachloride [23, 24], ethanol, D-galactosamine and Amanita phalloides toxin [25]. Silymarin has also been found to protect
liver cells from injury caused by ischemia, radiation and viral hepatitis [25]. In these experiments the biochemical
markers of hepatocyte damage namely, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and glutamyl transpeptidase, caused by the toxic effects were
decreased. The signs of lipid peroxidation (malondialdehyde
content) and the parameters of antioxidant capacity (activities of superoxide dismutase, catalase, and glutathione peroxidase) beneficially changed after silymarin treatment [2527]. Additional demonstrations of silimaryn effects include
up regulation of low-density lipoprotein receptor and peroxisome proliferators-activated alpha gene expression [27].
Newer novel findings suggest that silymarin and garlic have
a synergistic effect, and could be used as hepatoprotective
agents [28].
Silymarin and Micronodular Liver Cirrhosis
In our own earlier clinical pharmacological studies [7, 11,
12] we have demonstrated in a prospective multicentre controlled trial, treatment with silymarin (Legalon 140, Madaus,
Cologne, Germany) for 6 months in 36 human patients (biopsy confirmed) with micronodular hepatic cirrhosis (Child
A). The treatment had a beneficial effect on immune response of the body and on parameters of the antioxidant protective mechanism [11, 12]. Serum procollagen III levels
also decreased significantly in the therapeutic group during
the 6 months of treatment, indicating inhibition of fibrogenesis in the hepatic tissue [7]. Our open studies similarly to the
data of Ferenci et al. [4] showed that the long-term administration of silymarin significantly increased the life expec-

tancy of patients with alcohol induced liver cirrhosis in a

period by 5-10 years [17].
Silymarin and Non-Alcoholic Fatty Liver Diseases
Non-alcoholic fatty liver disease (NAFLD) is a multifactorial liver injury, one form a significant risk for HCC. It
includes a wide spectrum of liver damage characterized by
histological changes of alcoholic origin (ranging from uncomplicated fatty liver to steatohepatitis, fibrosis and cirrhosis) in non-alcoholics (< 20 g/day ethanol consumption). It is
developed mainly by insulin resistance and oxidative stress,
but the exact metabolic and cellular mechanisms are not fully
understood [29-31].
Researches have identified the factors that can play a
causative role: oxidative stress, abnormal cytokine production, fatty-acid metabolic disturbance and insulin resistance.
The combination of these events causes hepatocyte injury via
direct oxidative injury, tumor necrosis factor-alpha (TNF-
)
induced apoptosis, or inflammation [29-35]. This disease is a
two hit alteration in the liver: first phase is the pure steatosis
and the second phase is characterized by steatohepatitis
(non-alcoholic steatohepatitis, NASH) or fatty liver cirrhosis.
Currently, treatment of NAFLD is focused on modifying risk
factors (obesity, diabetes mellitus, and hyperlipidemia).
Many therapeutic approaches have been attempted with
varying degrees of success [36, 37].
Mitochondrial dysfunction and oxidative stress are determinant events in the pathogenesis of NASH. Silymarin
has been shown to have antioxidant, anti-inflammatory, and
antifibrotic effects in chronic liver disease. In several experimental models [38-40] and in clinical trial [31, 41-44]
different authors have demonstrated the beneficial effect of
silymarin silibinin, silybin-phospholipid complex, silybinvitamin E-phospholipids complex. These therapy modalities
were effective in preventing severe oxidative stress and preserving hepatic mitochondrial bioenergetics in NASH induced in different animal models or in human disease. The
modifications of mitochondrial membrane fatty acid compo-

