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Abstract

The artichoke, Cynara scolymus, is one of the most ancient plants grown in the world, and its extracts, obtained from different parts of the plant (leaves, fruits and roots), have been used as medicaments from time immemorial. The pharmacological and therapeutic effects of the artichoke on the liver had already been well known in the 17th century. Modern studies started in the last century confirmed the stimulating properties of artichoke extracts on the liver and gallbladder. The ensuing wave of research was initially focused on the patent liver-stimulating, diuretic and choleretic effects exerted by artichoke preparations on both animals and man, then discovering such other therapeutic properties as the hypolipemizing activity, antioxidant activity and hypoglycemizing activity. This review enumerates the most significant studies that have highlighted these therapeutic properties. Complementary medicine information needs to be incorporated into clinical practice and patient and professional education, in addition to adequate education about proper nutrition. Awareness of the widespread use of complementary and alternative medicine by people with metabolic disorders is crucial for healthcare professionals in order to prevent cardiovascular disease.
Monaldi Arch Chest Dis
2013; 80: 17-26
REVIEWS
Introduction
Cynara scolymus extracts obtained from differ-
ent parts of the plant (leaves, fruits and roots) have
been used as medicaments since ancient times [1-3].
Traditional medicine made use of the artichoke a
choleretic, diuretic, laxative, appetite-stimulant,
anti-gout medication and depurative [4]. The inter-
est in the artichoke as a medicament was lost around
the mid-19
th
century, however, and was then revived
again in the first half of the 20
th
century, when
French scientists had described artichokes as poten-
tial drugs against liver disorders. In the 1960s, one
of the active ingredients found in the artichoke –
called cynarin – was identified and successfully
marketed as a liver-protecting agent. In a short time,
this active ingredient was isolated, and some Italian
researchers identified its chemical structure, thus en-
abling its synthesis. Some cynarin-based synthetic
preparations were used to treat liver and gallbladder
disorders, as well as to reduce lipid and cholesterol
values, even if, over the years, they were then re-
placed by drugs that were more specific for these
diseases. In the last ten years, however, the aqueous
extract from artichoke leaves has regained an ac-
knowledged medical value in Germany: it has been
officially certified as safe and effective if it is ob-
tained through a process complying with the rele-
vant international pharmaceutical regulations. The
extract has been used as a dietary supplement indi-
cated for treatment of hyperlipidemia [5, 6]. In addi-
tion, Pharmacopoeias have approved its use as a he-
patic stimulant and appetite stimulant, particularly
in children [7-10]. Artichoke leaves, whether fresh
or dry, are presently included in the official Euro-
pean monographs on herbal products, and the plant
is mentioned in the most important collections of
medicinal herbs and phytotherapy and general phar-
macognosy books [11-15], which approve use of ar-
tichoke as a choleretic, diuretic, hepatoprotective
and liver-stimulating substance. As far as Italy is
concerned, the artichoke is mentioned in the Italian
Health-promoting properties of artichoke
in preventing cardiovascular disease by its
lipidic and glycemic-reducing action
Proprietà di promozione sulla salute del carciofo mediante
prevenzione delle malattie cardiovascolari grazie alla sua
azione ipolipodemizzante ed ipoglicemizzante
Mariangela Rondanelli, Francesca Monteferrario, Simone Perna,
Milena Anna Faliva, Annalisa Opizzi
Department of Applied Health Sciences, Section of Human Nutrition and Dietetics, Faculty of Medicine, Azienda di Servizi alla
Persona di Pavia, University of Pavia.
Corresponding author: Mariangela Rondanelli; Department of Applied Health Sciences, Section of Human Nutrition and Dietetics,
Faculty of Medicine, Azienda di Servizi alla Persona di Pavia, University of Pavia, Istituto di Cura “Santa Margherita”, Via Emilia 32,
I-27100 Pavia, Italy; Tel. International +39-0382-381749, + 39- 3382559239, Fax International +39-0382-381218; E-mail address:
mariangela.rondanelli@unipv.it
ABSTRACT: Health-promoting properties of artichoke in
preventing cardiovascular disease by its lipidic and glycemic-
reducing action. M. Rondanelli, F. Monteferrario, S. Perna,
M.A Faliva, A. Opizzi.
The artichoke, Cynara scolymus, is one of the most an-
cient plants grown in the world, and its extracts, obtained
from different parts of the plant (leaves, fruits and roots),
have been used as medicaments from time immemorial. The
pharmacological and therapeutic effects of the artichoke on
the liver had already been well known in the 17
th
century.
Modern studies started in the last century confirmed the
stimulating properties of artichoke extracts on the liver and
gallbladder. The ensuing wave of research was initially fo-
cused on the patent liver-stimulating, diuretic and choleretic
effects exerted by artichoke preparations on both animals
and man, then discovering such other therapeutic properties
as the hypolipemizing activity, antioxidant activity and hy-
poglycemizing activity. This review enumerates the most
significant studies that have highlighted these therapeutic
properties. Complementary medicine information needs to
be incorporated into clinical practice and patient and pro-
fessional education, in addition to adequate education about
proper nutrition. Awareness of the widespread use of com-
plementary and alternative medicine by people with meta-
bolic disorders is crucial for healthcare professionals in or-
der to prevent cardiovascular disease.
Keywords: artichoke, caffeic acid derivatives, Cynara
scolimus, cholesterol, flavonoids, glycemia.
Monaldi Arch Chest Dis 2013; 80: 17-26.
Pharmacopoeia X Edition [9] as a dry nebulization
extract titrated with caffeoylquinic acids calculated
as chlorogenic acid min. 13% and max. 18%.
Complementary medicine information needs to
be incorporated into clinical practice and patient and
professional education, in addition to adequate edu-
cation about proper nutrition [16]. Awareness of the
widespread use of complementary and alternative
medicine by people with metabolic disorders is cru-
cial for healthcare professionals in order to prevent
cardiovascular disease [17].
Chemistry of the biologically active molecules
found in the artichoke
From a chemical point of view, artichoke leaves
contain different molecules with important pharma-
cological activities: caffeic acid derivatives,
flavonoids, sesquiterpenic lactones, anthocyans, in
particular cyanidin and tannins, volatile oils, includ-
ing terpenoids, carotenoids, saturated, unsaturated
and polyunsaturated fatty acids, including linoleic,
palmitic, oleic and stearic acids, other unsaturated
compounds, like hydroxymethyl acrylic acid and
polyacetylene, citric, malic, lactic, succinic and
glycemic acids, monosaccharides, oligosaccharides
and polysaccharides of different kinds, such as, for
example, various sugars, mucilages, pectins, inulin,
amino acids and proteins, like L-asparagine, and a
large number of enzymes, including oxidase, perox-
idase, cynarase, ascorbinase, protease, ashes, potas-
sium, magnesium, calcium and traces of other met-
als.
Caffeic acid derivatives
Many of the pharmacological activities of arti-
choke leaf extracts were attributed – at least initially
– to the presence of caffeoylquinic acids (CQS). [18-
20]. In literature, these compounds are also called,
more generically, “caffeic acid derivatives” or “orto-
dihydrophenols”; they are synthetically obtained
from the condensation of a quinic acid molecule
with one or two caffeic acid molecules.
Historically, chemical investigations on these
component began in 1840, when a certain Mr. Grit-
teau isolated a substance that is known today as cy-
narin. The true nature of this substance was discov-
ered by Chabrol [21] and his collaborators in 1931.
Studies on the chemical nature of cynarin developed
over the years, and in 1965 some Authors [22]
demonstrated that this substance actually corre-
sponded to 1,5- dicaffeoylquinic acid. Today cy-
narin can also be obtained through an easy and
cheap semi-synthesis method that does not require
use of any chromatographic step [23]. This proce-
dure is based on the separation of the fraction rich in
1,5-dicaffeoylquinic acid, the isomerization of the
compound and, owing to its higher polarity, on the
simple isolation of cynarin from the reaction mix. In
addition to cynarin, other monocaffeoylquinic acids
have also been isolated from artichoke leaves:
chlorogenic acid (or 5-O-caffeoylquinic acid) and
crypto-chlorogenic acid (or 4-O- caffeoylquinic
acid) [24, 25].
The highest content in caffeoylquinic acids can
be found in the leaf at the end of the first vegetation
year [26]. But these acids can also be found in small
quantities in all the other parts of the plant. Pharma-
cologically, these compounds have exhibited
choleretic effects (that is, they stimulate the biliary
flow) and, in part, a cholesterol-reducing action.
Flavonoids
The chief flavonoids identified in leaves (0.1 to
1%) are luteolin [27-30] and three luteolin glyco-
sides: cynaroside (luteolin-7-O-glucopiranoside),
scolymoside (luteolin-7-O-rutinoside), and cy-
narotrioside (luteolin-7-O-rutinosil-4-O-glucopira-
noside). In addition, recent analyses also highlighted
the presence of rutin, apigenin, quercetin and other
flavonoids together with luteolin and its glycosides
[31, 32]. It now seems to have been ascertained that
these compounds – in particular luteolin – seem to
exert a pharmacological effect on cholesterolemia
through at least two different mechanisms: on the
one hand they modulate cholesterol absorption and,
on the other, they slow down endogenous choles-
terol synthesis by inhibiting HMG-CoA-reductase
synthesis. In addition, these substances can also en-
hance the production of biliary acids and exhibit a
marked antioxidant activity in the liver and serum.
