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A review of the bioavailability and clinical efficacy of milk thistle phytosome: A silybin-phosphatidylcholine complex (Siliphos®)

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Abstract and Figures

Certain of the water-soluble flavonoid molecules can be converted into lipid-compatible molecular complexes, aptly called phytosomes. Phytosomes are better able to transition from a hydrophilic environment into the lipid-friendly environment of the outer cell membrane, and from there into the cell, finally reaching the blood. The fruit of the milk thistle plant (Silybum marianum, Family Asteraceae) contains flavonoids that are proven liver protectants. The standardized extract known as silymarin contains three flavonoids of the flavonol subclass. Silybin predominates, followed by silydianin and silychristin. Although silybin is the most potent of the flavonoids in milk thistle, similar to other flavonoids it is not well-absorbed. Silybin-phosphatidylcholine complexed as a phytosome provides significant liver protection and enhanced bioavailability over conventional silymarin.
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Alternative Medicine Review u Volume 10, Number 3 u 2005 Page 193
Certain of the water-soluble flavonoid molecules
can be converted into lipid-compatible molecular
complexes, aptly called phytosomes. Phytosomes
are better able to transition from a hydrophilic
environment into the lipid-friendly environment
of the outer cell membrane, and from there into
the cell, finally reaching the blood. The fruit of
the milk thistle plant (Silybum marianum, Family
Asteraceae) contains flavonoids that are proven
liver protectants. The standardized extract known
as silymarin contains three flavonoids of the
flavonol subclass. Silybin predominates, followed
by silydianin and silychristin. Although silybin is the
most potent of the flavonoids in milk thistle, similar
to other flavonoids it is not well-absorbed. Silybin-
phosphatidylcholine complexed as a phytosome
provides significant liver protection and enhanced
bioavailability over conventional silymarin.
(Altern Med Rev 2005;10(3):193-203)
Most of the bioactive constituents of phyto-
medicines are avonoids (e.g., anthocyanidins from
bilberry, catechins from green tea, silymarin from
milk thistle). However, many avonoids are poorly
The poor absorption of avonoid nutrients
is likely due to two factors. First, they are multiple-
ring molecules too large to be absorbed by simple dif-
fusion, while they are not absorbed actively, as occurs
with some vitamins and minerals. Second, avonoid
molecules typically have poor miscibility with oils
and other lipids, severely limiting their ability to pass
A Review of the Bioavailability and
Clinical Efcacy of Milk Thistle Phytosome:
A Silybin-Phosphatidylcholine
Complex (Siliphos
Parris Kidd, PhD, and Kathleen Head, ND
across the lipid-rich outer membranes of the entero-
cytes of the small intestine.
Water-soluble avonoid molecules can be
converted into lipid-compatible molecular com-
plexes, aptly called phytosomes. Phytosomes are bet-
ter able to transition from a hydrophilic environment
into the lipid-friendly environment of the enterocyte
cell membrane and from there into the cell, nally
reaching the blood.
The lipid-phase substances
employed to make avonoids lipid-compatible are
phospholipids from soy, mainly phosphatidylcholine
(PC). PC, the principal molecular building block of
cell membranes, is miscible both in water and in oil/
lipid environments, and is well absorbed when taken
by mouth. Precise chemical analysis indicates a phy-
tosome is usually a avonoid molecule linked with
at least one PC molecule. A bond is formed between
the two molecules, creating a hybrid molecule. This
highly lipid-miscible hybrid bond is better suited to
merge into the lipid phase of the enterocyte’s outer
cell membrane.
Phosphatidylcholine is not merely a passive
“carrier” for the bioactive avonoids of the phyto-
somes, but is itself a bioactive nutrient with docu-
mented clinical efcacy for liver disease, including
Parris Kidd, PhD – University of California, Berkeley, PhD in cell biology;
contributing editor, Alternative Medicine Review; health educator; biomedical
consultant to the dietary supplement industry.
Correspondence address: 847 Elm Street, El Cerrito, CA 94530
Kathi Head, ND Technical Advisor, Thorne Research, Inc.; Editor-In-Chief,
Alternative Medicine Review.
Thorne Research is among the supplement manufacturers that supply Siliphos
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Page 194 Alternative Medicine Review u Volume 10, Number 3 u 2005
alcoholic hepatic steatosis, drug-induced liver dam-
age, and hepatitis.
The intakes of phytosome prepa-
rations sufcient to provide reliable clinical benet
often also provide substantial PC intakes.
Phytosomes are not liposomes; structurally,
the two are distinctly different. The phytosome is a
unit of several molecules bonded together, while the
liposome is an aggregate of many phospholipid mol-
ecules that can enclose active phytomolecules, but
without specically bonding to them.
The Mechanism of Hepatic
The liver is exceptionally vulnerable to toxic
attack as hepatocytes continually sort, separate, me-
tabolize, or store a variety of substances that reach
the liver directly following absorption into the blood.
