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Abstract

Milk thistle (Silybum marianum) is an herbal supplement used to treat liver and biliary disorders. Silymarin, a mixture of flavanoid complexes, is the active component that protects liver and kidney cells from toxic effects of drugs, including chemotherapy. Although milk thistle has not significantly altered the course of chronic liver disease, it has reduced liver enzyme levels and demonstrated anti-inflammatory and T cell-modulating effects. There is strong preclinical evidence for silymarin's hepatoprotective and anticarcinogenic effects, including inhibition of cancer cell growth in human prostate, skin, breast, and cervical cells. Milk thistle is considered safe and well-tolerated, with gastrointestinal upset, a mild laxative effect, and rare allergic reaction being the only adverse events reported when taken within the recommended dose range. More clinical trials of rigorous methodology, using standardized and well-defined products and dosages, are needed to evaluate the potential of silymarin against liver toxicity, chronic liver disease, and human cancers.
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Integrative Cancer Therapies
DOI: 10.1177/1534735407301632
2007; 6; 104 Integr Cancer Ther
Janice Post-White, Elena J. Ladas and Kara M. Kelly
)Silybum marianumAdvances in the Use of Milk Thistle (
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104 INTEGRATIVE CANCER THERAPIES 6(2); 2007 pp. 104-109
Advances in the Use of Milk Thistle
(Silybum marianum)
Janice Post-White, RN, PhD, FAAN, Elena J. Ladas, MS, RD, and Kara M. Kelly, MD
Milk thistle (Silybum marianum) is an herbal supplement used
to treat liver and biliary disorders. Silymarin, a mixture of
flavanoid complexes, is the active component that protects
liver and kidney cells from toxic effects of drugs, including
chemotherapy. Although milk thistle has not significantly
altered the course of chronic liver disease, it has reduced
liver enzyme levels and demonstrated anti-inflammatory and
T cell–modulating effects. There is strong preclinical evi-
dence for silymarin’s hepatoprotective and anticarcinogenic
effects, including inhibition of cancer cell growth in human
prostate, skin, breast, and cervical cells. Milk thistle is con-
sidered safe and well-tolerated, with gastrointestinal upset,
a mild laxative effect, and rare allergic reaction being the
only adverse events reported when taken within the recom-
mended dose range. More clinical trials of rigorous method-
ology, using standardized and well-defined products and
dosages, are needed to evaluate the potential of silymarin
against liver toxicity, chronic liver disease, and human cancers.
Keywords: milk thistle; silymarin; cancer; liver disease; mecha-
nism; safety; efficacy
What Is Milk Thistle?
Milk thistle is available in the United States as a dietary
supplement. The fruit and seeds of the milk thistle
plant have been used for more than 2000 years as a
treatment for liver and biliary disorders. The seeds are
the medicinal part of the plant,
1
which is indigenous
to Europe but also can be found in the United States
and South America.
The botanical name for milk thistle is Silybum mari-
anum (L.) Gaertn., a member of the plant family
Asteraceae. The active constituent of milk thistle is sily-
marin, a mixture of flavonolignans comprised of 4 iso-
mers: silibinin, isosilibinin, silichristin, and silidianin.
Most supplements are standardized according to their
silibinin (often called silybin) content. In turn, silibinin
and isosilibinin are both mixtures of 2 diastereomers,
silibinin A and B and isosilibinins A and B, respectively.
2
Because of milk thistle’s lipophilic nature, it is usually
administered in capsule or tablet form rather than as an
herbal tea. Special formulations of silibinin have been
developed to enhance the bioavailability of the herbal
product; these forms are sold as a dietary supplement
under the names Legalon, Silipide, and Siliphos. As
a supplement, milk thistle is regulated as a food and
has not been approved by the US Food and Drug
Administration as a treatment for cancer or for any
other medical condition.
History of Use of Milk Thistle
The oldest reported use of milk thistle was by
Dioscorides, who recommended the herb as a treat-
ment for serpent bites. Pliny the Elder (
AD 23-79)
reported that the juice of the plant mixed with honey
was indicated for “carrying off bile.” Milk thistle was
first revered as an antidote for liver toxins in the
Middle Ages
3,4
and was later used by the British herbal-
ist Culpepper to relieve obstructions of the liver.
3,4
In
1898, Eclectic physicians Felter and Lloyd recognized
that the herb was good for “congestion” of the liver,
spleen, and kidney.
3,4
Native Americans have used
milk thistle to treat boils and other skin diseases.
Homeopathic practitioners have used preparations
from the seeds to treat a variety of illnesses, including
jaundice, gallstones, peritonitis, hemorrhage, bronchi-
tis, and varicose veins,
4
and currently use milk thistle to
treat liver dysfunction. The German Commission E rec-
ommends its use primarily for dyspeptic complaints
and liver conditions, including toxin-induced liver
damage and hepatic cirrhosis, and as a supportive ther-
apy for chronic inflammatory liver conditions.