Sesquiterpenic lactones
In addition to flavonoids and caffeoylquinic acid
derivatives, artichoke leaves also contain a number
of sesquiterpenic lactones (cynarotriol, cynaropi-
crin), which are responsible for the typical bitter
taste of the artichoke [27, 33]. The highest contents
in these substances were measured in young leaves
immediately after flowering; on the contrary, they
are absent in roots, ripe fruits and flowers. These
components are endowed with hypocholesterolem-
izing antiinflammatory activity.
Other components
Other components found in the artichoke in-
clude: anthocians, and in particular cyanidin and
tannins [34]; more than 30 volatile oils, including
terpenoids [35], carotenoids [36]; saturated, unsatu-
rated and polyunsaturated fatty acids, including
linoleic, palmitic, oleic and stearic acids [37]; other
unsaturated compounds, such as hydroxymethyl
acrylic acid and polyacetylene [38]; citric, malic,
lactic, succinic and glycemic acids [39]; monosac-
charides, oligosaccharides and polysaccharides of
different kinds, such as, for example, various sugars,
mucilages, pectins, inulin [40, 41]; amino acids and
proteins, like L-asparagine, and a large number of
enzymes [42], including oxidase, peroxidase, cy-
narase, ascorbinase, protease [43]; ashes, potassium,
magnesium, calcium and traces of other metals.
Pharmacology of the artichoke
The pharmacological and therapeutic character-
istics of cynarin and the other active ingredients
found in the artichoke leaves are described below
and schematically listed as follows: 1. Hypolipemic
and cholesterol biosynthesis-inhibiting properties. 2.
Antioxidant properties. 3. Hypoglycaemic proper-
ties. 4. Liver-protecting properties. 5. Choleretic
properties.
18
M. RONDANELLI ET AL.
1. Action on lipid metabolism
A large number of studies demonstrated that Arti-
choke extracts act on lipid metabolism by decreasing
production of cholesterol and endogenous triglycerides
and supporting their excretion or the natural re-distrib-
ution through the organism. They also strengthen bile
production by increasing the quantity of biliary acids
and cholesterol discharged with bile. Since bile is the
chief route to eliminate cholesterol, the stimulation of
biliary secretion by artichoke extracts results in causing
the physiological reduction of cholesterol in the liver
and serum. In literature, there are also a number of
studies highlighting a direct action of artichoke extracts
on the endogenous synthesis of cholesterol. A number
of reserchers investigated these activities closely
through both experimental and clinical settings. Del
Vecchio [44] had highlighted, in vitro, that the arti-
choke extract aided cholesterol esterification in serum,
while, together with this effect, Obrecht also observed
an action on atherosclerotic plaques. Preziosi and col-
leagues [45] tested the effects of an intravenous admin-
istration of cynarin and caffeic acid on serum choles-
terol of the rabbit. In these animals, significant results
were obtained following administration of doses of
over 100 mg/kg, and the reduction in cholesterol levels
lasted for more than 72 hours, with the maximum re-
duction occurring between the fourth and sixth hours
from administration [45, 46]. The action was more ef-
fective on esterified cholesterol rather than on free cho-
lesterol; the activity of caffeic acid was found to be
equivalent to that of cynarin, even if its duration was
shorter. The action of these two compounds seems to
be ascribable to inhibition of liver cholesterol biosyn-
thesis, rather than to the increase in serum cholesterol
solubilization or esterification power [47]. Gebhardt in-
vestigated the possible mechanisms of action of the dif-
ferent components of the artichoke cholesterol synthe-
sis inhibition [48]. An aqueous extract from artichoke
leaves was used in high doses to inhibit cholesterol
biosynthesis, in a dose-dependent manner, starting
from 14C-acetate in a culture of rat hepatocytes. The
failure in cholesterol synthesis seems to be linked to
some inhibition of HMG-CoA reductase by the arti-
choke extracts. This hypothesis was then compared
with the results obtained with mevastatin - an HMG-
CoA inhibitor. The comparison yielded similar results,
although the action of artichoke extracts lies in the
modulation of the activity of HMG-CoA reductase,
rather than in a true inhibition. The effects seem to be
induced chiefly by flavonoids, such as luteolin and cy-
naroside, and, to a lesser extent, by cynarin and caffeic
acid. These early studies were then followed by a con-
siderable number of investigations using both artichoke
extracts and cynarin alone, which demonstrated to pos-
sess good therapeutic efficacy in patients with normal
or high cholesterol and triglyceride levels in serum;
these results were then reviewed by Schilcher and Heil
in 1992, by Wegener [49] and Schmidt in 1995, by
Kraft [50] in 1997 and by Wegener and Fintelmann in
1999 [51]. The Table 1 and 2 provide an overview of
19
ARTICHOKE IN PREVENTING CVD: A REVIEW
Table 1. - Results of studies on the effects of cynarin and artichoke extracts on cholesterol serum from 1959 to 1994
(meta-analysis by Wegener and Schmidt).
Authors and Number Treatment Daily dose
Total Cholesterol (mg/dl)
publication year of patients length in weeks (mg)
From to Reduction %
Mancini et al. (1961) 23 8 1500 256 ± 40 192 ± 20 25
Caruzzo et al. (1969) 1 4 1000 n.a. Reduction Not available
Cairella and Volpari (1971) 24 4 1000 283 ± 7 247 ± 5 13
Hammerl et al. (1973) 132 52-80 60 310 214 31
Eberhardt (1973) 12/10 5 1500 234 ± 38 199 ± 54 15
Montini et al. (1975) 30/30 7 500 ca. 300 ca. 240 20
Pristautz (1975) 60 8.5 60 298 ± 6 266 ± 9 11
Heckers et al. (1977) 9 12 250 381 ± 31 375 ± 38 2
Adam and Kluthe (1979) 7 11 1000 275 ± 85 213 ± 53 23
Vorberg (1980) 50 4 1200 306 ± 50 260 ± 61 15
Wegener (1994) 170 6 1920 267 228 14.5
Wójcicki and Kadikow (1974) 20 3 500 (wk 1) 1085 ± 516 819 ± 179 25
450 (wk 2/3)
Wójcicki and Winter (1975) 10 4 900 203 ± 11 153 ± 11 25
Wójcicki et al. (1979) 43 4 750 293 ± 15 260 ± 12 11
Palacz et al. (1981) 43 52 900 Slight reduction
Wójcicki et al. (1981) 30 6 900 203 ± 6 179 ± 15 12
the results of the studies conducted to assess the effect
of the administration of the artichoke extract on lipid
metabolism in man.
It is impossible to draw any correlations among
the different results because of the lack of standardis-
ation of the methods and substances used in the stud-
ies. Nonetheless, all the studies, except one, demon-
strated statistically significant improvements in cho-
lesterol and triglycerides levels. As a matter of fact,
Heckers [52] administrated daily doses of 250 and
750 mg synthesis cynarin preparations for three
months in 17 outpatients affected by familial type IIa
or IIb hypercholesterolemia without observing any
significant improvements in cholesterol and triglyc-
erides levels, and came to the conclusion that cynarin
was relatively ineffective as a therapeutic regimen in
hyperlipemia. After the Polish investigator Wojcicki
and collaborators had conducted studies with cynarin
in the rat, they studied the influence of this com-
pound, and then of artichoke extracts, in men of dif-
ferent ages affected by primitive or secondary hyper-
cholesterolemia. First, they assessed the influence of
cynarin on serum lipid levels of 20 diabetic patients,
of 20 to 77 years of age, with clofibrate-resistant hy-
percholesterolemia [53]. Cynarin was administered
for 21 days: through i.m. injections (0.5 g/die) for the
first ten days and then through three tablets a day
(each containing 0.15 g cynarin) for the remaining
days. Both cholesterol and triglycerides decreased
considerably. Cynarin was then administered in pa-
tients affected by hypercholesterolemia alone. In this
case, the agent was administered through the intra-
venous route at a daily dose of 1 g for 21 days, and
then orally at a daily dose of 0.75 g for another 21
days. This study suggests that the hypocholes-
terolemizing action of cynarin could be enhanced by
treatment with higher doses and/or for longer periods
of time. Other investigations with cynarin [54] or ar-
tichoke extracts confirmed their beneficial effects in
patients affect by hyperlipemia. For example, the de-
crease in cholesterol, triglycerides (to –62% of the
baseline value), free fatty acids, phospholipids and
lipoproteins was observed in 30 healthy elderly indi-
viduals (aged 75 years on the average) following
daily administration of 0.45 or 0,9 g extract, contain-
ing 0.09% polyphenols, for six weeks. The adminis-
tration of different doses of two different artichoke
preparations for 27 or 45 weeks was compared in in-
dividuals with primary hypertriglyceridemia unaf-
fected by treatment with clofibrate; this study resulted
in the improvement of serum triglycerides levels in
39 out of 73 patients (58.5 %; mean value of the over-
all results), with the normalization of 12 cases
(16.8%). The fraction of phospholipids and free fatty
acids in blood was then assessed in 38 patients af-
fected by hypertriglyceridemia and treated with two
different doses of 0.25 g (no = 22) and 0.5 g (no = 16)
artichoke extract three times a day for 27 or 45 weeks.