212 Current Pharmaceutical Biotechnology, 2012, Vol. 13, No. 1

sition induced by methionine- and choline-deficient diet are

partially prevented by silybin-phospholipid complex, conferring anti-inflammatory and antifibrotic effects. The increased
vulnerability of lipid membranes to oxidative damage is limited by silybin-phospholipid complex through preserved mitochondrial function [40].
Silymarin and Hepatitis C Virus Infection
Silymarin inhibits hepatitis C virus (HCV) by displaying
antioxidant, anti-inflammatory, and immunomodulatory actions that contribute to its hepatoprotective effects. Polyak et
al. [45] evaluated the in vitro hepatoprotective actions of the
seven major flavonolignans and one flavonoid that comprise
silymarin. Activities tested included inhibition of HCV cell
culture infection, NS5B polymerase activity, TNF-
-induced
nuclear factot-kappaB (NF-
B) transcription, virus-induced
oxidative stress, and T-cell proliferation. Silymarin suppressed TNF-
activation of NF-B dependent transcription,
which involved partial inhibition of inhibitory B and RelA/
p65 serine phosphorylation, and p50 and p65 nuclear translocation, without affecting the binding of p50 and p65 to
DNA. Flavonolignans blocked JFH-1 virus-induced oxidative
stress, including compounds that lacked antiviral activity.
There are several clinical studies on the use of herbal
extracts, especially silymarin, for the treatment of patients
with chronic hepatitis C, primarily in the belief that this drug
improves response to antiviral agents and reduces adverse
reactions [21, 46-54]. In a recent multicentre trial (HALT-C)
the efficacy of a silymarin preparation added to pegylated
interferon and ribavirin was also studied. The trial included a
total of 1,145 individuals. In 10 centers there were also patients whose treatment was completed with silymarin as well.
Although patients ALT levels and viral load showed no
significant change as compared to those treated with pegylated interferon and ribavirin, the quality of life in patients
receiving silymarin was better as they reported much less
complaints relating to liver disease [55]. Recent studies revealed that silymarin reduces insulin resistance [56]. This
effect has a major impact on chronic hepatitis caused by
HCV because the rate of sustained virological response
(SVR) to the combined treatment with pegylated interferon
and ribavirin in patients with insulin resistance was only a
half (25-33%) as compared to that in patients with no insulin
resistance (60%). Based on the available references of literature a clearly higher rate of SVR can be attained by reducing
insulin resistance prior to the initiation of treatment with
pegylated interferon and ribavirin [57]. At the European Association for the Study of Liver (EASL, 2008) congress in
Milan, Italy, Ferenci et al. [58] presented their most recent
results which showed that silibinin infusion (10 mg/kg Legalon Sil; Madaus, Cologne, Germany), administered for 8
days in patients with chronic hepatitis caused by HCV, significantly (P<0.001) reduced HCV viral load, and thus it
increased the efficacy of pegylated interferon plus ribavirin
therapy and reduced ALT levels as well [58, 59]. The
authors believe that silibinin, as it can be tolerated well also
at high doses, can be helpful in the future when used in combination with up-to-date antiviral therapy in the treatment of
patients with chronic HCV hepatitis not responding to pegylated interferon and ribavirin [59]. Pr et al. [60] confirmed
the beneficial results of silymarin in HCV chronic hepatitis.

Fehr and Lengyel

The nonresponse to combined peginterferon and ribavirin

treatment in infection caused by genotype 1 is associated
with the waist circumference, body mass index (BMI), diabetes, steatosis, and degree of fibrosis. We have published a
history of a 59 years old obese (BMI = 46.47 kg/m2) male
patient with chronic HCV infection. The weight reduction after two ineffective antiviral treatments - helped the biochemical and virological response to combined peginterferon-alpha-2a and ribavirin treatment. Between the combined peginterferon and ribavirin therapy, the patient was
treated with silymarin. Body-weight reduction and silymarin
might have increased the effectiveness of combined peginterferon and ribavirin treatment and thus the sustained virological response in this patient [61]. A new silybin-vitamin Ephospholipid complex can improve the insulin resistance and
liver damage in patients with non-alcoholic fatty liver disease and HCV virus infection [44].
Silymarin and Hepatitis B Virus Infection
Hepatitis B virus (HBV) infection is one of the most important etiologic factors of HCC. Previous studies have revealed that HBV infection is associated with an increased
production of ROS within the liver and that this is responsible for the oxidation of intracellular molecules and activation
of genes related to oxidative stress. In addition, induction of
HBV replication in human hepatoma HepAD38 cells, in
which HBV production is under the control of a tetracyclineregulated promoter, led to up-regulation of genes related to
oxidative stress [62]. According to the study of Wu et al.
[63] the real-time quantitative RT-PCR analysis revealed that
the molecular mechanism of silymarin-mediated antioxidative effect may involve genes related directly or indirectly to
glutathione (GSH) metabolism. Up-regulation of Idh2 facilitates the generation of NADPH and conversion of GSH from
its oxidized to its reduced form. The increase in reduced
GSH further facilitates the removal of H2O2 from cells. In
addition, up-regulation of several glutathione S-transferases
(Gstt2, Gsto1, Gstk1, and Mgst3), whose functions are involved in the conjugation reaction of GSH to diverse electrophilic substrates, reveals the presence of a higher concentration of GSH. Furthermore, genes upregulated by silymarin
and involved in the glutamate metabolism, urea cycle, and
citrate cycle may all indirectly contribute to the increase of
GSH level and reversion of liver pathophysiology [63]. Valgimigli et al. [64] reported that ROS levels in HBV chronic
hepatitis patients were higher than in healthy controls by
radical probe electron paramagnetic resonance measurements
of human liver biopsy specimens.
Silymarin and Liver Transplantation
The experimental work of Ligeret et al. [65] with
silibinin deserves attention. They studied the effect of
silibinin on cold preservation-warm reperfusion injury of the
liver in rats. They found that silibinin reduced the signs of
oxidative stress in the hepatocytes and it increased the mitochondrial ATP values in comparison to the control livers.
Based on these, they suggest that it is worthwhile to take
silibinin into consideration for modern interventions such as
liver transplantation. In an ischemia/reperfusion experimental model, silymarin reduced ischemic renal damage in Wistar rats. The authors recommend that this propriety of sily-