5
Reasons for Milk Thistle Use Today
In the United States, milk thistle is 1 of the most fre-
quently sold herbal products. In 2000, retail sales of
Advances in Milk Thistle
DOI: 10.1177/1534735407301632
JPW is at the University of Minnesota, Minneapolis, Minnesota.
EJL is at the Division of Pediatric Oncology, Columbia University
Medical Center, New York, New York. KMK is at the Division of
Pediatric Oncology, Columbia University Medical Center, New York,
New York.
Correspondence: Janice Post-White, RN, PhD, FAAN, University
of Minnesota, 707 Kenwood Parkway, Minneapolis, MN 55403.
E-mail: postw001@umn.edu.
© 2007 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution.
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Advances in Milk Thistle
INTEGRATIVE CANCER THERAPIES 6(2); 2007 105
milk thistle were $8.9 million, a 14% increase over
1999. Patients use milk thistle in a variety of clinical
settings, but it is most commonly used in gastroin-
testinal clinics to help treat hepatitis and cirrhosis.
Despite a paucity of clinical trials investigating the
safety of milk thistle in the oncology setting, surveys
have found that milk thistle is one of the most com-
monly prescribed hepatoprotectants among individ-
uals with cancer. Patients and practitioners report
using milk thistle to aid the liver in detoxification,
anticipating that milk thistle may help clear toxins
from the blood and potentially aid them in tolerating
cancer therapy. This concept was initially proposed
in a case study and has subsequently been supported
by 1 clinical trial that was conducted among children
with acute lymphoblastic leukemia.
6
Milk thistle also may have cancer cytotoxic effects.
One phase III clinical trial in adult men with prostate
cancer reported delays in rising prostate specific anti-
gen levels compared with placebo.
7
This series will
present both preclinical and clinical studies demon-
strating the potential role of milk thistle as a hepato-
protectant and an anticancer agent. Although most of
the cancer investigations are in the preclinical stage,
phase I/II studies suggest potential efficacy and few
adverse events. No other medications or supplements
are currently available that preserve liver function
and provide clinical benefits.
In their article in this issue, Greenlee and col-
leagues
8
provide an overview of current clinical appli-
cations of milk thistle and studies supporting its use in
the oncology setting. They also present rationales and
preliminary studies supporting the use of milk thistle
in cardiovascular, renal, and diabetic conditions.
Mechanisms of Action
Silymarin is most well known for its antioxidant and
chemoprotectant effects on the liver. It is highly
absorbed after oral ingestion and has a strong first-pass
effect through the liver. In laboratory studies, silibinin
has been found to stabilize cell membranes, thus pre-
venting toxic chemicals from entering the cell
9-12
and
exporting toxins out of the cell before damage ensues.
9-15
Administration of silymarin to rats challenged with a
toxin resulted in higher levels of glutathione in liver
cells, decreased oxidative stress (measured by malondi-
aldehyde concentrations), and fewer elevations in liver
enzyme tests (aspartate aminotransferase [AST]/ala-
nine aminotransferase [ALT]).
13
Silibinin also has been
shown to stimulate or inhibit phase I detoxification
pathways,
16,17
stimulate phase II detoxification path-
ways,
18
and accelerate liver cell regeneration by stimu-
lating DNA synthesis precursors and enhancing
cellular enzyme production.
19-22
In their article in this issue, Comelli and colleagues
23
propose a unifying mechanism of action for silymarin
that demonstrates how its scavenging and antioxidant
properties reduce free radical generation, inhibit
nuclear factor-κB and tumor necrosis factor induction,
and balance the cascade of transcriptional processes
that affect cell growth and apoptosis, thereby reducing
inflammation and supporting the liver’s tolerance to
oxidative stress. These authors conclude that the use of
silymarin before or early after a toxic insult is more
likely to provide stronger protective effects than in
chronic liver disease.
There is strong preclinical evidence through in
vitro and in vivo models that silymarin (more specifi-
cally, the silibinin flavonoid components) interferes
with promotion and progression of cancer. In preclin-
ical studies, silymarin appeared to have direct anti-
cancer effects against prostate, breast, and ectocervical
tumor cells.
24,25
When the silibinin flavonoid compo-
nent was tested in vitro, it enhanced the efficacy of cis-
platin and doxorubicin against ovarian, breast, and
prostate cancer cells
26-28
and was synergistic with vin-
cristine, but not L-asparaginase, against CCRF-CEM
T cell, acute lymphoblastic leukemia cell lines.
29
When
tested in vitro, silibinin did not stimulate growth in sev-
eral cancer cell lines, including leukemia, colon (Caco-2),
and hepatoma (HepG2).
30
In their article in this issue, Deep and Agarwal
31
describe their and others’ numerous studies showing
the efficacy of silymarin and its flavonoid components
against skin and prostate cancer and synergistic effects
with chemotherapy and their work to identify the asso-
ciated molecular mechanisms. The potential clinical
efficacy, along with no known negative interactions
with chemotherapy agents, lack of toxicity to normal
cells, and ready absorption after oral administration,
suggests silymarin’s potential as a chemopreventive,
protective, and therapeutic agent.