Some, such as triglycerides and fat-soluble vitamins,
are packaged by the hepatocytes into lipoprotein par-
ticles and dispatched to other tissues. Others pose a
toxic threat until they can be detoxied. The livers
position immediately “downstream” from the intes-
tine puts it at risk from food-borne toxic agents. In
addition to food-borne toxins, such as herbicide and
pesticide residues, articial preservatives, and other
synthetic food additives, the liver must deal with oth-
er toxins that enter the body via diverse routes. These
can include alcohol, cigarette-smoke toxins, street
drugs, viral and bacterial antigens, heavy metals, sol-
vent pollutants, and over-the-counter and prescription
pharmaceuticals. During the detoxication process,
glutathione, the key antioxidant in the livers paren-
chymal cells, is directly or indirectly consumed.
The livers vulnerability to toxic agents is of-
ten compounded by its efforts to detoxify them. Its so-
phisticated cytochrome P450 enzyme system evolved
to detoxify and excrete excess amounts of hormones
and other substances that are naturally produced in
the body, as well as synthetic chemicals. However,
in attempting to neutralize certain toxins, P450 en-
zymes can chemically transform such substances,
making them more toxic. The consequence can be
uncontrolled depletion of glutathione and other anti-
oxidants, resulting in hepatocyte destruction.
Silybum marianum Contains Premier
Liver-Protectant Flavonoids
The fruit of the milk thistle plant (Silybum
marianum, Family Asteraceae) (Figure 1) contains
avonoids known for hepatoprotective effects.
antioxidant capacity of silymarin substantially boosts
the livers resistance to toxic insults.
Silymarin pri-
marily contains three avonoids of the avonol sub-
class (having a fully saturated C-ring). Silybin pre-
dominates (Figure 2), followed by silydianin and
silychristin. Silybin is actually a avonolignan, prob-
ably produced within the plant by the combination of
a avonol with a coniferyl alcohol. It is now known
that silybin is the most potent of the three.
protects the liver by conserving glutathione in the pa-
renchymal cells, while PC helps repair and replace
cell membranes.
These constituents likely offer the
synergistic benet of sparing liver cells from destruc-
tion. In its native form within the milk thistle fruit,
Figure 1. Silybum marianum
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Alternative Medicine Review u Volume 10, Number 3 u 2005 Page 195
silybin occurs primarily complexed with sugars, as a
avonyl glycoside or avonolignan. Silybin has been
extensively researched and found to have impressive
bioactivity, albeit limited by poor bioavailability.
Pharmacokinetics of Silybin-
Phosphatidylcholine Complex
In 1990, Malandrino et al succeeded in im-
proving the bioavailability of silymarin extract by
complexing it with soy PC a phytosome.
quently, a more puried silybin was complexed with
PC. The intermolecular bonding of silybin with PC
proved to be specic and stable, and the resulting
molecular complex is more soluble in lipophilic, or-
ganic solvents.
This property predicts the enhanced
ability of phytosomes to cross cell membranes and
enter cells.
Animal Studies
The superior bioavailability of silybin com-
plexed with PC over non-complexed silybin has
been documented through pharmacokinetic studies
conducted in rats and humans. Figure 3 illustrates
that, in rats, a large dose of silybin given orally as
plain silymarin remained virtually undetectable
in the plasma for the six-hour experiment.
marked contrast, when the same amount of silybin
(200 mg per kg body weight) was given as Sili-
, a silybin-PC phytosome, it was detected in
the plasma within minutes, and by one hour its lev-
els had peaked. Its plasma levels remained elevated
past the six-hour mark.
The superior absorption
of the silybin from Siliphos is re-
ected in its clearance in the urine.
Figure 4 illustrates the silybin from
Siliphos remained elevated at 70
hours following oral dosing, while
the silybin given alone barely rose
above detectable levels until after
25 hours.
Siliphos has been demon-
strated to reach the liver, its target
organ. Silybin was substantially
present in bile uid two hours fol-
lowing the administration of Sili-
phos and the liver continued to
secrete silybin into the bile during the entire study.
Silybin, given as the non-complexed silymarin, was
barely detectable in the bile during the same period.
From these single-dose, bioavailability stud-
ies several key points are evident. Silybin, when taken
Figure 2. Structure of Silybin
Figure 3. Relative Plasma Levels of Total Silybin in
Rats after Dosing with Siliphos or Non-complexed
Plasma Silybin
Non-phytosome Silybin
0 1 2 3 4 5 6
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by mouth, is poorly absorbed even at a very high in-
take (200 mg/kg body weight of the rat, equivalent to
a 16-gram dose for a 176-pound human). However,
when taken by mouth as phytosomes bound to PC,
silybin is well absorbed and detected in the blood
within the rst hour.
These rat studies yielded another important
nding – that phytosomal silybin rapidly reaches the
liver, traverses the liver cells, and appears in the bile
within two hours. The amount of silybin reaching the
bile from phytosome dosing is at least 6.5 times great-
er than that from non-complexed silybin (13% versus
2%, over 24 hours).
Some portion of the phytosomal
silybin remains in the liver for at least 24 hours.