Statistically significant improvements of cholesterol
in serum were observed after 45 weeks in the patients
treated with the higher dose (p <0.02). As far as phos-
pholipids were concerned, changes were observed
only in lecithin levels (p <0.02) in both treatment
groups; on the contrary, lysolecithin, sphyngomielin,
phosphatidylcholine, phosphatidylethanolamine,
lysophosphatidylethanolamine and cardiolipin levels
remained statistically unchanged. High LDL levels,
together with high cholesterol and triglycerides lev-
els, are a risk factor for various degenerative vascular
diseases, and in particular for arteriosclerosis. A mul-
ticentre, double-blind, randomised, placebo-con-
trolled clinical trial was published by Englisch and
collaborators in 2000 [55]. This trial analysed the ef-
ficacy and tolerability of an aqueous artichoke extract
with respect to hypercholesterolemia. The prepara-
tion was formulated in coated tablets containing 450
mg artichoke extract. The trial enrolled 143 adult pa-
tients (aged between 35 and 69 years) with total base-
line cholesterol levels higher than 280 mg/dl; they re-
ceived 1,800 mg artichoke extract or placebo a day
20
M. RONDANELLI ET AL.
Table 2. - Results of studies on the effects of cynarin and artichoke extracts on triglycerides serum from 1959 to 1994
(meta-analysis by Wegener and Schmidt).
Authors and Numebr Treatment Daily dose
Triglycerides (mg/dl)
publication year of patients length in weeks (mg)
from to Reduction %
Hammerl et al. 1973) 132 52-80 60 228 174 24
Mars and Brambilla 1974) 15/15 8.5 1000 237 ± 64 155 ± 47 35
Montini et al. 1975) 30/30 7 500 ca. 230 ca. 200 13
Pristautz 1975) 60 8.5 60 369 ± 11 303 ± 25 18
Vorberg 1980) 50 4 1200 196 ± 55 174 ± 80 11
Wójcicki and Kadikow 1974) 20 2 450 (wk 1) 704 ± 231 513 ± 177 27
500 (wk 2)
Wójcicki and Winter 1975) 10 4 900 143 ± 75 117 ± 43 18
Wójcicki et al. 1979) 43 4 750 547 ± 97 363 ± 43 33
Wójcicki et al. 1981) 30 6 900 135 ± 17 71 ± 8 47
Palacz et al. 1981) 43 52 900 – – 27.9
for more than 6 weeks and were forbidden to con-
sume such other medications as antibiotics or statins
during the experiment. Primary endpoints were cho-
lesterol and triglycerides levels in serum, and sec-
ondary endpoints were the values of liver enzymes.
The reductions in total cholesterol levels were ini-
tially comparable between the two groups, but after
the seconds week, the cholesterol level began to in-
crease in the group treated with placebo, while it de-
creased in the treated group. At the end of treatment,
the reduction in total cholesterol levels (-18.5% in
comparison with –8.6% in the placebo group) and
LDL cholesterol levels (-22.9% in comparison with
–6.3% in the placebo group) in the treated group was
statistically significant (p = 0.0011 and p = 0.0001, re-
spectively) in comparison with placebo. In the au-
thors’ opinion, these results are almost comparable to
those obtained with statins. The LDL/HDL ratio de-
creased by 20.2% in the treated group and by 7.2% in
the placebo group, although the HDL cholesterol lev-
els remained unchanged. Contrary to the results ob-
tained in other studies, triglycerides levels were not
affected by the administration of artichoke. Finally,
no statistically significant difference in liver enzymes
was observed between the two groups. Only two
cases of poor tolerability were reported in the 12 in-
dividuals who did not complete the trial. A recent trial
conducted by Bundy and Walzer [56] in 2008 exam-
ined 131 healthy adult individuals affected by slight
to moderate hypercholesterolemia., with total choles-
terol levels in plasma amounting to 6.0-8.0 mmol/l.
The trial was aimed at assessing the effects of arti-
choke leaf extracts on lipid plasma levels and the gen-
eral wellbeing of the individuals. The volunteers were
randomised into two groups: one received 1,280 mg
artichoke extract every day for 12 weeks, and the
other a placebo. In the treated group, total cholesterol
levels in plasma decreased on the average by 4.2%,
while they increased in the control group (by 1.9% on
the average); this means that the difference between
the groups is statistically significant (p = 0.025). On
the other hand, there was no significant difference in
LDL cholesterol, HDL cholesterol and triglycerides
between the groups. Following either treatment, the
enrolled individuals reported an improvement of their
subjective sensation of wellbeing, without any signif-
icant difference between the groups. In conclusion,
consumption of the artichoke leaf extract resulted in a
modest but favourable, statistically significant, differ-
ence in total cholesterol after 12 weeks. Our present
knowledge has now ascertained that, in spite of the
presence of high quantities of lipids in the blood, the
first step towards the development of an atheroma-
tous plaque must take place in the vascular endothe-
lium owing to tissue lesions or oxidative processes.
Most of the recent in-vitro experiments have high-
lighted that the artichoke and its active ingredients not
only induce the reduction of circulating cholesterol
levels, but may also exert a positive effect on the vas-
cular endothelium performance, thus succeeding in
preventing atherosclerosis. Lupattelli and collabora-
tors [57] examined 18 moderately hypocholes-
terolemic individuals (LDL cholesterol ranging be-
tween 130 and 200 mg/dl, triglycerides between 150
and 250 mg/dl) and 10 individuals affected by high
hypercholesterolemia (LDL cholesterol >200 mg/dl,
triglycerides >250 mg/dl), aged between 36 and 60
years. The patients were not treated with a hypocho-
lesterolemizing therapy during the study period and
received 20 ml/die artichoke juice dissolved in water
for 6 weeks. In addition to the usual lipid parameters
in the blood, the levels of various soluble adhesion
molecules, such as VCAM-1, ICAM-1 and E-se-
lectin, were also measured; these molecules are hy-
per-expressed in dyslipidemic individuals. Finally,
the brachial arteria diameter and flow-mediated va-
sodilatation (FMV) of the brachial arteria – two mea-
sures of the arterial dilatation capacity – were veri-
fied. At the end of treatment, an increase in triglyc-
erides levels and a decrease in total and LDL choles-
terol (p <0.05 for all of them) were recorded in the
treated patients; even if the controls showed a signif-
icant decrease in the latter parameters (p <0,01 for
both). There was also a reduction in VCAM-1 and
ICAM-1 (p <0,05 for both), but not in E-selectin.
Brachial FMV increased significantly (p <0,01), and
a subsequent analysis demonstrated that the changes
in adhesion molecule levels and brachial FMV were
well correlated (p <0,05); on the contrary, no correla-
tion was observed between LDL cholesterol and
brachial FMV. In a subsequent discussion on these re-
sults, the Authors pointed out that the potential bene-
ficial effect of the artichoke on the vasodilatation ca-
pability, as observed in their study, seemed to be me-
diated by its antioxidant property, rather than by the
hypocholesterolemizing effect. The latest meta-
analysis on the hypocholesterolemizing action sec-
ondary to the administration of artichoke extract was
conducted by Pittler and collaborators [58]. In this
meta-analysis the authors reviewed 2 clinical trials
conducted with correct methods and involving 167
patients affected by moderate hypercholesterolemia.
The dry artichoke extract, titrated with caffeoylquinic
acid 15%, reduced total cholesterol from 7.74
mmol/l. to 6.31 mmol/l after 42 treatment days
(p<0.01), while the placebo reduced it from 7.69
mmol/l to 7.03 mmol/l. The adverse effects recorded
in either trial were almost negligible.
Finally, an interesting recent research random-
ized, double-blind, placebo-controlled clinical trial
was performed on 92 overweight subjects with pri-
mary mild hypercholesterolaemia for 8 weeks [59].
Verum supplementation with 2-daily oral assump-
tions (before lunch and dinner) of film-coated
tablets of 250 mg of standardized artichoke leaf ex-
tract (>20% caffeoylquinic acids, >5% flavonoids
and >5% cynaropicrin) was associated with a signif-
icant increase in mean high-density lipoprotein
(HDL)-cholesterol (p<0.001) and in mean change in
HDL-cholesterol (HDL-C) (p=0.004). A signifi-
cantly decreased difference was also found for the
mean change in total cholesterol (p=0.033), low-
density lipoprotein (LDL)-cholesterol (p<0.001), to-
tal cholesterol/HDL ratio (p<0.001) and LDL/HDL
ratio (p<0.001), when verum and placebo treatment
were compared.
These data indicates that dry artichoke extracts
can be useful to lower cholesterol levels, but other
adequately rigorous clinical trials still have to be
published to confirm these results. In short, the ac-
tion of the artichoke extract on cholesterolemia is
especially linked to the increase in choleresis and,
21
ARTICHOKE IN PREVENTING CVD: A REVIEW
therefore, to the excretion of biliary salts and acids
rich in cholesterol, but also to a direct action on the
liver, which it is known to play a major role in lipid.
The Artichoke seems to be able to stimulate the
following mechanisms of cholesterol metabolism by
the liver: 1) more effective uptake and subsequent
intra-hepatocyte metabolism of chylomicron rem-
nants; 2) stimulation of apolipoprotein synthesis by
the liver, with the consequent improvement of lipid
metabolism; 3) increased uptake of LDLs and HDLs
by the liver with the improvement of their intra-he-
patocyte metabolism; 4) hepatic HDL synthesis
stimulation induced by increased formation of
apolipoproteins A1 and A2 by the liver. It is well
known that these apolipoproteins, also produced by
the intestine, are essential for the formation of cir-
culating HDLs; 5) increase in HTGL and LCAT syn-
thesis by the liver.