One of the limitations of silymarin studies is the lack
of standardization of products and components. In this
issue, Kroll and colleagues
32
clearly define the need to
use consistent nomenclature and define the actual
components and composition of products tested
because each component may have different biological
effects. Another limitation is the variation in doses used
in clinical trials. Kroll and colleagues
32
emphasize the
need to conduct adequate pharmacokinetic analyses to
determine pharmacological concentrations of the
product that correlate with plasma and tissue concen-
trations and desired in vitro and in vivo effects.
Although some preliminary studies of pharmacokinet-
ics and pharmacodynamics of milk thistle extracts have
been conducted, additional studies are needed to
define bioavailability and concentrations required to
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Post-White et al
106 INTEGRATIVE CANCER THERAPIES 6(2); 2007
produce biological and clinical effects, with considera-
tion for potential interaction with chemotherapy drugs
metabolized through cytochrome P450 isoenzyme
(CYP) pathways, particularly when higher dosages of
milk thistle extracts are administered.
Evidence for Safety and Efficacy
Efficacy
Most early clinical trials investigated milk thistle’s effec-
tiveness in the treatment of patients with hepatitis, cir-
rhosis, or biliary disorders.
33-40
These studies used a
wide range of products and doses (120-560 mg/d) and
yielded conflicting results. In one of the largest obser-
vational studies, involving 2637 patients with chronic
liver disease, 8 weeks of silymarin (560 mg/d) reduced
serum AST, ALT, and gamma-glutamyl-transpeptidase
(a marker of bile duct disease) and decreased the fre-
quency of palpable hepatomegaly.
41
Other more recent
studies have shown no effects.
42-44
In other reports,
reviewed in this issue by Greenlee and colleagues,
8
milk
thistle was used to treat hyperlipidemia, diabetes melli-
tus,
40
and Amanita phalloides mushroom poisoning.
10,45
In their article in this issue, Tamayo and Diamond
46
review clinical trials of milk thistle extracts conducted
in the past 5 years. Although milk thistle has not signif-
icantly altered the course of chronic liver disease, it has
reduced liver enzymes in some studies and exhibited
select effects on anti-inflammatory measures in chronic
liver disease and diabetes mellitus.
46,47
Milk thistle has only recently begun clinical trial
testing in cancer. Two clinical trials have followed in
the footsteps of 2 well-publicized case studies.
48,49
In 50
children with acute lymphoblastic leukemia (ALL)
with grade 2 or greater chemotherapy-related hepato-
toxicity, milk thistle (Siliphos 5.1 mg/kg/d) was asso-
ciated with a significant reduction in AST and a trend
in reduction of ALT levels after 56 days.
6
In a phase III
trial of men with prostate cancer, silymarin (160 mg/d
for 10 weeks), in conjunction with soy isoflavones and
other antioxidants, delayed prostate specific antigen
level increases, whereas the placebo group had a
2.6-fold increase.
50
Safety
Milk thistle has been used safely during pregnancy,
51
in
children,
6,10
and in adults older than 75 years.
52
There
were no reported toxicities at doses of 560 mg/d
for pregnant women with intrahepatic cholestasis,
20 to 50 mg/kg body weight intravenously for children
with mushroom poisoning, and 420 mg/d in older
adults.
52
One recent phase I study suggested that 13 g
of Siliphos (30% silibinin) was the recommended
tolerated dose, with hyperbilirubinemia observed in
higher doses (15-20 g/d).
53
However, as Dr. Kroll and
colleagues
32
address in their article, these large doses
are not recommended for patients receiving cancer
chemotherapy because such doses may interact with
chemotherapy metabolized through CYP pathways.
Although toxicities were not observed in doses up to
1200 mg/d,
44
most clinical studies continued to test
smaller dose ranges of 160 to 600 mg/d, divided into
3 daily doses.
46
Absorption is rapid, with peak plasma
levels occurring within a few hours and an elimina-
tion half-life of 6 hours.
54
Because of the short half-
life, it is recommended that milk thistle be taken in 3
divided doses throughout the day. Silibinin is pre-
dominantly excreted in bile (80%), with the remain-
der secreted in the urine.
Silymarin has been shown to decrease cytochrome
P450 enzyme activity, potentially affecting clearance of
some chemotherapy drugs.
17
However, this inhibition
was not observed with oral intake of milk thistle,
16
and
no interference with several chemotherapy agents (cis-
platin, doxorubicin, vincristine, L-asparaginase) has
been shown in preclinical studies at the concentra-
tions used.
26-29
Several recent studies report no interac-
tion with chemotherapy agents or interference with
enzymes involved in metabolism of drugs (CYP3A,
CYP1A2, CYP2D6, CYP2Ea, UGT1A1, P-glycoprotein)
(reviewed in this issue by Tamayo and Diamond
46
).