Silymarin, Liver Diseases and Liver Cancer

Current Pharmaceutical Biotechnology, 2012, Vol. 13, No. 1

marin is worthwhile to be taken into account for the new

therapeutic strategies to prevent ischemia/reperfusion injuries [66].
SILYMARIN AND LIVER CANCER
HCC is the third most common cause of cancer-related
death worldwide. It can be found most frequently (80-90 %)
in patients with liver cirrhosis. The most frequent causes of
liver cirrhosis are chronic HBV [67] and HCV [68] infections and chronic alcohol consumption [69]. The occurrence
of HCC is about 3-15 % in patients with alcoholic liver disease. Other predisposing causes can be: NASH [70], obesity
[71], diabetes mellitus [72], autoimmune hepatitis, intrahepatic biliary inflammations (primary biliary cirrhosis and
primary sclerosing cholangitis), copper and iron metabolic
diseases (Wilson disease, haemochromatosis), and congenital
alpha-1-antitripsin deficiency.
Silymarin was widely studied for preventing HCC [73].
Some of these experimental in vitro and in vivo studies are
listed in Table 1. The biologically most active flavonoid,
silibinin, inhibits cytochrome P4502E1 induction, ethanol
metabolism and ROS generation in HCC cells in vitro. These
silibinin-mediated effects also inhibit ethanol-dependent
increases in HCC cell proliferation in culture [74].
Ramakrishnan et al. [75] have demonstrated that silymarin
treatment inhibited the proliferation and induced apoptosis in
the human HCC cell line HepG2.
Experiments were performed in order to investigate the
effect of silymarin on the serum lipid components, free fatty
acid levels and cyclooxygenase (COX-2) expression in rats
with N-nitrosodiethylamine (NDEA)-induced HCC. Rats
with NDEA-induced HCC developed severe hyperlipidemia
that evolved in consequence of an expression overregulated
by COX-2 as demonstrated by Western blotting and immunohistochemical analytic methods. Administration of silymarin in rats significantly attenuated hyperlipidemia and the
expression overregulated by COX-2. Based on this, the
Table 1.