Silybin entering the body as phytosomes also
clears the body via the kidneys. It appears in the urine
within a few hours and continues to clear via the urine
for up to three days.
Human Studies
Silybin in phytosome form is also well ab-
sorbed in humans.
Pharmacokinetic studies con-
ducted with human subjects showed a pattern similar
to rats. In the early studies (1990), eight healthy vol-
unteers ages 16-26 took single 360-mg oral doses of
silybin, either as phytosomes or non-complexed sily-
The silybin from silymarin rose slightly in the
plasma beginning one hour after dosing, and declined
to minimal levels by eight hours (Figure 5, open cir-
cles). Silybin phytosome was substantially present in
the plasma by one hour, peaked around two hours,
and at eight hours was almost three times the level of
silybin from silymarin (Figure 5, closed circles). By
measuring the total area under the curve (AUC) for
Figure 4. Relative Percentages of Silybin
Recovered in the Urine after Dosing with
Phytosomal Silybin or with Silybin from
Silymarin in Rats
% Dose
Non-phytosome Silybin
Figure 5. Plasma Silybin Uptake in Healthy
0 1 2 4
6 8
0 1 2 3 4
8 12
Plasma Silybin (ng/mL)
Closed circles: Silybin taken as phytosomes
Open circles: Silybin taken as silymarin
Inset: The very high level of silybin absorption
as phytosome in one subject
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Alternative Medicine Review u Volume 10, Number 3 u 2005 Page 197
each line, it was determined that phytosomal silybin
was absorbed 4.6 times better than the non-phyto-
some silybin from silymarin.
This compares with an
estimated 6.0-6.3 times better bioavailability in rats,
as calculated from plasma uptake patterns
and bile
There was substantial variability among
subjects, as reected by the broad error bars in Figure
5; one subject had extremely high absorption (see the
inset, Figure 5).
A further, multiple-dose study was conducted
with these same healthy young volunteers.
In place
of a single dose of 360 mg, phytosomal silybin was
given twice daily (120 mg every 12 hours, totaling
240 mg silybin daily) for eight days. This dosing pat-
tern maintained the same high plasma concentrations
and high total absorption attained by the single higher
dose (360 mg) given for one day. There was no de-
cline in absorption efciency after multiple days of
As conrmed for rats, in the human subjects
silybin coming from phytosomes does reach the in-
tended target organ, the liver. This was proven using
nine volunteer patients who had earlier undergone
surgical gall bladder removal necessitated by gall-
They were already “rigged” for such a
study, with bile drained via a tube. They were given
single oral doses of 120 mg silybin as silybin phyto-
some (Siliphos) or silymarin, and bile was monitored
for silybin levels. Silybin appeared in the bile and
peaked after four hours. In the case of phytosomal
silybin, the total amount recovered in the bile after
48 hours accounted for 11 percent of the total dose.
In the case of silymarin, approximately three percent
of the silybin was recovered. These data suggest a
four-times greater passage through the liver for phy-
tosomal silybin. Also, the human bile data
favorably with the human AUC data, which suggest a
4.6-times greater bioavailability from the phytosome
form than the simple extract.
A 1998 study suggests Siliphos may be more
bioavailable when taken as a liquid in softgel form.
Twelve healthy subjects were given a single dose of
80 mg silybin as phytosomes, either in softgel or two-
piece hardgel capsules, then had blood samples taken
for eight hours. Subsequently, they were crossed-over
to the opposite product and sampled again. The maxi-
mum plasma concentration attained from the softgel
was three times greater than from the hardgel. Aver-
age AUC after the rst hour for the softgel was more
than twice that for the hardgel cap, suggesting faster
absorption as well.
Clinical Efcacy of Silybin Phytosome
Findings from several studies with human
subjects indicate that silybin taken by mouth as Sili-
phos has markedly greater benet, milligram for mil-
ligram, than does non-complexed silybin from sily-
In 1991, Marena and Lampertico reported
on several studies involving a total of 232 patients
with liver disorders treated with phytosomal sily-
Daily intakes ranged from 240-360 mg silybin
in phytosome form, taken for up to 150 days between
meals. Control subjects were also treated with either
non-complexed silybin (n=49) or with placebo or no
treatment (n=117). Evaluation of efcacy was based
primarily on serum liver enzyme levels, namely as-
partate aminotransferase (AST), alanine aminotrans-
ferase (ALT), and gamma-glutamyltranspeptidase
(GGT). The investigators came to the conclusion that
phytosomal silybin had “signicant clinical effect.”
In the population of patients with alcoholic hepatitis,
serum AST and ALT returned to normal signicantly
faster with Siliphos than with the reference prepara-
tion of non-phytosomal silybin. In another study, pa-
tients with acute viral hepatitis (A or B types) fared
better on the phytosomal preparation compared to
placebo-treated subjects. Similar ndings emerged
for the patients with hepatitis of undetermined cause
(so-called iatrogenic cases).
In 1992, researchers at the Universities of
Milan and Bari reported on a controlled study of
chronic persistent hepatitis.