These effects may be dose responsive, however, and
require further study at higher dosages.
32
Adverse Events
Milk thistle is considered safe and well-tolerated, with
reported adverse events similar to placebo.
47,55,56
Although infrequent, the most commonly reported
adverse events are a mild laxative effect and gastroin-
testinal upset.
57
Mild allergic reactions were reported
at doses greater than 1500 mg/d.
1
According to the
German Commission E, there are no reported side
effects of milk thistle within the recommended dose
range.
5
Milk thistle appears to be safe for up to 41
months of use.
55
In a systematic review of 13 clinical trials involving
915 subjects, there were no effects on mortality or
complications of alcohol-induced or virally induced
chronic liver disease. Milk thistle was not associated
with an increased risk of adverse events compared
with placebo (3.5% vs 4.4% in placebo). The symp-
toms reported in both groups were pruritus, nausea
and epigastric distress, and headache.
47
Research Strengths and Weaknesses
There is strong preclinical evidence through in vitro
and in vivo models that silymarin protects and regener-
ates liver and kidney cells and interferes with promo-
tion and progression of cancer. Some of these effects
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Advances in Milk Thistle
INTEGRATIVE CANCER THERAPIES 6(2); 2007 107
may be dose related. Milk thistle’s effect on clinical out-
comes is not well established, and reported effects on
liver enzyme levels are inconsistent and inconclusive.
The methodological quality of the majority of the
clinical trials conducted in patients with chronic liver
disease is low, with most of the studies including het-
erogenous populations, lacking in standardized prepa-
rations, and having poorly defined nonobjective
endpoints.
58
When high-quality trials were analyzed
apart from low-quality trials, the beneficial effect of
milk thistle on liver enzymes was lessened,
47
suggesting
either a lack of effect, sample bias, or type I error in
lower quality studies. This review excluded acute liver
disease, including studies of drug or mushroom toxi-
city. Considering that most of the reported clinical tri-
als tested milk thistle in chronic liver disease and that
the biological effects may be more active in an acute
model,
23,31
additional clinical trials are needed to test
efficacy of milk thistle as a hepatoprotectant and treat-
ment for acute liver-related disorders. Such efficacy tri-
als should ensure sample sizes sufficient for power,
randomization and inclusion of a placebo/reference
group, blinding of assessors and subjects, standardized
dose and product, and intention-to-treat analyses.
Oftentimes, randomized controlled trials are done
under controlled and ideal conditions and may fail to
account for real-life practices in which supplements
are taken with many other over-the-counter and pre-
scription medications.
59
Individual subject character-
istics and practices, such as use of other herbs and
supplements, should be controlled for or assessed
and considered as potential covariates in the clinical
efficacy trials.
60
Although systematic reviews and ran-
domized controlled trials are considered the best evi-
dence for practice, making clinical decisions to add
milk thistle requires consideration of the quality of
the studies and clinical judgment.
Summary
Silymarin functions as a potent antioxidant that stabi-
lizes cell membranes, stimulates detoxification path-
ways, regenerates liver tissue, inhibits the growth of
some cancer cell lines, exerts direct cytotoxic activity
toward select cancer cell lines, and increases the effi-
cacy of some chemotherapy agents. The action of sily-
marin involves multiple mechanisms affecting the liver
and other digestive organs. Unlike other herbs, milk
thistle has strong preclinical evidence for hepatopro-
tective and anticarcinogenic effects. It has yet to be
determined, however, whether milk thistle yields
better clinical outcomes. The potential of milk thistle
as a hepatoprotectant and adjuvant to chemotherapy
requires further clinical trial testing with standardized
products and quality controls.
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... Used to treat liver and biliary disorders. [162] 16 ...
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Indian Himalayan region (IHR) supports a wide diversity of plants and most of them are known for their medicinal value. Humankind has been using medicinal plants since the inception of civilization. Various types of bioactive compounds are found in plants, which are directly and indirectly beneficial for plants as well as humans. These bioactive compounds are highly useful and being used as a strong source of medicines, pharmaceuticals, agrochemicals, food additives, fragrances, and flavoring agents. Apart from this, several plant species contain some toxic compounds that affect the health of many forms of life as well as cause their death. These plants are known as poisonous plants, because of their toxicity to both humans and animals. Therefore, it is necessary to know in what quantity they should be taken so that it does not have a negative impact on health. Recent studies on poisonous plants have raised awareness among people who are at risk of plant toxicity in different parts of the world. The main aim of this review article is to explore the current knowledge about the poisonous plants of the Indian Himalayas along with the importance of these poisonous plants to treat different ailments. The findings of the present review will be helpful to different pharmaceutical industries, the scientific community and researchers around the world.