2. Antioxidant action
The artichoke leaf extract induces the concentra-
tion-dependent inhibition of induced oxidative
stress in human neutrophils. Cynarin, caffeic acid,
chlorogenic acid and luteolin have been found to be
the active ingredients that play the major role in the
antioxidant protective activity. The antiradical prop-
erties of aqueous and alcoholic artichoke extracts, as
well as their capability of inhibiting lipid peroxida-
tion, were recently confirmed. As demonstrated by
several studies conducted by Samochowiec [60], ar-
tichoke extracts possess efficacious properties
against the oxidative stress induced by inflamma-
tory process mediators and LDL oxidation. The rad-
ical-scavenger properties of the extract, documented
by in-vitro copper-induced oxidative prevention of
LDLs, are due to the presence of flavonoids and, in
particular, luteolin. Flavonoids act as hydrogen
donors (reducing action) and as chelating substances
capable of binding to catalyzing metals. In practice,
they act as antioxidants because they seize reactive
oxygen species (ROS) and transform them into less
aggressive radicals, thus sacrificing themselves and,
at the same time, saving physiological antioxidants
(carotenoids, glutathione, vit. C and vit. E). The ma-
jor role played by antioxidants in the reduction of
oxidative and degenerative damage to cells and,
consequently, to the tissue is by now widely known.
A recent Italian study conducted in 2008 [61] was
aimed at demonstrating the liver-protecting proper-
ties of polyphenolic artichoke extracts (AE) on rat
hepatocytes and human hepatoma cells. The hepato-
cytes were exposed to H2O2 generated in situ by
glucose-oxdase and then treated with AE, or pure
chlorogenic acid (Cha) or a well-known antioxidant,
N, N’-difenyl-p-phenylenediamine (DPPD). The ad-
dition of glucose-oxidase to the cell culture induced
deplezione intracellular gluthatione depletion
(GSH), malon dialdehyde accumulation (MDA) in
the cultures – an indicator of lipid peroxidation –
and cell death. These results demonstrated that cells
treated with AE were protected against the oxidative
stress caused by glucose-oxidase to a similar extent
to that of DPPD. In addition, AE, wa well as Cha,
prevented total loss of GSH and MDA accumula-
tion. On the contrary, hepatoma cell treatment with
AE for 24 hours determined reduced cell viability in
a dose-dependent manner; however, Cha did not ex-
ert any noteworthy effect on the cell death rate. The
results of this study indicate that AE has a potential
market as an antioxidant that protects hepatocytes
from oxidative stress. In addition, AE reduces via-
bility of human liver cancer cells by supporting their
apoptosis.
3. Hypoglycemizing action
A few compounds found in the artichoke exhib-
ited a significant hypoglycemizing activity in vitro.
Chlorogenic acid was identified by Arion and
collaborators as a powerful and specific glucose-6-
phosphate-translocase inhibitor [62]. This enzyme is
essential for the formation of endogenous glucose
during the gluconeogenesis process, as well as for
the glycolytic process. Chlorogenic acid also seems
to be able to reduce the absorption of the carrier-
favourite intestinal glucose.
All this may contribute to a slight reduction of
glycemia values, which is particularly significant in
non-insulin-dependent diabetic individuals. Matsui
and collaborators [63] isolated some caffeoylquinic
acid derivatives involved in the inhibitory activity of
α-glucosidase and demonstrated that caffeoylquinic
acids exerted a moderate hypoglycemizing effect.
Another compound that is found in artichoke leaves
in considerable quantities and affects glucide metab-
olism is inulin [64]; this compound belongs to the
family of fruit-oligosaccharides (FOS) and exerts
important effects on the intestinal transit, in which it
modulates cholesterol and triglycerides concentra-
tions in the blood and improves intestinal bacterial
flora composition. Various authors have described
the hypoglycemizing activity of the artichoke con-
sumed as food. Vinik [65] in 2002 and, more re-
cently, Nazni [66] in 2006 confirmed that the edible
parts of the plant have good hypoglycemizing prop-
erties, especially due to the presence of high quanti-
ties of alimentary fibre.
Moreover, recently a randomized, double-blind,
placebo-controlled clinical trial was performed in 39
overweight subjects for 2 months. The net change of
the glycaemia was reduced significantly only in the
intervention group; intervention consisted in 3-daily
oral assumptions (before breakfast, lunch and din-
ner) of film-coated tablets of 200 mg of standardized
Cynara scolymus flowering buds extract. Finally, in
the supplemented group, the homeostasis model as-
sessment (HOMA) decreased significantly after in-
tervention; these parameters did not change in the
controls [67].
4. Liver-protecting action
Among the many therapeutic properties that
have been traditionally ascribed to the artichoke, the
liver-protecting action is not certainly the least im-
portant, to the extent that its use was recommended
to patients affected by hepatitis, jaundice, cirrhosis
and liver steatosis. Cynarin and caffeoylquinic acids
are thought to be the substances that are chiefly re-
sponsible for the protective action against such he-
patotoxic agents as carbon tetrachloride. The liver-
protecting action manifests itself in the reduction of
liver malondialdehyde and blood enzymes AST
(Aspartate aminotransferase) and ALT (Alanine
22
M. RONDANELLI ET AL.
aminotransferase), whose increase in serum indi-
cates altered liver performance due to hepatotoxic
damage. The extracts with a higher content in phe-
nol derivatives exert a greater effect on the bile flow
and a better liver-protecting action. Nevertheless,
single administrations of chlorogenic acid in equiv-
alent quantities to those found in the extract do not
produce any choleretic or protective effects. At least
two of the earliest studies on the artichoke had tried
to demonstrate its usefulness in arsenic-poisoned in-
dividuals [68]. Artichoke leaf extracts were tested in
vivo by Maros [69] to verify their regeneration ef-
fects on liver cells. In one experiment, an aqueous
artichoke leaf extract, administered orally in par-
tially hepatectomized rats in 0.5 ml/day doses for 21
days, significantly increased liver tissue regenera-
tion as measured from the residual liver weight, mi-
totic index and liver cell rate. In other experiments
using the same methods the artichoke extract accel-
erated liver weight increase, induced marked hyper-
aemia and increased both binucleated hepatocyte
rate and the liver cell content in ribonucleic acid.
According to the majority of the recent research, lu-
teolin and other polyphenols [48] seem to affect he-
patocyte proliferation induced by different growth
factors, including insulin. The action against exoge-
nous toxic agents was also the subject of various in-
vestigations. Adzet and collaborators [70] reported
that an aqueous artichoke extract (containing 2.2%
caffeoylquinic acids and 0.9% luteolin), adminis-
tered orally in the rat in doses of 500 mg/kg body
weight 48 hours, 24 hours and 1 hour before induc-
ing acute liver intoxication with carbon tetrachlo-
ride, significantly improved the liver performance;
this was evidenced by the decrease in GSH (glu-
tathione) liver content and total bilirubin, direct
bilirubin, GOT and GPT levels in the plasma. Only
cynarin, of the three caffeoylquinic acids, exhibited
notable liver-protecting properties against release of
both GOT and GPT. Various polyphenol compo-
nents [48] of the artichoke leaf have been analysed
and seem to contribute to the liver-protecting and
antioxidant actions; this disagrees with the results
obtained by Adzet [70], who had ascertained that
only cynarin and, to a lesser extent, caffeic acid
were active. These results are of great clinical inter-
est, because this strong protective action is not prob-
ably limited to hepatocytes alone. For example, as
already mentioned, these substances also inhibit
LDL cholesterol oxidation and, consequently, may
prevent atherosclerosis. In 2003 Speroni and collab-
orators [71] tested four different marketed artichoke
leaf extracts, containing different quantities of ac-
tive ingredients, in an animal model. The study re-
sults demonstrated that the extract with the highest
content in phenols exerted the best results in terms
of biliary excretion and liver-protecting activities.
The histological examination of liver samples of
mice poisoned with CCl4 highlighted steatosis,
necrosis, small fibrosis areas and leukocyte migra-
tion; the hepatocytes showed dilatation of the endo-
plasmic reticulum with polyribosome detachment
and disaggregation, as well as cell swelling with
clarity of mitochondrial vacuoles. Similar aspects
also remain unchanged in samples taken from rats
treated with chlorogenic acid and cynarin. On the
contrary, the liver parenchyma of rats treated with
the extract having the highest content in phenols ex-
hibited an almost normal anatomy, without any ma-
jor damage to the endoplasmic reticulum or cell mi-
tochondria.
5. Choleretic action
The artichoke performs a “amphocholeretic”
role, regulating the biliary flow by either decreasing
an exceedingly high biliary secretion or increasing it
whenever it is reduced by toxic factors. The whole
phytocomplex enhances choleresis through the si-
multaneous stimulation of the enzymatic, functional
and antitoxic activities of the liver, liver regenera-
tion and blood flow increase. In fact, it joins the bil-
iary activity to the liver activity, thus justifying its
indication against dyspepsia accompanied by a sen-
sation of a full stomach, abdominal pain, meteorism,
nausea and vomiting.