The study recruited
only patients with biopsy-conrmed hepatitis. The
drug treatments available for this condition have lim-
ited efcacy, do not work at all for many patients, and
have major adverse effects. These patients were ran-
domized to receive either 240 mg silybin phytosome
(n=31) or placebo (n=34), one capsule orally, twice
daily for three months. The phytosome group expe-
rienced signicant lowering of both serum ALT and
AST, while in the placebo group both enzyme indica-
tors worsened. The silybin treatment was well toler-
ated, with even fewer adverse events reported than
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Page 198 Alternative Medicine Review u Volume 10, Number 3 u 2005
for the placebo group, and no patient discontinued the
trial due to adverse effects.
A short-term, 1993 pilot study, representing
a collaboration between Indena (a manufacturer of a
wide range of botanical extracts, including Siliphos)
and researchers at the University of Florence, exam-
ined the effect of silybin phytosome on 20 patients
with chronic active hepatitis (B and/or C).
this one-week trial, 10 patients received 480 mg si-
lybin daily and 10 received placebo. A reduction in
serum levels of ALT (29%), AST (25%), and GGT
(20%) was observed in the silybin group. Plasma lev-
els of silybin were markedly increased at day 7, at-
taining levels consistent with those measured in the
pharmacokinetic studies.
In the placebo group only
GGT showed a signicant decrease (8% compared to
20% in the silybin group).
This study also measured
serum malondialdehyde (MDA) levels, a byproduct
of lipid peroxidation. Although serum MDA fell in
the silybin group, it was not statistically signicant.
In another, very small pilot study, eight pa-
tients with chronic active hepatitis (B and/or C) were
treated with phytosomal silybin, at 240 mg silybin
for two months.
Liver enzymes ALT and AST were
signicantly reduced, while reductions in GGT and
MDA did not attain statistical signicance. As with
the patients in the previous study, baseline MDA lev-
els were very high when the study began. The nd-
ings from these two small pilot studies suggest that
phytosomal silybin is a valuable component of an in-
tegrated approach to managing active infection with
hepatitis B and/or C viruses. These ndings deserve
replication in larger and longer studies.
Data particularly useful in establishing dos-
ing recommendations came from a larger 1993 hepa-
titis trial at the University of Pavia involving 54 pa-
Patients with chronic hepatitis of either viral
or alcoholic origin were randomly assigned to one
of three groups. One group (n=19) received phyto-
somal silybin at 160 mg daily; another group (n=17)
received 240 mg daily; and the third group (n=18)
received 360 mg daily. The trial lasted two weeks,
with enzyme indicator testing done after weeks 1 and
2. Despite the short duration of the trial, AST was sig-
nicantly lowered by all dosages. At the two higher
doses of 240 and 360 mg daily (but not at 160 mg
daily) ALT and GGT were also signicantly lowered.
Furthermore, at the two higher doses a dose-effect re-
lationship was seen for AST and GGT (although not
for ALT) the higher the dose, the greater the de-
crease in liver enzymes. These differences were evi-
dent after one week. In this trial, four of 60 patients
experienced adverse effects and two dropped out of
the 360-mg group before the end of the rst week.
The researchers concluded that using phytosomal si-
lybin, an intake of 160 mg silybin daily (one 80-mg
capsule twice daily, taken between meals) provided
a good maintenance intake. They suggested that for
better and more reliable results the 240-mg daily in-
take might be appropriate. For more difcult cases
the 360-mg intake of phytosomal silybin might be
indicated, although there is greater possibility of ad-
verse effects.
A small, double-blind trial, published only in
abstract form, suggested phytosomal silybin might be
useful against hepatitis C in chronically infected pa-
tients who did not benet from interferon treatment.
Ten patients who had failed to measurably respond to
recombinant interferon alpha 2b (3 million units three
times weekly for six months) were studied according
to a crossover, randomized, double-blind trial design.
After 6-12 months of interferon withdrawal, patients
were randomly assigned to receive either phytosom-
al silybin (360 mg silybin daily) or placebo for two
months. After a one-month washout period subjects
were crossed over to the other treatment. After sta-
tistical analysis, the phytosomal silybin was found to
signicantly lower both ALT and AST, while the pla-
cebo failed to do so.
Phytosomal silybin is likely safe for cirrhotic
patients. Researchers at the University of Padua col-
laborated with Indena to study uptake of silybin phy-
tosome in 10 patients with compensated liver cirrho-
sis (Child’s Grade A).
The patients rst received a
single daily dose of 120 mg silybin phytosome, and
blood silybin levels were monitored. This was fol-
lowed by a multiple dose study in which patients re-
ceived a 120-mg dose twice daily for eight days. The
patients were found to absorb the silybin phytosome
as well as healthy subjects, although there was great
variability from patient to patient.
In this study, the prole of data from the
eight-day dosing period did not show signicant dif-
ferences from the rst day’s data.