... Silymarin, an extract from the seeds of the milk thistle (Silybum marianum), of Mediterranean origin, contains a gamma of flavolignans such as silybin, isosilybin, silychristin, and silydianin [52]. Silymarin has been credited with having effects on liver disorders, in addition to anticancer, antihepatoprotector, antihyperlipidemic, antidiabetic, antiamnesic, anti-inflammatory, and antisclerotic activities, and it modulates T cells [53][54][55]. It has been considered effective for the symptoms of respiratory diseases, fever, and influenza [56]. ...
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Background: Metabolic syndrome (MetS) has increased worldwide, and since 2012, prevalence of obesity, hypertension, diabetes, and dyslipidemia has increased in Mexico. Objective: To assess the prevalence of MetS, and its relationship with sociodemographic and lifestyle factors among Mexican adults. Methods: Analytical cross-sectional study nationally representative, carried out on Mexican adults (≥20-year-old adults of both sexes; n = 4595). Socioeconomic factors, geographic area, health care coverage and previous medical diagnoses of diabetes and hypertension, and smoking were assessed. Anthropometrics, and triglyceride, total cholesterol, high-density lipoprotein cholesterol (HDL-chol), creatinine, and glucose plasma levels were measured. The ATP III MetS definition was applied. Results: A MetS prevalence of 44.2% was observed, which was higher in males than females, and increased with age, lower school level, and overweight. Hyperglycemia, hypertriglyceridemia, low HDL-chol, abdominal obesity, and hypertension were higher in people with MetS, and were associated with obesity. Conclusions: The prevalence of MetS in the Mexican adult observed in the ENSADER 2007 was high, and mainly in men than women. Specific associations of MetS with age, scholar level, and body mass index have been found. Obesity and MetS were associated.
... Silibinin, a polyphenolic flavonoid, is the main active component extracted from the seed of silybum marianum (milk thistle) or artichoke (cynara scolymus) (167). Previous studies have reported silibinin confers protective advantage in improving both liver and cerebral function after I/R, which raises concern about the role of silibinin against reperfusion injury in other tissues, especially in myocardium (168,169). ...
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Percutaneous coronary intervention (PCI) is one of the most effective reperfusion strategies for acute myocardial infarction (AMI) despite myocardial ischemia/reperfusion (I/R) injury, causing one of the causes of most cardiomyocyte injuries and deaths. The pathological processes of myocardial I/R injury include apoptosis, autophagy, and irreversible cell death caused by calcium overload, oxidative stress, and inflammation. Eventually, myocardial I/R injury causes a spike of further cardiomyocyte injury that contributes to final infarct size (IS) and bound with hospitalization of heart failure as well as all-cause mortality within the following 12 months. Therefore, the addition of adjuvant intervention to improve myocardial salvage and cardiac function calls for further investigation. Phytochemicals are non-nutritive bioactive secondary compounds abundantly found in Chinese herbal medicine. Great effort has been put into phytochemicals because they are often in line with the expectations to improve myocardial I/R injury without compromising the clinical efficacy or to even produce synergy. We summarized the previous efforts, briefly outlined the mechanism of myocardial I/R injury, and focused on exploring the cardioprotective effects and potential mechanisms of all phytochemical types that have been investigated under myocardial I/R injury. Phytochemicals deserve to be utilized as promising therapeutic candidates for further development and research on combating myocardial I/R injury. Nevertheless, more studies are needed to provide a better understanding of the mechanism of myocardial I/R injury treatment using phytochemicals and possible side effects associated with this approach.
... Although there are not many studies evaluating the toxic effect, cancer is prescribed hepatoprotectically for the use of individuals. For example, studies on prostate cancer are known to reduce the level of PSA antigens (Post-White, Ladas ve Kelly, 2007). Many have been in the early experimental trial, but have investigated its effectiveness in treating patients with hepatitis, cirrhosis, or biliary disorders ( Angulo vd., 2000;Ferenci vd., 1989;Lucena vd., 2002;Parés vd., 1998;Post-White vd., 2007;Salmi ve Sarna, 1982). ...
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The use of herbs that are known to be medically useful in the field of traditional and complementary medicine has been widely used as a mixture in different proportions. Material and temporal restrictions in drug production provide a significant benefit in terms of using supportive herbal ingredients instead of treatment. However, when creating these components, it is necessary to determine the nontoxic dose in many areas, from the origin of plants to the active substance and the dose range that can be used. In this study, acute and subacute toxicity analyzes of DVD-REG ® herbal supplements known to be used in Remember Regeneration Therapy Method (RTM) were performed. Clinical observation findings were evaluated according to ISO 10993-11:2017 standards and no changes were made between the control and application groups. Hematological and biochemical blood parameters were evaluated as control group, acute group, subacute group, and post-subacute group and no changes were found between the control and administration groups. There was no pathological finding among the groups in liver, heart, kidney and spleen tissues where histological toxicity was investigated. In this study, which are now used in Turkey food supplement data obtained from the DVD-REG ® was researched it will benefit for chronic effects of acute, subacute and post-subacute toxicity tests.