Experiments conducted in vitro demonstrated
that the dry aqueous extract from artichoke leaves in
primary hepatocyte cultures can induce bile secre-
tion from biliary canaliculi, and that pure or more or
less diluted juices squeezed from fresh leaves exert
a dose-dependent choleretic effect on the isolated,
perfused rat liver; in an experiment conducted by
Matuschowski [72] in 1996, the bile flow increased
by 112 to 150%, with a peak after 20 minutes from
administration. The hepatobiliary and hepatoprotec-
tive effects of artichoke leaf preparations were
demonstrated not only by in-vitro experiments, but
also by a number in-vivo studies. Doses amounting
to 200 mg/kg of an hydro-alcoholic extract from
fresh artichoke leaves (19% of caffeoylquinic acids)
and to 25 mg/kg of an hydro-alcoholic extract from
fresh artichoke leaves – with the latter extract being
purified and enriched in phenolic compounds (46%
of caffeoylquinic acids) – were administered in the
rat by the parenteral route. Both extracts stimulated
choleresis by increasing the content in dry bile
residue and total cholate excretion (flow collection
through incannulation of the bile duct). These same
extracts, administered orally in doses of 400 mg/kg
for the total extract and 200 mg/kg for the enriched
extract, increased intestinal propulsion by 11% and
14% respectively, as was highlighted in the studies
conducted by Saenz Rodriguez and collaborators in
2002 [73] and in those conducted by Speroni in
2003 [71]. Much more recently, in 1993, the
choleretic action of the standardized extract was in-
vestigated by Kirchhoff [74] in a cross-over, double-
blind, randomised, placebo-controlled pilot study. A
single 1.92 g dose was administered in 20 male pa-
tients (mean age 26 years), divided into two groups:
the first group (A) received the active treatment and
then placebo after an 8-day washout period; the sec-
ond group (B) received placebo in the first stage and
the active treatment in the second. The mean in-
crease in secreted bile volume was considerably
higher in treated individuals (I-A and II-B) than in
the placebo groups (I-B and II-A); in particular, the
greatest effect was reached after 1 hour, but the ef-
fects were still evident after 3 hours (always p <0,01
times from the measurements between 30 and 180
minutes in comparison with the baseline values).
During the discussion, the authors pointed out that
23
ARTICHOKE IN PREVENTING CVD: A REVIEW
this data was of an unquestionable clinical impor-
tance; in addition, the artichoke extract consumed
after a meal may be able to affect enzyme digestion
and the intestinal motor function for an actual
length of time of about 120-150 minutes. This
means that the extract can be recommended for
treatment of dyspepsia, especially when the cause
can by ascribed to dyskinesia of biliary ducts or fat
absorption disorders. Neither side effects nor
changes in laboratory parameters were observed
during this study. In 1998, Schulz reported the re-
sults of a small placebo-controlled clinical trial. The
administration of 1,920 mg artichoke extract in 20
volunteers increased bile flow by 127.3% and
151.5% after 30 and 60 minutes respectively. The
effects of the artichoke on gastrointestinal disorders
associated to poor elimination of biliary acids were
investigated in an observation study conducted by
Held [75] in 1991, in which 403 patients affected by
hepatic insufficiency and disorders in the biliary
duct were treated for 4 weeks with standardised ar-
tichoke extract containing 375 mg dry extract per
tablet. The overall results were considered as “very
good” by 37.4% of the patients (34.9% of the physi-
cians) and as “good” by 46.9% of the patients
(52.3% of the physicians). Twelve patients (2.9%)
dropped out of the study - 4 because of diarrhoea
and 2 because of excessive flatulence. The same ex-
tract was used in a similar study conducted by We-
gener in 1994. The extract was administered at the
average dose of 4.75 tablets a day (corresponding to
1,520 mg) in 170 patients affected by different gas-
trointestinal disorders, including dyspepsia (34%),
irritable colon (16%), constipation (22%), func-
tional biliary duct disorders (21%), and others. Af-
ter 6 weeks’ treatment, there was an unexpected
marked reduction of vomiting (95%), nausea (85%)
and abdominal pain (75.5%). Abdominal pain, inap-
petence and meteorism also improved. According to
the patients, the results were generally considered as
excellent (22%) or good (67%). Unwanted side ef-
fects (weakness and a sensation of hunger) were ob-
served only in 1.2% of the patients. Another large
multicentre phase IV clinical trial, with treatment
lasting 43.5 days on the average, was conducted by
Fintelmann and Menßen [76] in 1996 in 553 pa-
tients (mean age 54.7 years) suffering from dyspep-
sia. The administration of 3 to 6 tablets of standard-
ised extract containing 375 mg dry extract per tablet
resulted in the significant reduction of dyspeptic
symptoms within 6 treatment weeks and the im-
provement of general symptoms in 70% of the
cases. In comparison with baseline values, the sub-
jective reduction of symptoms was about 66% for
meteorism, 76% for abdominal pain, 82% for nau-
sea and 88% for vomiting. According to the physi-
cian’s opinion, the general average therapeutic effi-
cacy, on the basis of a classification scale ranging
from 1 (excellent) to 5 (poor), amounted to 1.95.
The effects were considered as “good” or “excel-
lent” in about 87% of the patients and occurred
within 10 days from treatment. Only slight side ef-
fects were recorded (weakness and flatulence).
Other more recent studies were also conducted to
ascertain the capability of the artichoke extract of
improving dyspepsia symptoms.
Riassunto
Il carciofo, Cynara scolymus, è una delle più an-
tiche piante coltivate nel mondo, ed suoi estratti, ot-
tenuti da diverse parti della pianta (foglie, frutti e
radici), sono stati utilizzati come medicamenti da
tempo immemorabile. Gli effetti farmacologici e te-
rapeutici del carciofo sul fegato erano già noti nel
17 ° secolo. Gli studi moderni, iniziati nel secolo
scorso, hanno confermato le proprietà stimolanti
degli estratti di carciofo sul fegato e sulla cistifellea.
La ricerca in questo campo è stata inizialmente con-
centrata sugli effetti diuretico e coleretico, esercitati
dagli estratti di carciofo sia sugli animali sia nel-
l’uomo. Poi sono state dimostrate altre importanti
proprietà terapeutiche, come l’attività ipolipemiz-
zante, l’attività antiossidante e ipoglicemizzante.
Questa review enumera gli studi più significativi che
hanno evidenziato queste proprietà terapeutiche.
Informazioni in merito alla possibilità terapeutiche
offerte dalla medicina complementare evidence-ba-
sed devono essere diffuse e tali possibilità terapeu-
tiche integrate nella pratica clinica, anche per le
persone con disturbi metabolici al fine di prevenire
le malattie cardiovascolari.
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... Caffeoylquinic acid is another component found in the and can inhibit α-glucosidase and exert a synergistic effect to control the glycemic index. 57 Inulin is a fructooligosaccharide (FOS) can potentially improve the intestinal motility and transit, which may act as an essential regulator of glucose homeostasis and glycemic indices levels. [57][58][59] It can also change the secretion of glucagon-like peptide-1, promote β-cell proliferation and reduce β-cell apoptosis. ...
... 57 Inulin is a fructooligosaccharide (FOS) can potentially improve the intestinal motility and transit, which may act as an essential regulator of glucose homeostasis and glycemic indices levels. [57][58][59] It can also change the secretion of glucagon-like peptide-1, promote β-cell proliferation and reduce β-cell apoptosis. 14 Inulin, in its way, can improve the modulation of the gut microbiome via the formation of short-chain fatty acids (SCFA) and secondary bile acids. ...
... SCFA could also participate in maintaining the insulin signaling pathway and energy homeostasis. [57][58][59] Reduction of lipopolysaccharide (LPS), as a component of the outer membrane of Gram-negative bacterium, by inulin is involved in the normal microbial balance. LPS can be involved in the development of inflammation, and insulin resistance. ...
Article
Objectives Cynara scolymus L. (common artichoke) and its products have been considered as potential phytotherapeutic agents for various conditions, such as cardiovascular, hepatic and gastric diseases, among others. Until now, the effects of artichoke and artichoke products administration on glycemic indices have not been sufficiently appraised. The present study evaluated the effects of artichoke and artichoke products administration on the glycemic indices. Methods Clinical trials were identified in the Cochrane Library, PubMed, Embase and Scopus databases; to infinity until 15 March 2020. Weighted mean differences (WMD) were pooled using a random-effects model. Heterogeneity, sensitivity analysis and publication bias were reported using standard methods. Results Pooled analysis of nine Randomized controlled trials (RCTs), demonstrated that the administration of artichoke and artichoke products led to a significant reduced fasting blood sugar (FBS) (WMD: -5.28 mg/dl, 95% CI: -8.95, -1.61; p = 0.005). However, other glycemic indeces including fasting insulin (WMD: -0.45 μIU/dL, 95% CI: -1.14, 0.25; p = 0.20), HOMA-IR (MD: -0.25, 95% CI: -0.57, 0.07; p = 0.12) or Hemoglobin A1c (HbA1c) (WMD: -0.09, 95% CI: -0.20, 0.02; p = 0.09) did not alter after the administration of artichoke and artichoke products. A subgroup analysis comparing the kind of intervention, revealed that just the supplementation of artichoke and artichoke products, in a noco-supplementation form, was efficacy for the reduction of Homeostatic model assessment of insulin resistance (HOMA-IR) (WMD: -0.52, 95% CI: -0.85, -0.19; p = 0.002) Conclusions The supplementation of artichoke and artichoke products can significantly reduce the FBS concentrations in humans. Moreover, these outcomes suggested that just the supplementation of artichoke and artichoke products is more effective in the reduction of HOMA-IR levels than the co-supplementation form. However, additional clinical trials with longer study periods are necessitated to obtain a robust conclusion for producing new guidelines as part of a healthy diet.
... Cynara Cardunculus represents a solid component of a traditional Mediterranean diet [31], which displays potential lipid lowering and hepato-protective properties [32]. In particular, phytochemical studies revealed that Cynara Cardunculus Extract (CyC) is rich in antioxidants such as caffeic acid derivatives, (e.g., mono-caffeoylquinic acid and dicaffeoylquinic acid such as cynarin and chlorogenic acid), flavonoids (including the glycosides luteolin-7-beta-rutinoside, luteolin-7-beta-glucoside, and luteolin-4-beta-D-glucoside), and sesquiterpenes such as 5%-10% cynaropicrin [32,33]. ...