From this nding
the researchers concluded that (on average) patients
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Alternative Medicine Review u Volume 10, Number 3 u 2005 Page 199
were not accumulating silybin in poorly functioning
livers, nor were any clinically adverse effects report-
ed. Such short-term experience does not prove the
supplement is safe for long-term use by a liver-com-
promised population. Another study by this group on
cirrhotic patients (n=9) used a higher dose of silybin
as phytosome (360 mg) for one day.
Great inter-pa-
tient variability was found, with no clinically adverse
effects. Since hepatitis patients can develop adverse
effects at this high intake,
such short-term experi-
ence does not prove the supplement is safe for long-
term use by patients with cirrhosis.
Animal Studies on
complex has been shown to
offer liver protection in labo-
ratory rats. Rats fed the toxic
solvent carbon tetrachloride
or the potentially liver-toxic
acetaminophen developed
abnormally elevated levels
of AST and ALT. When high-
dose silybin (as Siliphos) was
administered along with the
toxic insult, the liver enzymes
were signicantly reduced
(Figure 6).
Protective effects of
phytosomal silybin were ob-
served using rats pre-exposed
to toxins such as praseo-
dymium, galactosamine, and
the mushroom poisons phal-
loidin and alpha-amanitin.
This correlates with decades
of clinical observations that
silybin improves survival of
humans exposed to deathcap
mushroom (Amanita sp.) and
other toxic mushrooms.
Correlating with the
human trial ndings that sily-
bin protects the liver against
alcohol toxicity,
blocked some adverse effects
of ethanol in animal studies.
For example, ethanol fed to
rats in high doses raises liver
triglyceride (TG) levels. High TG levels are a proven
risk factor for cardiovascular disease in humans. One
study showed high-dose Siliphos fed to rats along
with ethanol signicantly blocked ethanol’s TG-el-
evating effect (Figure 7).
Figure 6. Silybin as Siliphos® Partially Protects against Experimental
Liver Damage from Carbon Tetrachloride (top panel) or Acetaminophen
(bottom panel)
250 mg/kg p.o. x 3
(as silybin)
250 mg/kg p.o. x 3
400 mg/kg p.o. x 3
-induced liver damage
-induced liver damage
Liver damage was monitored as blood levels of the standard
indicator enzymes AST and ALT.
Acetaminophen Siliphos®
400 mg/kg p.o.
(as silybin)
400 mg/kg p.o.
640 mg/kg p.o.
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Page 200 Alternative Medicine Review u Volume 10, Number 3 u 2005
In vitro Studies
Silybin’s potent
antioxidant activity is
thought to account for
much of its liver protec-
tion. One accepted ex-
perimental system for
generating free radicals
and calibrating antioxi-
dants is the NADPH/iron
effect on membranes
prepared from rat liver
cells. In this system, iron
pulls electrons from the
electron-rich NADPH
molecule and the resul-
tant molecules are used
to peroxidize cell mem-
branes. The main end-product of the membrane
breakdown is MDA. Silybin added to this “test tube”
system can block the formation of MDA
(Figure 8).
The silybin effect in blocking
MDA is dose-dependent, with increas-
ing concentrations of silybin having pro-
gressively greater blocking effect. Such
dose-dependency makes the effect more
relevant to the intact body. In liver pa-
renchymal cells isolated from rats, sily-
bin used in phytosome form entered the
cells and protected against MDA forma-
tion from a variety of peroxidative toxins,
including ADP/iron, cumene hydroper-
oxide, allyl alcohol, and bromotrichloro-
Similar protection against per-
oxidation was observed in rats pretreated
with the silybin-PC complex prior to the
cells being isolated. Other research con-
rms silybin can actually trap free radi-
cals within the membranes of liver cells,
as such reactive molecular fragments are
being generated from carbon tetrachloride
and methylhydrazine.
Figure 7. Phytosomal Silybin Partially Protects against Alcohol-induced
Increase of Liver Triglycerides
Ethanol Siliphos®
200 mg/kg p.o. x 5
(as silybin)
200 mg/kg p.o. x 5
mg triglycerides/100 g liver
Ethanol-induced liver damage
Figure 8. In vitro, Silybin Protects Rat Hepatocyte Membranes
from Free Radical Peroxidative Attack
µmoles MDA / mg protein
0 10 20 min
0.5 µM silybin
2.0 µM silybin
5.0 µM silybin
Note the dose-dependent, increased protection from
increasing concentrations of silybin.
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Safety and Tolerability of Silybin-PC
This phytosomal form of silybin has been
studied for safety.
Overall, it is well tolerated in
humans. According to researchers Marena and Lam-
healthy volunteers (total number not dis-
closed) received 360 mg silybin-phytosome complex
three times daily for three weeks without adverse
effect. They also reported treating 232 patients with
“liver disorders” for up to four months with either
240 or 360 mg daily, concluding that the tolerability
of the silybin-PC preparation was excellent. Minor
adverse effects (nausea, heartburn, dyspepsia, tran-
sient headache) were reported in 12 patients (5.2%
of the total studied), compared with 8.2 percent of
patients who received non-complexed silybin and 5.1
percent of patients on placebo. The phytosomal sily-
bin produced no clinically relevant blood changes in
these patients.