... Human studies have shown that milk thistle is generally nontoxic and cause no side effects when administered to adults in a dose range of 240 900mg/day in two or three divided doses. A higher dose (>1500mg/day) may produce a laxative effect which may be due to increased bile secretion and bile flow (Monograph, 1999). Most commonly noted adverse effects such as bloating, dyspepsia, nausea, irregular stool and diarrhea were observed in 2-10% of patients in clinical trials. ...
Thesis
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The objectives of the present project were to study the effect of methanolic extract of milk thistle leaves and bleomycin on tumor growth, some blood parameters, biochemical parameters, cytogenetic values (MI and BI) and histopathological changes in tumor mass and internal organs of treated animals. The experiment included the preparation of 70% alcoholic extraction of the plant, with a resultant yield of crude extract 10 %for 100 gm of leaves. Sixty female adult Swiss albino balb/c mice of approximately body weight (19-25g) and age (4-6) weeks were used in experiment. Blood parameters showed a significant increase (P˂0.05) in Hb, RBCs and WBCs counts in group treated with (350 mg/kg B.W) methanolic extract of Milk thistle leaves and groups treated with milk thistle leaves before treatment with bleomycin. While those parameters showed significance decrease (P˂0.05) in groups treated with bleomycin (15 mg/kg B.w)only. In case of differential count the results showed that lymphocytes numbers have significant increase in groups treated with methanolic extract of milk thistle while neutrophils numbers increased in group treated with bleomycin. Biochemical study showed that an improvement in liver enzymes activity and glucose level in milk thistle before treated groups with chemotherapeutic drug. In cytogenetic study two parameters were used, mitotic index (MI) and blastic index (BI) the result showed a significance increase (P˂0.05) in MI and BI in groups treated with methanolic extract of milk thistle. Also the result showed a significant decrease in these values in groups treated with bleomycin. b Two equations were used to measure the Tumor volume (Tv) and the percentage of Growth volume inhibition (Gv) to evaluate anticancer activity of the plant. The result of the study was showed a significant (P˂0.05) reduction in tumor volume as well as significant change (P˂0.05) in growth inhibition percentage in methanolic extract treated groups. The histopathological examination of untreated tumor showed extensive areas of necrosis and hemorrhage with infiltration of inflammatory cells (neutrophils) in tumor masses, with uncontrolled prolifration of cancer cells and a tendency to form gaint cells and acinar like structures with increase in mitotic figures. The tumor showed metastasis in liver with infiltration of tumor associated macrophages in liver and heart. Histopatological section in group of tumor –bearing female mice , treated with methanolic extract, were showed encapsulation of the tumor mass with fibrous connective tissue infiltrated with lymphocytes and vacuolation of cancer cells with hyperplasia of islet of langerhans and hemopoietic tissue, infiltration of mononuclear cells and perivascular cuffing in kidney, lung, with formation of early granuloma in liver and deposition of amyloid-like substance in spleen with focal gliosis. In chemotherapy treated group a severe pathological lesions in brain, lung, kidney, pancreas and bone marrow with pre-cancerous changes in liver were documented. On the other hand, groups treated with plant extract before chemotherapy showed marked improvement in hemoatological, biochemical and histopathological findings due to the immunomodulatory effect of the plant extract . In conclusion both methanolic extract of milk thistle leaves and bleomycin have cytotoxic effect on transplanted mammary tumor cells in mice, with no side effect in case of plant extract in comparsion with bleomycin cause severe pathological changes in internal organ with c depletion in hemopoietic tissue and formation of pre-cancerous lesion in liver and significant of some hematological, biochemical parameters and cytogenetic analysis. The study showed that administration of milk thistle leaves extract before chemotherapy plays a role in amelioration of all parameters monitored above.
... Features of its therapeutic are due to have silymarin in their composition (Qavami et al., 2013). Milk thistle (Silybum marianum) a well-known and commonly used herb for treating hepatic diseases, and has its possible greater patient acceptability (Post-White et al., 2007;Ghosh et al., 2010) Milk thistle constituents and seeds extract are hepatoprotective and antioxidant (Bhattacharya, 2011). Silymarin has been used to treat toxin-induced liver diseases, also alcoholic liver disease, acute and chronic viral hepatitis (Abenavoli et al., 2010). ...
Research
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Present of this study was designed to improve the antioxidant activity of milk thistle (salymarin) against inoculated mice with virulent strain of Corynebacterium Pseudotuberculosis by measuring the serum levels of Free Radicals Peroxinitrite and Malondialdhyde. Fifty mice were divided into five groups equally G1:10 mice served as control negative. G2 served as control positive challenged virulent C. pseudotuberculosis (5×10 9) CFU/ ml I/P. G3 giving plant extract of salybum marianam 350 mg / kg orally. G4 giving saly marin for thirty days and challenged with Corynebacterium pseudotuberculosis. G5 challenged with virulent C. pseudotuberculosis (5×10 9) CFU/ ml I/P after thirty days treated with plant extract for thirty days. At thirty days of experiment (5) mice were sacrefecied from each group and serum blood were collected for measuring oxidant levels (Peroxinitrite and Malondialdhyde), also at sixty days of experiment all animal were sacrificed to determine the free radicals level (Peroxinitrite and Malondialdhyde). The results revealed that the serum levels of free radicals in group treated with milk thistle lower than serum levels treated with Corynebacterium psedotuberculosis. This study concludes that the antioxidant activity of milk thistle in prevent and treatment the oxidative stress.