... In addition, daily supplementation with CyC antagonized liver steatosis in rats fed a HFD, suggesting that active ingredients found in the herbal extract from wild types of artichoke produce simultaneous antagonistic effects on both dietinduced metabolic imbalance and liver injury. This is in accordance with previous data suggesting that artichoke derivatives possess metabolic regulatory properties and that an overall improvement of NAFLD condition may be detected when such a nutraceutical supplementation occurs both in experimental models of liver dysfunction and in patients [31,32]. ...
... In particular, evidence exists that Cynara extracts produce an improvement of lipid metabolism in liver cells [31,32,40]. Several mechanisms have been implicated in hypolipemic effects of nutraceutical supplementation with Cynara derivatives based on biomolecular studies carried out both in vitro and in vivo [31,32,41,42]. ...
Article
Full-text available
Hyperlipidemia and insulin-resistance are often associated with Non-Alcoholic Fatty Liver Disease (NAFLD) thereby representing a true issue worldwide due to increased risk of developing cardiovascular and systemic disorders. Although clear evidence suggests that circulating fatty acids contribute to pathophysiological mechanisms underlying NAFLD and hyperlipidemia, further studies are required to better identify potential beneficial approaches for counteracting such a disease. Recently, several artichoke extracts have been used for both reducing hyperlipidemia, insulin-resistance and NAFLD, though the mechanism is unclear. Here we used a wild type of Cynara Cardunculus extract (CyC), rich in sesquiterpens and antioxidant active ingredients, in rats fed a High Fat Diet (HFD) compared to a Normal Fat Diet (NFD). In particular, in rats fed HFD for four consecutive weeks, we found a significant increase of serum cholesterol, triglyceride and serum glucose. This effect was accompanied by increased body weight and by histopathological features of liver steatosis. The alterations of metabolic parameters found in HFDs were antagonised dose-dependently by daily oral supplementation of rats with CyC 10 and 20 mg/kg over four weeks, an effect associated to significant improvement of liver steatosis. The effect of CyC (20 mg/kg) was also associated to enhanced expression of both OCTN1 and OCTN2 carnitine-linked transporters. Thus, present data suggest a contribution of carnitine system in the protective effect of CyC in diet-induced hyperlipidemia, insulin-resistance and NAFLD.
... Cynara Cardunculus represents a solid component of a traditional Mediterranean diet [31], which displays potential lipid lowering and hepato-protective properties [32]. In particular, phytochemical studies revealed that Cynara Cardunculus Extract (CyC) is rich in antioxidants such as caffeic acid derivatives, (e.g., mono-caffeoylquinic acid and dicaffeoylquinic acid such as cynarin and chlorogenic acid), flavonoids (including the glycosides luteolin-7-beta-rutinoside, luteolin-7-beta-glucoside, and luteolin-4-beta-D-glucoside), and sesquiterpenes such as 5%-10% cynaropicrin [32,33]. ...
... In addition, daily supplementation with CyC antagonized liver steatosis in rats fed a HFD, suggesting that active ingredients found in the herbal extract from wild types of artichoke produce simultaneous antagonistic effects on both dietinduced metabolic imbalance and liver injury. This is in accordance with previous data suggesting that artichoke derivatives possess metabolic regulatory properties and that an overall improvement of NAFLD condition may be detected when such a nutraceutical supplementation occurs both in experimental models of liver dysfunction and in patients [31,32]. ...
... In particular, evidence exists that Cynara extracts produce an improvement of lipid metabolism in liver cells [31,32,40]. Several mechanisms have been implicated in hypolipemic effects of nutraceutical supplementation with Cynara derivatives based on biomolecular studies carried out both in vitro and in vivo [31,32,41,42]. ...
Preprint
Full-text available
Hyperlipidemia and insulin-resistance are often associated with Non Alcoholic Fatty Liver Disease (NAFLD) thereby representing a true issue worldwide, due to increased risk of developing cardiovascular and systemic disorders. Although clear evidence suggests that circulating fatty acids contribute in pathophysiological mechanisms underlying NAFLD and hyperlipidemia, further studies are required for better identify potential beneficial approaches for counteracting such a disease state. Recently, several artichoke extracts have been used for both reducing hyperlipidemia, insulin-resistance and NAFLD, though the mechanism is unclear. Here we used a wild type of Cynara Cardunculus extract (CyC), rich in sesquiterpens and antioxidant active ingredients, in rats fed and High Fat Diet (HFD) compared to Normal Fat Diet (NFD). In particular, in rats fed HFD for four consecutive weeks, we found a significant increase of serum cholesterol, triglyceride and serum glucose. This effect was accompanied by increased body weight and by histopathological features of liver steatosis. The alterations of metabolic parameters found in HFD were antagonised dose-dependently by daily oral supplementation of rats with CyC 10 and 20 mg/Kg over 4 weeks, an effect associated to significant improvement of liver steatosis. The effect of CyC (20 mg/Kg) was also associated to enhanced expression of both OCTN1 and OCTN2 carnitine-linked transporters. Thus, present data suggest a contribution of carnitine system in the protective effect of CyC in diet-induced hyperlipidemia, insulin-resistance and NAFLD.
... In fact, we found in subjects from the Altilix ® supplemented vs. placebo groups, regarding MetS comorbidities, a significant improvement in glucose metabolism parameters (including HbA1c, insulin resistance, and pancreatic β-cell function), in agreement with some in vitro and in vivo literature data [34][35][36]. In particular, among these, some in vivo studies with oral daily administration of Cynara cardunculus (L.) subsp. ...
... scolymus Hayek extract showed glycemic-lowering effects. Other studies reported in 39 overweight subjects, that the intake of tablets containing extract of artichoke during meals, resulted in a significant reduction of the HOMA index [34]. Whereas, in vitro studies evidenced the role of chlorogenic acid on glucose regulation-antagonist in glucose transport, inhibitor of α-amylase and α-glucosidase, and therefore in the post-prandial glucose blood concentration [34][35][36]. ...
... Other studies reported in 39 overweight subjects, that the intake of tablets containing extract of artichoke during meals, resulted in a significant reduction of the HOMA index [34]. Whereas, in vitro studies evidenced the role of chlorogenic acid on glucose regulation-antagonist in glucose transport, inhibitor of α-amylase and α-glucosidase, and therefore in the post-prandial glucose blood concentration [34][35][36]. We also found, after Altilix ® supplementation, an improvement in both HOMA-IR (marker of insulin resistance), a marker useful in identifying individuals with metabolic NAFLD [37] and HOMA-β (marker of pancreatic β-cell function). ...
Article
Full-text available
The objective was to evaluate the effects of 6 months of supplementation with Altilix ® , containing chlorogenic acid and its derivatives, and luteolin and its derivatives, on cardiovascular risk and hepatic markers in subjects with metabolic syndrome (MetS). A randomized, double-blind, placebo-controlled study was performed in 100 subjects with MetS with a follow-up period of 6 months; 50 subjects were randomized to Altilix ® (26 men and 24 women, mean age 63 ± 8 years) and the other 50 to placebo (28 men and 22 women, mean age 63 ± 11 years). Anthropometric, cardiometabolic, and hepatic parameters were assessed at baseline and at the end of follow-up. Carotid intima-media thickness and endothelial function were assessed by doppler ultrasound and by flow-mediated dilation of the brachial artery, respectively. The presence and degree of non-alcoholic fatty liver disease (NAFLD) was assessed by the fatty liver index (FLI), and subjects were divided into three subgroups: (1) without NAFLD; (2) with borderline NAFLD; and (3) with NAFLD. After 6 months of Altilix ® supplementation, we found a significant improvement vs. placebo in most of the evaluated parameters, including body weight (−2.40% (95% CI −3.79, −1.01); p < 0.001), waist circumference (−2.76% (95% CI −4.55, −0.96); p = 0.003), HbA1c (−0.95% (95% CI −1.22, −0.67); p < 0.001), plasma lipids, FLI (−21.83% (95% CI −27.39, −16.27); p < 0.001), hepatic transaminases, flow-mediated dilation (10.56% (95% CI 5.00, 16.12); p < 0.001), and carotid intima-media thickness (−39.48% (95% CI −47.98, −30.97); p < 0.001). Further, the improvement in cardiometabolic variables was independent of the degree of hepatic steatosis. Altilix ® supplementation improved hepatic and Nutrients 2019, 11, 2580 2 of 17 cardio-metabolic parameters in MetS subjects. Altilix ® supplementation was a beneficial approach in the management of hepatic and cardiometabolic alterations in MetS subjects.
... Artichokes have several healthy properties including antioxidant activity, lipid and cholesterol reduction, and a decrease in postprandial glycemic and insulin response [58][59][60]. Components of artichokes which have an effect are caffeic acid derivatives, flavonoids, such as luteolin, cynaroside, scolymoside, and cynarotrioside and sesquiterpenic lactones; artichokes decrease production of cholesterol and endogenous triglycerides and increase their excretion by bile production [21,61,62]. In several clinical trials, reductions in cholesterol levels were found but more studies are needed [63][64][65][66]. ...