Phytosomal silybin has also proven safe in
traditional toxicological tests. Oral acute toxicity is
>5,000 mg per kg in rats, dogs, and monkeys. After
13-week, subacute toxicity studies, the preparation
was found safe for rats and monkeys at oral doses up
to 2,000 mg per kg per day. In 26-week chronic toxic-
ity studies, oral doses up to 1,000 mg per kg per day
were well tolerated in rats and dogs. In another 26-
week oral toxicity study, rats were fed a daily 2,000
mg per kg dose of Siliphos, equivalent to 160 g daily
for a 176-pound (80 kg) human. As published by In-
dena, body weight, liver weight, and enzyme indica-
tors of liver damage (AST, ALT) remained within the
normal, healthy range of the untreated control rats.
Pharmacological studies in mice, rats, and dogs in-
dicate phytosomal silybin does not adversely affect
central nervous system, cardiovascular, or respiratory
functions, and does not inuence stomach emptying
or intestinal motility, at oral doses as high as 1,000
mg per kg. The silybin-PC complex had no evident
adverse effects on reproduction in rats, and showed
no mutagenic effects in several test systems.
Conclusion and Future Research
Silybin-PC complexed as a phytosome pro-
vides signicant liver protection and enhanced bio-
availability over conventional silymarin when taken
orally. Phytosomal silybin is more rapidly absorbed
than silymarin, perhaps more so when taken in soft-
gels. It is also absorbed at least four times more com-
pletely than silymarin, reaching the liver rapidly and
appearing in the bile within a few hours. While sily-
marin must be taken at doses of approximately 420
mg daily to achieve benet, phytosomal silybin (Sili-
phos) can produce benet at intakes as low as 120 mg
daily, but can be safely administered at doses of 240-
360 mg daily. Since adverse effects are possible at the
higher intakes, monitoring would seem prudent for
subjects having ongoing intakes above 240 mg daily.
In addition to direct hepatoprotective effects,
silybin has iron-chelating capacity that could be in-
vestigated for management of chronic iron overload.
It is also under active investigation for cancer preven-
tion and management,
and has entered a Phase I
clinical trial for treatment of prostate cancer.
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... Due to low solubility in water, silibinin has a deficiency in absorption into the cell. These complications cause low bioavailability and poor cellular uptake of the drug (16). Nowadays, different nanocarriers with individual features are applied, such as liposomes (17), dendrimers (18), micelles (19), nanoemulsions (20), and polymersomes (21). ...
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Background: Colorectal Cancer (CRC) is the most common malignant gastrointestinal cancer. Cancer stem cells (CSCs) are the major cause of cancer recurrence and cancer drug resistance. Silibinin, as an herbal compound, has anticancer properties. Objectives: The present study aimed to evaluate the antiproliferative effects of silibinin on HT29 stem-like cells (spheroids). Methods: In this study, antiproliferative and apoptotic properties of Silibinin encapsulated in Polymersome Nanoparticles (SPNs) were evaluated by MTT assay, propidium iodide (PI) /AnnexinV assay, cell cycle analysis, and DAPI (4',6-diamidino-2-phenylindole) staining. The expression of some miRNAs and their potential targets was evaluated by real-time reverse transcription-polymerase chain reaction (qRT-PCR). Results: IC50 of SPNs was determined at 28.13±0.78µg/ml after 24 h. SPNs (28µg/ml) induced apoptosis by 32.36% in HT29 cells after 24 h. DAPI staining indicated a decrease in stained nuclei after SPNs induction. SPNs treatment increased the expression of miR-34a, as well as P53, BAX, CASP9, CASP3, and CASP8. The downregulation of miR-221 and miR-222 was observed in SPNs treated cells. Moreover, SPNs decrease the expression level of CD markers in HT29 spheroids (cancer stem cells) compared to untreated spheroids. Spheroids were completely destroyed after 72 h treatment with SPNs (28µg/ml). Conclusion: As evidenced by the obtained results, SPNs can be used as an effective anticancer agent in multi-layer (cancer stem cells) and mono-layer cancerous cells with the upregulation of tumor suppressive miRs and genes, as well as downregulation of oncomiRs and oncogenes.
... [7] Phytosomes are the one of the promising, particulate drug delivery system that is used for novel/ Targeted Drug Delivery Systems (NDDS/ TDDS). [8] Phytosome is an advanced ways to deliver the water soluble phytoconstituents or herbal extracts either complexed with phospholipids (flavonoid/ terpenoid based compounds in herbal extracts binds with phosphatidylcholine) or surrounded by phospholipids that shows better pharmacokinetic and pharmacodynamic profile as an improved absorption and bioavailability of phytoconstituents, specially poly-phenolics. [9] Phytosome is a complex of phospholipid with herbal molecules formed by molecular-level association. ...
... This physiochemical property change is due to the formation and confirmation of a true stable phytosome based complex. [10] Advantages of phytosomes Phytosomes have the following advantages [12] [13] [14] 1. Improves the absorption of lipid insoluble polar phytoconstituents by oral route, topical/dermal shows improving bioavailability of herbal constituents and its formulations. ...