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Silibinin/silymarin has been used in herbal medicine for thousands of years and it is well-known for its hepato-protective properties. The present comprehensive literature review aimed to critically summarize the pharmacological properties of silymarin extract and its main ingredient silibinin in relation to classical cardiovascular risk factors (e.g., diabetes mellitus, etc.). We also assessed their potential protective and/or therapeutic application in cardiovascular diseases (CVDs), based on experimental and clinical studies. Pre-clinical studies including in vitro tests or animal models have predominantly implicated the following effects of silymarin and its constituents: (1) antioxidant, (2) hypolipidemic, (3) hypoglycemic, (4) anti-hypertensive and (5) cardioprotective. On the other hand, a direct amelioration of atherosclerosis and endothelial dysfunction after silymarin administration seems weak based on scarce data. In clinical trials, the most important findings are improved (1) glycemic and (2) lipid profiles in patients with type 2 diabetes mellitus and/or hyperlipidemia, while (3) the anti-hypertensive effects of silibinin/silymarin seem very modest. Finally, the changes in clinical endpoints are not robust enough to draw a firm conclusion. There are significant limitations in clinical trial design, including the great variety in doses and cohorts, the underlying conditions, the small sample sizes, the short duration and the absence of pharmacokinetic/pharmacodynamic tests prior to study commitment. More data from well-designed and high-quality pre-clinical and clinical studies are required to firmly establish the clinical efficacy of silibinin/silymarin and its possible therapeutic application in cardiovascular diseases.
Conference Paper
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Alternative medicine has become popular these days as it is gaining practices across the globe. Ayurvedic medicine is one of the important forms of alternative medicine that was widely available in India. The present study mainly focuses on the identification of therapeutic properties of Microstylis wallichii. The ethanolic extract of Microstylis wallichii roots are used for its anti-oxidant and antimicrobial activity. Microstylis wallichii dried roots shown good anti-oxidant and anti-microbial properties. The ethanolic extract of Microstylis wallichii was checked for anti-microbial activity against pathogenic bacteria such as E. coli, Staphylococcus aureus, Pseudomonas.
Chapter
Plants are incredibly significant in the lives of people around the world. People rely on plants to satisfy basic human needs like food, clothing, shelter, and health care. Because of a rising world population, increasing wages, and urbanization, these needs are growing rapidly. Of course, plants provide food directly and often feed livestock that is then eaten on their own. The value of plants is likely to become fairer among countries as world economies become more accessible and market-oriented through trade agreements such as those from the World Trade Organization. The socio-economic significance of such an understanding of plants is defined in this chapter by providing evidence of the multiple benefits of plant breeding in and beyond agriculture based on reproducible findings and scientific evidence for arable crops.
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Background: Milk Thistle (MT), an herbal plant widely used in Europe for treating liver and biliary disorders, is commonly self prescribed for its hepatoprotectant effects. Chemotherapy associated hepatotoxicity is a primary reason for dose reductions or withdrawal of chemotherapy in children with ALL. Purpose: To investigate the toxicity and efficacy of MT supplementation for treatment of hepatotoxicity in children with ALL during 1 maintenance chemotherapy phase. Methods: Children ages 1–21 yrs with ALL and grade 2 or greater hepatic toxicity (defined by elevations in AST, ALT, or total bilirubin (TB), by NCI CTC v2 criteria) were eligible for participation during a maintenance phase of chemotherapy by Childrens Oncology Group or Dana Farber Cancer Institute ALL protocols. Participants were randomized to MT (Siliphos®, Thorne Research, Dover, ID, 5.1mg/kg/day) or placebo orally for 28 days while receiving the prescribed chemotherapy. LFTs were evaluated at baseline, day 28 (end of supplementation) and day 56 (28 days after MT discontinuation). MT stability was assessed at onset and at 21 mos by HPLC with UV detection relative to standard curves and known retention times of authentic silybin A and B reference standards. CCRF-CEM T-cell ALL cell culture studies were conducted with MT and vincristine (V) or L-asparaginase (A). Results: 50 children, ages 1–19 yrs (median = 7) were enrolled. 1 child withdrew consent before treatment was initiated; 2 had insufficient data. No significant differences in age, gender, ethnicity, or treatment protocols were observed between the 2 groups. Adverse effects from MT/placebo were mild: diarrhea (2/3), anorexia (0/1), flatulence (1/0), abdominal pain (2/2), irritability (2/0). No differences between MT/placebo in grade 3/4 toxicities from chemotherapy were seen: heme-infectious (6/17), non-heme (10/6). Mean AST and ALT declined greater from baseline to day 28 with MT but the differences were not significant. A greater decrease in mean AST from baseline to Day 56 was observed with MT (78 to 47) compared to placebo (71 to 67) (p= 0.05). A trend towards a greater reduction in mean ALT from baseline to Day 56 with MT (187 to 122 vs placebo 140 to 139) was also seen (p=.07). More children in the MT group developed greater than a 50% reduction in TB at day 28 as compared to placebo (p = 0.0069). The decline in day 56 TB was greater with MT but the difference was not significant. MT was composed of 49.6% silybin A and 50.4% silybin B, with no change in total content and ratios at 21 mos. In T-cell ALL cell culture studies, no effect was observed on cytotoxicity with A, but MT enhanced V-mediated CEM cell kill. Conclusions: In children with ALL with established liver toxicity, MT supplementation for 28 days in conjunction with hepatotoxic chemotherapy is associated with significant reductions in LFTs compared with placebo. Future study will evaluate the effect of MT in allowing delivery of full doses of chemotherapy and its subsequent impact on leukemia-free survival, along with xenograft studies to determine whether the beneficial antileukemic potentiation of vincristine persists in vivo.