Article
Full-text available
Mortality due to cardiovascular disease (CVD), including cerebrovascular disease (CED) and ischaemic heart disease (IHD), was considerably different in eight municipalities of the province of Castellón, Community of Valencia (Spain) during the period of 1991-2011. In addition, these villages showed differences in agricultural practices and production. Since high vegetable consumption has been linked to decreased all-cause, CVD, and CED mortalities, we hypothesized that the diversity in vegetable and artichoke production, used as proxies for their consumption, could be associated with the diversity of mortality rates. In order to test our hypothesis, we estimated the smoothed standardized mortality ratios (SMRs) of CVD, CED, and IHD mortalities and a directed, age-adjusted mortality rate (AMR). We used a multilevel linear regression analysis to account for the ecological nature of our study. After adjustment, the CVD and CED SMRs were inversely associated with vegetable and artichoke production, with a reduction in SMRs for CVD: -0.19 (95% Confidence Interval [CI] -0.31 to -0.07) and -0.42 (95% CI -0.70 to -0.15) per hectare/103 inhabitants, respectively. The SMRs for CED also decreased: -0.68 (95% CI -1.61 to -0.19) and -1.47 (95% CI -2.57 to -0.36) per hectare/103 inhabitants, respectively. The SMRs for IHD were not associated with vegetal and artichoke production. When the directed AMR was used, CED mortality was consistent with the previous results, whereas the CVD mortality association was lost. Our results indicate that vegetable and artichoke production may act as protective factors of CED and CVD mortalities.
... In fact, artichoke was proven to act upon lipid metabolism by inducing a reduction in cholesterol production, by reducing its biosynthesis through the inhibition of β-hydroxy β-methylglutaryl-CoA (HMG-CoA) reductase [76] and by favoring its excretion. Moreover, artichoke increases bile production, which in turn increases cholesterol elimination [77,78]. Regarding the hypolipidemic action of Capsicum annuum L., both in vitro and in vivo studies have demonstrated how it can reduce TC, triglycerides, and LDL-C, while causing a possible increase in HDL-C [79]. ...
Article
Full-text available
Nephropathic patients show elevated cardiovascular morbidity and mortality compared to the general population. In order to delve deeper into the understanding of this phenomenon, it is necessary to recognize risk factors that are distinctive to the uremic state, such as oxidative stress and chronic low-grade inflammation. Moreover, gender differences have been reported in nephrology, as it has been observed that chronic kidney disease has higher prevalence in males than in females. The use of an oral food supplement (OFS) containing natural active compounds from Capsicum annuum L., Garcinia cambogia, Centella asiatica L., artichoke, and Aesculus hippocastanum L. which are virtually devoid from side effects, but rich in antioxidant and antiradical properties, could represent a valid therapeutic adjunct in the clinical management of nephropathic patients. Moreover, quantitative analysis performed in vitro on such compounds showed that they expressed good total antioxidant (7.28 gallic acid equivalents) and antiradical activity (above 80%). In this study, 23 male nephropathic patients and 10 age and body composition parameter matched healthy males (control group) were enrolled and took 3 cps/day of OFS for 5 weeks. At the end of the study, the nephropathic patient group showed a statistically significant reduction in the following laboratory parameters: total cholesterol (TC) (), atherogenic index TC/high-density lipoprotein cholesterol (), inflammatory parameters (C-reactive protein, , and erythrocyte sedimentation rate, ), systolic (), and diastolic arterial blood pressure (). Regarding body composition, there was an increase in total body water % () with redistribution of extracellular water % () and intracellular water % (). In the control group, there was a reduction in fat mass % () and extracellular water % (). Therefore, this OFS may represent a valid adjunct therapy to counteract comorbidities related to uremia. 1. Introduction During the last century, a substantial increase in the incidence of chronic noncommunicable diseases (NCDs), such as cardiovascular diseases (CVD), chronic kidney disease (CKD), diabetes mellitus (DM), and cancer, has been observed [1, 2]. Up to this day, NCDs represent the primary cause of death in both developed and developing countries [3]. In this context, prevention, especially through following a healthy diet and leading an active lifestyle, becomes of paramount importance [4, 5]. Amongst NCDs, CKD represents a health problem with significant worldwide impact, its global prevalence being estimated between 7 and 12% [6]. Its increase in prevalence, especially during recent years, is related to different factors. Firstly, it is linked not only to the global ageing of the population [7] but also to the concomitant increase in prevalence of other risk factors such as arterial hypertension (AH), DM, and metabolic syndrome, and thanks to more attentive diagnosis performed by clinicians [8]. Patients affected by CKD frequently present a series of comorbidities, prevalently at the cardiovascular (CV) level; therefore, a new clinical entity has been defined as “type IV cardiorenal syndrome,” characterized by the presence of chronic renal failure which induces a reduction in cardiac function, left ventricular hypertrophy, and increased risk to develop CV complications [9]. Amongst factors related to cardiac dysfunction in CKD patients [10], volume overload and blood pressure increase must be considered as they contribute in producing left ventricular hypertrophy [11]. In fact, CKD patients show an elevated prevalence of AH, principally correlated with extracellular volume expansion [12]; in turn, this induces a decline in cardiac function [13]. A study has highlighted how, in these patients, systolic blood pressure values positively correlate with the expansion of extracellular fluid whilst the latter is inversely correlated with the glomerular filtration rate (GFR) [14]. Other CV risk factors typical of the uremic state are chronic low-grade inflammation, hyperhomocysteinemia [15, 16], insulin resistance, and malnutrition-inflammation-atherosclerosis syndrome [17, 18], which contribute to accelerate the atherosclerotic process. Moreover, the gradual accumulation of uremic toxins in the organism, which increases as GFR decreases, plays a key role in CV alterations [19–21] . Uremic toxins can precipitate in the progression of CKD, through various mechanisms such as renal fibrosis, loss of antioxidant defenses, dysfunction, and apoptosis of renal tubular cells and endothelial cells, contributing to the generation and propagation of the chronic low-grade inflammatory state which characterizes this pathology [22–24]. Regarding the increment in oxidative stress (OS), which can be observed in CKD patients [25], it is important to consider that the kidney represents one of the most metabolically active organs, which renders it particularly vulnerable to oxidative damage [26–29]. Interestingly, gender differences have been documented in the field of nephrology and in this regard women seem to be protected from developing end-stage renal disease (ESRD) [30, 31]. A screening study has highlighted how the cumulative incidence of ESRD is lower in women during reproductive age and starts increasing 10 years later than in men [31]. This has been confirmed in a Japanese population study, which pointed out that the incidence and the prevalence of ESRD was higher in men compared to women and that the average age at the beginning of renal replacement therapy was higher [30, 31]. In recent years, numerous in vitro and in vivo studies have focused on researching natural bioactive compounds, which would be ideally free from side effects and would increase the therapeutic potential of standard treatments, as well as having a preventive role in the development of CKD comorbidities [32]. Up to this day, more than 5000 phytocompounds are known, and it is estimated that a large number of these are yet to be discovered [33]. Amongst these, there are vitamins, minerals, flavonoids, phenolic acids, alkaloids, and carotenoids [34–36]. Different classes of phytocompounds act on the organism through various mechanisms and, depending on their polyphenol and antiradical content, perform different antioxidant, cardioprotective, antiproliferative, anti-inflammatory, and hepatoprotective roles. In particular, the oral food supplement (OFS) used in the present study contains a number of plant dry extracts, listed as follows: Capsicum annuum L., which stimulates metabolism; Garcinia cambogia, as a potential antiobesogenic agent [37, 38]; Centella asiatica L., which improves microcirculatory parameters [39, 40]; Cynara scolymus L. or artichoke, which has an antioxidant and depurative function; and Aesculus hippocastanum L. bark extract, which improves the regularity of bowel movements and digestive system functionality. The present study sets out to evaluate the potential therapeutic effect of this OFS on CV risk and body composition, in male CKD patients versus healthy controls. 2. Material and Methods The study was structured into two phases: (1)In vitro phase: qualitative and quantitative HPLC-DAD characterization of the active compounds present in the selected OFS, followed by the evaluation of its antioxidant and free-radical scavenger properties.(2)In vivo phase: administration of the characterized OFS to CKD patients and healthy subjects (control group). 2.1. Oral Food Supplement, Polyphenol Total Content, and Antioxidant Capacity In Vitro The OFS used in the present study contains a number of plant dry extracts: Capsicum annuum L. present in 60 mg, Garcinia cambogia present in 60 mg, Centella asiatica L. present in 100 mg, Cynara scolymus L. or artichoke present in 60 mg, and Aesculus hippocastanum L. bark extract present in 80 mg. The OFS is formulated in capsules, produced under carefully controlled conditions. Controls are performed continuously throughout the process and guarantee that the capsules conform to the highest quality standards. The excipients used are titanium dioxide (2.0000%) and gelatin (qsp 100%). This OFS has been registered with the Italian Ministry of Health with the number 79086. The extraction of 400 mg of OFS powder was made in 4.0 ml H2O adjusted to pH 2.4 by the addition of HCOOH. The extract was stirred at room temperature for 30 min, centrifuged at 14.000 rpm for 5 min, and analyzed. 2.1.1. HPLC-DAD Analysis Analyses of flavonols, hydroxycinnamic acids, and coumarins were carried out using an HP 1100 L liquid chromatograph equipped with a DAD detector and managed by an HP 9000 workstation (Agilent Technologies, Palo Alto, CA, USA). Compounds were separated by using a i.d. 5 μm LUNA C18 column (Phenomenex, USA). UV/Vis spectra were recorded in the 190-600 nm range, and the chromatograms were acquired at 250, 280, 330, and 350 nm. The samples were analyzed by gradient elution at a flow rate of 0.8 ml/min. The mobile phase was a multistep linear solvent gradient system, starting from 95% H2O (adjusted to pH 2 by HCOOH) up to 100% CH3CN in 53 minutes. The chemical reagents used were HPLC grade, acetonitrile (CH3CN) HPLC grade, ethanol (EtOH) HPLC grade, Folin-Ciocalteu reagent, and sodium carbonate (Na2CO3); all were purchased from Sigma-Aldrich (St. Louis, Mo, USA). 