213

authors recommend the increased use of silymarin as an adjuvant chemopreventive agent in the prevention of cancerous
diseases of the liver [38]. Silymarin exerted beneficial effects
on liver carcinogenesis by attenuating the recruitment of
mast cells which are involved in invasion and angiogenesis
and thereby decreased the expressions of matrix metalloproteinase (MMP)-2 and MMP-9 [76]. The same research
group investigated the efficacy of silymarin on the antioxidant status of NDEA-induced hepatocarcinogenesis in Wistar albino male rats. Silymarin reduced the lipid peroxidation
status, increased the levels of GSH and the activities of antioxidant enzymes. These findings suggested that silymarin
suppressed NDEA-induced hepatocarcinogenesis by modulating the antioxidant defense status [77]. In addition silymarin treatment in the other study significantly attenuated
the alterations of the level of alpha-fetoprotein (AFP), carcinoembrional antigen (CEA), activities of liver enzymes, and
decreased the levels of malondialdehyde (MDA)-DNA adduct
formation. Silymarin could be developed a promising chemotherapeutic adjuvant for the treatment of liver cancer [78].
SILYMARIN AND EXTRAHEPATIC CANCERS
The anticancer effects of silymarin in non-hepatic tumors
has been established in several studies using in vitro and in
vivo methods; it can exert a beneficial effect on the balance
of cell survival and apoptosis with interfering cytokines
regulating cell cycle and proteins influencing apoptosis
[79,80]. In addition to this, anti-inflammatory activity and
inhibitory effect of silymarin on the development of metastases have also been detected. Recently, silibinin have also
been shown to exert significant anti-neoplastic effects in a
variety of in vitro and in vivo cancer models, including skin,
breast, lung, gastric, colon, bladder, prostate and kidney carcinomas. Some of the tumors in which silymarin had beneficial effect are demonstrated in Table 2. Silibinin inhibits
colorectal cancer growth by inhibiting tumor cell proliferation and angiogenesis [81] and the invasion of human lung

Liver Cancer Prevention and Treatment with Silymarin

Study Type

Experimental Model

Mechanisms

References

In vitro

HCC cell culture

 Cytochrome P4502E1;
 ethanol metabolism;
ROS generation

[74]

In vitro

HepG2 cell line

 Proliferation;

Apoptosis;
cytosolic cytochrome c

[75]

In vivo

NDEA-induced rat hepatocarcinogenesis

 Levels of lipid peroxides;
GSH;
activities of antioxidant enzymes

[77]

In vivo

NDEA-induced rat hepatocarcinogenesis

 MDA-DNA adducts;
 AFP;  CEA;  ALT; AST

[78]

In vivo

NDEA-induced rat hepatocarcinogenesis

 COX-2;
 hyperlipidemia

[38]

In vivo

NDEA-induced rat hepatocarcinogenesis

 MMP-2;  MMP-9

[76]

Abbreviations: AFP,
-fetoprotein; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CEA, carcinoembrional antigen; COX-2, cyclooxygenase-2; GSH, glutathione; HCC, hepatocellular carcinoma; MDA, malondialdehyde; MMP, metalloproteinase; NDEA, N-nitrosodiethylamine; ROS, reactive oxygen species.

214 Current Pharmaceutical Biotechnology, 2012, Vol. 13, No. 1

Table 2.

Fehr and Lengyel

Sylimarin as Chemopreventive and Therapeutic Agent for Extra-Hepatic Tumors

Organ/System

Target/Effects

Mechanisms

References

Reduces the risk of skin cancers initiated with UVradiation

 Inflammation;  oxidative stress;  DNA-damage

[87]

Protective effect against chemotherapeutic agent

mitomycin C-induced cell death in human melanoma
A 375- S2 cells

 Mitochondria mediated apoptosis;  p53;  Bcl-2

[88]

Prevents TPA-induced
MMP-9 expression in human breast cancer cells

 MMP-9;  COX-2

[89]

Preventive effect of arsenite-induced cytotoxicity in

two human breast adeno- carcinoma cell lines

 Oxidative stress

[90]

Inhibits the invasion of human lung cancer cells

 Urokinase plasminogen activator;  MMP-2

[82]

Inhibits tumor growth in athymic nude mice

NF-B

[91]

Suppresses TNF-
- induced MMP-9

expression in gastric cancer cell line

MMP-9
MEK/ERK pathway

[92]

Suppresses spontaneous tumorgenesis in

APC min/+) mice

 Beta- catenin;  cyclin D1;  proliferation;

 apoptosis;
 c-Myc;  phospho-glycogen synthase kinase 3 beta;
 COX-2; NOS

[93, 94]

Suppresses 1,2-dimethyl-hydrazine-induced carcinogenesis

Modulation of biotransforming activity of microbial

enzymes

[95]

Inhibits the growth of LoVo cells

 Apoptosis;  Caspases 3, 9;
 poly (ADP-ribose) polymerase

[96]

Causes strong cell cycle arrest at G(1), G(2)-M-phase

 Cyclins;  cyclin-dependent kinases (1, 2, 4, 6); 

cyclin dependent kinase inhibitor (p21, p27);  phosphorilation of retinoblastoma protein