Article
Background: The role of silymarin in the treatment of liver cirrhosis is controversial. Aim: Clinical outcome, biochemical profile and the antiperoxidative effects of silymarin MZ-80 during 6 months treatment were investigated in patients with alcoholic liver cirrhosis. Methods: Sixty consecutive patients with alcoholic liver cirrhosis were randomized to receive either silymarin MZ-80 (S) (150 mg t.i.d. per day) or placebo (P) for periods of 6 months. Erythrocyte total glutathione (GSH) content, platelet malondialdehyde (MDA) and serum amino-terminal propeptide of procollagen Type III (PIIINP) were determined at baseline and at the end of treatment. Results: Forty-nine patients completed the study (24 S and 25 P). The 2 groups were well-matched for demographic as well as baseline clinical and laboratory parameters. Silymarin increased total GSH at 6 months (4.5 ± 3.4 to 5.8 ± 4.0 μmol/g Hb) whereas, in the placebo group, GSH remained unchanged (4.1 ± 3.9 to 4.4 ± 4.1 μmol/gHb) (p < 0.001), and platelet-derived non-induced MDA decreased by 33% (p <0.015). A parallel decrease in PIIINP values was seen with silymarin (1.82 ± 1.03 to 1.36 ± 0.5 U/ml, p < 0.033) but not with placebo (1.31 ± 0.4 to 1.27 ± 0.6 U/ml). There were no concurrent changes on laboratory indices of the pathology. Conclusions: Silymarin is well-tolerated and produces a small increase in glutathione and a decrease in lipid peroxidation in peripheral blood cells in patients with alcoholic liver cirrhosis. Despite these effects no changes in routine liver tests were observed during the course of therapy.
Article
PurposeMilk thistle, an herbal compound, is the dietary supplement taken most frequently by patients with chronic liver disease. We performed a systematic review of the literature to determine the efficacy and safety of this herb for the treatment of liver disease.
Article
Administration of silymarin (800 mg/kg i.p.) 30 min before carbon tetrachloride (18 μL/kg i.p.) did not modify total hepatic levels of CCl4 and metabolites in mice, but decreased by 40% the in vivo covalent binding of CCl4 metabolites to hepatic lipids at 2 hr. This pretreatment decreased by 60% the exhalation of ethane during the first hour after CCl4, and decreased by 50% the incidence of liver cell necrosis. In vitro, silymarin (800 μg/mL) decreased by 50 to 70% various monooxygenase activities, and decreased by 20% the covalent binding of CCl4 metabolites to microsomal proteins. Silymarin (800 μg/mL) decreased by 70% in vitro lipid peroxidation mediated by CCl4 metabolites, and decreased by 90% peroxidation mediated by NADPH alone. Silibinin, one of the three isomers composing silymarin, also decreased carbon tetrachloride-induced lipid peroxidation; this effect, however, was less than that of silymarin in vitro, and was more transient in vivo. Pretreatment with silibinin (800 mg/kg i.p.) 30min before CCl4 (18μL/kg i.p.) did not improve SGPT activity or liver histology at 24 hr. We conclude that silymarin prevents carbon tetrachloride-induced lipid peroxidation and hepatotoxicity in mice, firstly, by decreasing the metabolic activation of CCl4, and, secondly, by acting as a chain-breaking antioxidant.
Article
The incorporation of [3H] orotic acid into RNA from rat livers is stimulated by the flavonolignane derivative Silybin. The time course of the RNA synthesis and its dose dependence were demonstrated with isolated hepatocytes and [3H]uridine. The specific radioactivity of the newly synthesized RNA in rats treated with silybin is markedly higher than that of the controls. From preliminary experiments there is no indication that the synthesis of a distinct species of RNA is stimulated preferentially.