From the traditional time onwards it has been attempt of the physician and the apothecary to provide patients with the best possible forms of medicines so that recovery from disease is faster and complete of the Treatment regimen. The drugs are designed and delivered in a suitable desired form of formulations keeping in view of patient's safety, efficacy and acceptability A comprehensive review on various Novel Drug Delivery Systems and their challenges in designing of Herbal drug Section A-Research paper 1310 Eur. Chem. Bull. 2023, 12(Special Issue 6), 1309-1337 among other biological factors like bioavailability, to avoid drug incompatibility, drug resistance etc. With the continues progress in all spheres of science and technology in the segment of pharmaceutical field, the dosage forms have evolved from simple dosage form like mixtures and pills to highly sophisticated technology like intensive drug delivery systems, which are pharmaceutically known as Novel Drug Delivery Systems (NDDS). The present study elaborately review the various Novel delivery systems like Phytosome, Liposomes, Nanoparticles, Niosomes, Proniosomes, Self emulsifyed drug delivery systems (SEDDS), Transdermal Drug Delivery System, Microspheres, Ethosomes, Transfereosomes, , Self nano emulsifyed drug delivery systems (SNEDDSs), Dendrimers and its applications in design and delivery of herbal formulations to improve the safety and efficacy .Also the review elaborated the retrospective research on novel drug formulations with herbs in various segments like
... The flavonoid and therefore the terpenoid components of the herbal extract are ready to directly bind with phosphatidylcholine moiety hence they're widely prepared. [4,5,6] Fig. 1: Structure of Phytosome. [7] Principle of Phytosome Technology The flavonoid and terpenoid constituent of plant extracts lend themselves suitable for direct binding to phosphatidylcholine. Phytosomes are composed by the reaction of a stoichiometric amount of the phospholipid (phosphatidylcholine) with the standardized extract or polyphenolic constituents (like simple flavonoids) in a non-polar solvent. ...
Full-text available
During the last centuries, chemical and pharmacological studies have been performed on a lot of plant extracts to know their chemical composition and confirm the indications of traditional medicine. Phytosome plays an important role to facilitate absorption and improve bioavailability which include standardized plant extracts or water soluble phyto-constituents into phospholipids to provide lipid conformable molecular complexes. Phytosomes is a novel formulation technology which helps to overcome these problems. The term ‘phyto’ means plant while ‘some’ means cell-like. Phytosome is composed of phospholipids, mainly phosphatidylcholine, producing a lipid compatible molecular complex with other constituents. Phytosomes are more potent as compared to conventional herbal extracts owing to their enhanced capacity to cross the biological membrane and finally reaching the systemic circulation. They have anti-inflammatory, anti-oxidant, anticancer, anti-diabetic, hepato-protective properties. Phytosome has been an emerging trend in delivery of herbal drugs and nutraceuticals. This paper provides the detailed information about the preparation, advantages, characterization and evaluation of phytosomes. This review highlights information of commercial products of phytosomes as well as research on novel approaches for phytosomes drug delivery.
... It is being increasingly recognized that many of these phytonutrients need to be in emulsion system to make them more bioavailable [1]. Bioactives like phytosterols, carotenoids and phenolics need an emulsion vehicle to diffuse in the aqueous system of the gut lumen, and cross the lipid membrane of the absorptive intestinal mucosal cells [2,3]. ...
... Plant tissues contain some water-soluble flavonoids that can be converted into lipid-compatible molecular complexes called phytosomes, which follow the same absorption pathway as lipid-soluble phytochemicals like carotenoids (Kidd and Head, 2005). Liu et al. (2016) observed that some phenolic compounds are micellarized during mango digestion, showing bioaccessibility values 1.5 times higher than those of carotenoids. ...
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The mango fruit is of great economic value worldwide and of great nutritional importance. Its functional effects are due to numerous important nutrients and bioactive compounds. In this review, the benefits of mango fruit (pulp, peel, and seed) for human nutrition and health are detailed. The first part of the review presents the nutrient and phytochemical content of the mango fruit, and the second part addresses its health effects. The very diverse phytochemical components in mango fruit can be classified into several groups including macronutrients such as carbohydrates (sugars, pectin, and cellulose), proteins, lipids (Ω-3 and Ω-6 fatty acids); micronutrients such as vitamins A and C, minerals, pigments (chlorophylls, carotenoids, and anthocyanins, depending on the cultivar), phenolic compounds (phenolic acids and flavonoids), and volatile compounds. The beneficial effects of mango fruit and its components have been studied on different non-communicable diseases such as obesity, type 2 diabetes mellitus, hypertension, and cancer. A great diversity of research approaches have been used to study mango fruit health benefits, and those can be grouped into three main categories: a) those that present the associations or direct effects of the edible portion of the fruit on health through observational epidemiological studies and clinical trials; b) in vivo and in vitro experimental approaches that address either the physiological effects or mechanisms of several kinds of extracts or purified components of mango fruit (pulp, peel and seed), and c) preclinical and clinical studies that explore the possible pharmacological uses of mango fruit. Current scientific understanding of mango health benefits suggest that consumption of mango fruit and its byproducts containing bioactive components can be useful as part of a healthy diet in order to reduce the incidence of health problems.