[96]

Inhibits proliferation and promotes cell-cycle arrest

 Angiogenesis;  NOS;
 COX; HIF-1
;  VEGF;
 proliferation;  apoptosis

[97, 98]

Prostate

Inhibits cell proliferation in PC3 prostate carcinoma

cell line

 Proliferation;  HIF-1

[99, 100]

Bladder

Inhibits the proliferation of RT4 human bladder papilloma cells and of bladder tumor xenograft in mice

 Survivin protein;  p53

[101]

Inhibits invasive properties of U87MG cells

 Cathepsin B; NF-B;
 MMP-9;  gelatinase B;
 urokinase plasminogen
Activator receptor;  urokinase plasminogen activator;
 intercellular adhesion molecule 1;  stefin A

[102]

Skin

Breast

Lung

Gastrointestinal tract

Other systems

Abbreviations: COX-2, cyclooxygenase-2; HIF-1
, hypoxia-inducible factor-1
; MMP-2/9, metalloproteinase-2/9, NF-B, nuclear factor-kappaB; NOS, nitric
oxide synthase; TPA, 12-O-tetradecanoylphorbol-13-acetate; VEGF, vascular endothelial growth factor.

cancer cells via decreased production of urokinaseplasminogen activator and MMP-2 [82]. The alleviating effect of silymarin, particularly silibinin has also been demonstrated in relation to the reduction of cellular injury due to
chemotherapeutic agents or radiotherapy [83]. This can obviously be explained by the free radical scavenger propriety
of silymarin. Its possible inhibitory effects on neoplastic
processes are summarized in Fig. (2) based on the publication of Ramasamy et al. [84].

Li et al. [85] examined the pharmacokinetics, mechanisms, effectiveness and adverse effects of silibinin's anticancer actions reported to date in pre-clinical and clinical
trials. The silibinin as an adjunct cancer treatment is able to
influence such factors as histological subtype, hormonal
status, stromal interactions and drug metabolizing gene polymorphisms. The results of these studies may help to more
precisely target and dose silibinin therapy to optimize clinical outcomes for oncology patients [86].

Silymarin, Liver Diseases and Liver Cancer

Current Pharmaceutical Biotechnology, 2012, Vol. 13, No. 1

215

REFERENCES
[1]
Influence of cell
cycle

[2]
[3]
[4]

Silymarin

[5]

[6]
Inhibition of
invasive
infiltration and
the development
of metastases

[7]

[8]
[9]

Fig. (2). Potential anticarcinogenic effects of silymarin [adapted

from ref. 34].

[10]

CONCLUSIONS
Numerous studies as presented here suggest that silymarin may be useful in the treatment of patients with chronic
liver diseases, which are risk factors for cirrhosis and HCC,
especially alcoholic and non-alcoholic steatohepatitis in the
current clinical practice and, as it can be expected, also in the
future. In addition it can also be administered as adjuvant
therapy in the chemoprevention of other cancerous diseases.
The very marked viral load reducing effect of silibinin at
high doses also deserves special attention. The molecular
mechanisms of silibinin-mediated antiproliferative effects
are mainly via receptor tyrosine kinase, androgen receptor,
signal transducers and activators of transcription, NF-
B,
cell cycle regulatory and apoptotic signaling pathways in
various cancer cells. Targeting inhibition of proliferative
pathways through silibinin treatment may provide a new
approach for improving chemopreventive and chemotherapeutic effects.
Milk thistle is the dietary supplement taken most frequently by patients with chronic liver diseases. This supplement is one of the most widely used herbal medicines for a
long time. Both milk thistle and its active ingredient silymarin are pharmacologically safe and well tolerated. This
review demonstrates that silymarin is a safe and effective
antioxidant drug in animal model systems, and further human studies are needed to establish its full potential for the
treatment of chronic liver diseases as well as liver cancer
prevention.

[11]

[12]

[13]
[14]

[15]

[16]
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ACKNOWLEDGEMENT
The studies conducted by the authors as mentioned in this
review was supported by the EU Project COST B35 Action:
Lipid Peroxidation Associated Disorders: LPO.

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Received: May 02, 2010

Revised: August 31, 2010

Accepted: September 01, 2010

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