2.1.2. Identification and Quantification of Individual Compounds The identity of polyphenols was acquired using data from HPLC-DAD analysis, by comparison with bibliographic data, combination of retention times, and UV/Vis spectra with those of authentic standards. The quantification of individual polyphenolic compounds was performed directly by HPLC-DAD using a five-point regression curve () in the range of 0-30 μg. In particular, flavonols like the quercetin derivatives were determined at 350 nm using rutin as a reference compound, and hydroxycinnamic acid derivatives were determined at 330 nm using ferulic acid as a reference compound, while coumarins were determined at 330 nm using aesculin as a reference compound. In all cases, actual concentrations of the derivatives were calculated after applying corrections for differences in molecular weight. Each sample was analyzed in triplicate, in order to express the analytical results as an average. 2.1.3. Total Phenolic Content and Total Antioxidant Capacity The total phenolic content was determined using the Folin-Ciocalteu method, described by Singleton et al. [41] and slightly modified according to Dewanto et al. [42]. To 125 μl of the suitably diluted sample extract, 0.5 ml of deionized water and 125 μl of the Folin-Ciocalteu reagent were added. The mixture was kept in the darkness for 6 minutes, and then 1.25 ml of a 7% aqueous Na2CO3 solution was added. The final volume was adjusted to 3 ml with water. After 90 minutes, the absorption was measured at 760 nm against water as a blank. The total amount of phenols was expressed as gallic acid equivalents (GAE, mg gallic acid/100 g sample) through the calibration curve of gallic acid. The calibration curve ranged from 20 to 500 μg/ml (). The phenol content was correlated with the in vitro antioxidant activity, as previously confirmed by comparisons with different electron transfer reaction assays and in vitro human low-density lipoprotein (LDL) assays [43–45]. 2.1.4. Antiradical Activity Free radical scavenging activity was evaluated with the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH⋅) assay. The antiradical capacity of the sample extracts was estimated according to a slightly modified procedure reported by Brand-Williams et al. [46]. Two ml of the sample solution, suitably diluted with ethanol, was added to 2 ml of an ethanol solution of DPPH⋅ (0.0025 g/100 ml), and the mixture was kept at room temperature. After 20 minutes, the absorption was measured at 517 nm with a Lambda 25 spectrophotometer (PerkinElmer) versus ethanol as a blank. Successively, the absorption of the DPPH⋅ solution was checked. The antiradical activity is calculated by plotting the ratio , where is the absorption of the DPPH⋅ solution and is the absorption of the DPPH⋅ solution after addition of the sample, against the concentration of the sample. 2.2. CKD Patients and Control Group Men affected by CKD and healthy subjects (control group), aged 18-80 years, were considered suitable for the study. The study protocol complied with the declaration of Helsinki and was appointed by the Ethical Committee of Fondazione Policlinico Tor Vergata (PTV) of Rome. The flow chart of the study is summarized in Figure 1.
... As a folk medicine, globe artichoke has been described more extensively than the other two varieties. It is used since ancient times by Egyptians, Greeks, and Romans (de Falco et al., 2015;Lattanzio et al., 2009) for its leaf (Ben Salem et al., 2015), root (Rondanelli, Monteferrario, Perna, Faliva, & Opizzi, 2013) and usually for immature inflorescence or flower head for improvement of liver functions and lipid-lowering effects among others (Rouphael et al., 2016;Speroni et al., 2003) and dyspepsia (Holtmann et al., 2003). Also, non-classical medical applications have also emerged more recently to include its usage as anti-aging in cosmetics (D'Antuono et al., 2018), treatment of metabolic disorders (Kwon, Kim, & Choi, 2018), anti-oxidant in malignant cells (Jiménez-Moreno et al., 2019), anti-cholinesterase (Turkiewicz, Wojdylo, Tkacz, Nowicka, & Hernandez, 2019), immunosuppressive (Hueza, Gotardo, da Silva Mattos, & Gorniak, 2019) and HCV (Elsebai, Abass, Hakkola, Atawia, & Farag, 2016). ...
Article
Full-text available
Cynara cardunculus L. with its three botanical varieties are presented as potential food and drug resources. Its young flower heads are commonly consumed as a principal part of different Mediterranean dishes, especially the globe artichoke, whereas its different plant parts are considered potential sources of valuable phytoconstituents, mainly polysaccharides, and polyphenols. These chemicals contribute to its nutrition, industry, and bioactivities, including hepatic-and cardiovascular protection and inflammation disorders. A holistic comparative study of artichoke phytochemicals make-up as determinants of its quality, nutritive value and health benefits is presented for its different varieties. Such reviewed evidence is an essential prerequisite for a future better selection of certain variety, and or utilization in therapeutic, food and pharmaceutical applications. The review presented few endeavors for the development of potential novel functional foods fortified with artichoke extracts and/or its bioactive which are of value and need to be more recognized commercially.
... Extracts exert a diastolic effect on the gallbladder and bile ducts, causing an increase in the production of bile acid by liver cells [6]. Many authors emphasize that long-term dietary supplementation with artichoke extract significantly improves blood lipid profile [2,[7][8][9]. Antioxidants contained in the extract can also protect the liver from the harmful effects of toxins, heavy metals, and other chemicals [5,10]. ...
... In fact, evidence has been collected that micronization and co-grinding of both drugs and nutraceuticals leads to a better absorption and tissue distribution of orally given compounds. 43,44 On the other hand, the combination of BPF and CyC seems to represent more than a simple blend of two plant extracts, due to the synergistic response compared to single doses of both products, being the mechanism of synergism to be better elucidated. ...
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Background and aim Non-Alcoholic Fatty Liver Disease (NAFLD) represents a risk factor for cardiovascular diseases. NAFLD is worsened by the simultaneous occurrence of type 2 diabetes mellitus (T2DM) causing an enhancement of inflammatory and fibrotic processes. Although insulin resistance appears the link between NAFLD and T2DM, current pharmacological treatments of T2DM failed to produce relevant benefits in preventing T2DM-related liver dysfunction. In this randomized, double blind, placebo-controlled clinical study, we evaluated the effect of Bergacyn, an innovative formulation originating from the combination of Bergamot Polyphenolic Fraction (BPF) and Cynara cardunculus (CyC). Experimental procedure 80 adult patients with a history of at least 12 months of T2DM and NAFLD received orally BPF (300 mg/daily) Cyc (300 mg/daily), separately or formulated in combination 50/50% (Bergacyn; 300 mg/daily), or placebo all containing 300 mg of bergamot albedo fibers micronized and co-grinded as excipients. Results and conclusion Serum measurements and liver ultrasound analyses showed that concomitant administration of BPF and CyC produced significant improvement of NAFLD biomarkers in patients with T2DM. This effect was associated with a substantial reduction of oxidative stress/inflammatory biomarkers, thus contributing to a significant improvement of NO-mediated reactive vasodilation. Furthermore, the effect of Bergacyn showed a synergistic effect of both extracts, thus suggesting that this peculiar formulation represents a novel therapeutic strategy to counteract vascular inflammation and endothelial dysfunction in patients suffering from T2DM and NAFLD. Further studies in larger cohort of diabetic patients are required to better identify the potential of Bergacyn on metabolic disorders accompanying T2DM and NAFLD.
Article
Large quantities of non-edible parts of the artichoke plant (Cynara cardunculus L.) comprising leaves, stems, roots, bracts, and seeds are discarded annually during industrial processing. These biowastes also contain high moisture making them susceptible to microbial growth and consequently may cause environmental contamination. However, these by-products are high in many phytochemicals similar to those of its edible flower heads including dietary fibers, phenolic acids, sesquiterpene lactones, enzymes, and flavonoids. Based on worldwide interest in renewable resources of energy, pharmaceutically-active biomolecules, and foods, many recent investigations have been conducted on recycling and the optimization the downstream processes for maximal exploitation of agri-food biowastes. Valorization of C. cardunculus L. biowastes presents opportunities for applications in the food (such as natural preservatives and milk coagulant) and non-food (such as therapeutics, biofuels, and paper pulp production) industries. This review focuses on the state-of-the-art for valorization practices of C. cardunculus L. biowastes and suggests potential novel uses in food and non-food industries. Different optimization techniques combining downstream and white biotechnology processes to develop better utilization of artichoke biowastes are presented.
Conference Paper
Although largely unproven in humans, better resistance to pathogens, reduction in blood lipids, antitumor properties, hormonal regulation and immune stimulation may all be possible through gut microflora manipulation. One approach advocates the oral intake of live microorganisms (probiotics). Although the probiotic approach has been extensively used and advocated, survivability/viability after ingestion is difficult to guarantee and almost impossible to prove. The prebiotic concept dictates that non viable dietary components fortify certain components of the intestinal flora (e.g., bifidobacteria, lactobacilli). This concept has the advantage that survival of the ingested ingredient-through the upper gastrointestinal tract is not a prerequisite because it is indigenous bacterial genera that are targeted. The feeding of oligofructose and inulin to human volunteers alters the gut flora composition in favor of bifidobacteria, a purportedly beneficial genus. Future human studies that exploit the use of modern molecular-based detection methods for bacteria will determine the efficacy of prebiotics. It may be possible to address prophylactically certain gastrointestinal complaints through the selective targeting of gut bacteria.