The research was done to examine the impact of dietary silymarin on growth performance, total tract digestibility, faecal microbial, faecal gas emission and absorption rate in blood of growing pigs. Experiment 1: a total of 140 growing pigs (24.47 ± 2.49 kg) were used in a 6-week trial. There were four dietary treatment groups (seven replicate pens/treatment, five pigs/pen) and treatment diets composed of corn, soybean meal (SBM), distillers dried grains with solubles (DDGS), and rapeseed meal-based basal diets with 0%, 0.025%, 0.050% and 0.10% of micelle silymarin respectively. Experiment 2: A total of 18 pigs were divided into six treatment groups. Treatment diets: TRT1, TRT2 and TRT3 were basal diets with 30, 150 and 300 g powdered silymarin respectively; and TRT4, TRT5 and TRT6 were basal diets with 30, 150 and 300 g micelle-type silymarin respectively. Average daily gain (ADG) tended to increase (p < 0.10) at Week 3 and overall experiment after silymarin addition. Overall ADG and average daily feed intake are also intended to improve (p < 0.10) linearly in this study. During Week 6, growing pigs fed silymarin showed linearly increased (p < 0.05) apparent total tract digestibility (ATTD) of dry matter, nitrogen and energy. Dietary silymarin supplementation increased (p < 0.10) linearly the faecal Lactobacillus count at Week 3 while Escherichia coli count was linearly decreased at both the 3rd week (p < 0.05) and 6th week (p < 0.10). Silymarin supplementation showed no effect on faecal gas emissions. A higher (p < 0.05) absorption rate in the blood was found in micelle-type silymarin compared to powdered silymarin after the 1st, 2nd, 4th, 8th, 12th and 24th h of feeding. Results suggest that silymarin in a corn-SBM-DDGS-rapeseed meal-based diet may help to improve ADG, FI, ATTD and faecal microflora in growing pigs. And absorption rate in the blood of pig is higher in micelle-type silymarin.
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Phosphatidylcholine (PC) is one of the most important support nutrients for the liver. PC is a phospholipid, a large biological molecule that is a universal building block for cell membranes. A cell's membranes are its essence: they regulate the vast majority of the activities that make up life. Most liver metabolism occurs on cell membranes, which occupy about 33,000 square meters in the human. More than 2 decades of clinical trials indicate that PC protects the liver against damage from alcoholism, pharmaceuticals, pollutant substances, viruses, and other toxic influences, most of which operate by damaging cell membranes. The human liver is confronted with tens of thousands of exogenous substances. The metabolism of these xenobiotics can result in the liver's detoxicative enzymes producing reactive metabolites that attack the liver tissue. Dietary supplementation with PC (a minimum 800 mg daily, with meals) significantly speeds recovery of the liver. PC has also been shown to be effective against alcohol's liver toxicity in well-controlled studies on baboons. PC has other qualities that enhance its usefulness as a dietary supplement. PC is safe, and is a safer means for dietary choline repletion than choline itself. PC is fully compatible with pharmaceuticals, and with other nutrients. PC is also highly bioavailable (about 90% of the administered amount is absorbed over 24 hours), and PC is an excellent emulsifier that enhances the bioavailability of nutrients with which it is coadministered. PC's diverse benefits and proven safety indicate that it is a premier liver nutrient.
Eight patients (two men and six women; mean age, 54.6 + 5 years) with viral chronic active hepatitis were treated with silipide (IdB1016), a new silybin-phosphatidylcholine complex, for 2 months. After treatment with IdB1016, serum malondialdehyde levels decreased by 36%, and the quantitative liver function evaluation, as expressed by galactose elimination capacity, increased by 15%. A statistically significant reduction (P < 0.05) of transaminases was also seen. These results suggest that silipide may be effective in improving the biochemical and quantitative indices of hepatic function in patients with chronic active hepatitis.
Silybin, a natural occurring flavolignan isolated from the fruits of Silibum marianum, has been reported to exert antioxidant and free radical scavenging abilities. It was suggested to act also as an iron chelator. The complexation and protonation equilibria of the ferric complex of this compound have been studied by potentiometric, spectrophotometric and electrochemical techniques. The formation of the complex silybin–Ga(III) in anhydrous DMSO-d6 has been studied by 1H NMR spectroscopy. Mass spectrometry and infrared spectroscopy on silybin–Fe(III) complex confirm all data obtained by 1H NMR spectroscopy. The experimental results show that silybin binds Fe(III) even at acidic pH. Different ternary complexes were observed at increasing methoxide ion concentration and their stability constants have been calculated. The results show the possible role of silybin in relation to the chelation therapy of chronic iron overload, as occurs in the treatment of Cooley’s anemia.