Folium Cynarae

Definition
Folium Cynarae consists of the dried basal leaves of Cynara cardunculus
L. (Asteraceae) (1–4).
Note: The fresh lower part of the flower head is official in the African
pharmacopoeia (5).

Synonyms
Cynara scolymus L. was the name of the plant cited in the above-men-
tioned pharmacopoeias and monographs. However, the correct name of
the plant is Cynara cardunculus L. (Asteraceae) according to the current-
ly accepted nomenclature (6).

Selected vernacular names

Alcachofa, alcachofra, alcaucil, alcaucoe, artichaut, artichaut commun,
artichiocco, artichoke, artichoke thistle, Artischocke, artiskok, carcioffa,
carciofo, carciuffolo, cardo alcachofero, cardo de comer, cardo sen-
zaspine, cardoon, dofital ‘roza, edible thistle, enginar, garden artichoke,
Gemüseartischocke, globe artichoke, hathi choka, hatichuk, kangar, kan-
gar I dahri, kharshoul, kharsuf, kunjor, Scotch thistle, som-eonggeongqui
(2, 3, 5, 7–13).

Geographical distribution
Native to the Mediterranean, northern Africa and southern Europe, and
the Canary Islands; cultivated in subtropical regions (8, 14, 15).

Description
A large herbaceous perennial, thorny plant, approximately 1.5 m in
height. The leaves are large, alternate, deeply dentate. The tall purple
flowers are grouped in large capitulums, 10–15 cm in diameter borne
by hardy ramified grooved stems, with sessile and almost entire leaves
(5, 14, 16).

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Plant material of interest: dried leaves

General appearance
Leaves are very large, up to approximately 50 cm long by 25 cm wide with
a long petiole approximately 1 cm thick; lamina deeply pinnatifid, forming
flat, lanceolate segments with coarsely-toothed margins; upper surface
brownish-green, lower surface greyish-white and densely covered with
trichomes; segments with pinnate venation, the side veins terminating in a
short point on each marginal tooth; midrib and petiole deeply grooved on
the upper surface, the lower surface prominently raised, with several lon-
gitudinal ridges and covered with long, whitish trichomes (1, 2, 17).

Organoleptic properties
Odour: faint, slightly sour; taste: salty at first, then bitter (1, 2, 17).

Microscopic characteristics
Lamina: The dorsiventral view reveals a fairly large and loosely packed
palisade layer of cells. Cells of the upper epidermis have straight to slightly
sinuous anticlinal walls, whereas the cells of the lower epidermis are more
wavy-walled. Anomocytic stomata on both surfaces, more numerous on
the lower surface, with covering trichomes scattered on the upper epider-
mis, especially over the veins, very abundant on the lower epidermis; indi-
vidual trichomes mostly of the whiplash type with several small cells form-
ing the uniseriate bases and very long, narrow and sinuous terminal cells
intertwining to form a felted mass covering the surface; other less numer-
ous, uniseriate covering trichomes composed of 4–6 cells, tapering to a
blunt apex with the cells sometimes more or less globular to ovoid; fairly
large glandular trichomes also abundant on both surfaces, with short, 1- or
2-celled stalk and a spherical head filled with a brownish secretion.
Midrib and petiole: Epidermal cells rectangular and longitudinally elon-
gated, with scattered glandular and covering trichomes similar to those in
the lamina. Transverse section shows bands of collenchyma below both
the upper and lower epidermises; a large vascular bundle in each ridge on
the lower surface, and a number of smaller bundles arranged in an arc sur-
rounding the groove on the upper surface; vascular bundles composed of
a dense group of pericyclic fibres with thick, lignified walls, a wide area of
thin-walled sieve tissue and a lignified xylem containing small vessels, tra-
cheids and xylem parenchyma; below each xylem group a mass of ligni-
fied fibres, which, in the larger bundles, extends as a narrow layer on
either side of the vascular tissue to join with the fibres of the pericycle;
ground tissue composed of large-celled, rounded parenchyma, some with
lignified walls (1, 2).

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Powdered plant material

Greyish-green to brown powder with faint odour; fragments of the lam-
ina with more or less sinuous walls and anomocytic stomata; covering
trichomes, scattered or in felted masses and large, glandular trichomes
with brown contents; groups of lignified fibres and vessels from the mid-
rib and petiole, the larger vessels with reticulate thickening (1, 2).

General identity tests

Macroscopic and microscopic examinations (1, 2, 17), and thin-layer
chromatography (1, 2).

Purity tests
Microbiological
Tests for specific microorganisms and microbial contamination limits are
as described in the WHO guidelines on assessing quality of herbal medi-
cines with reference to contaminants and residues (18).

Foreign organic matter

Not more than 2.0% (1, 2).

Total ash
Not more than 15.0% (1, 2).

Acid-insoluble ash
Not more than 4% (2).

Water-soluble extractive
Not less than 25.0% (2).

Loss on drying
Not more than 8% (1).

Pesticide residues
The recommended maximum limit of aldrin and dieldrin is not more than
0.05 mg/kg (19). For other pesticides, see the European pharmacopoeia (19)
and the WHO guidelines on assessing quality of herbal medicines with
reference to contaminants and residues (18) and pesticide residues (20).

Heavy metals
For maximum limits and analysis of heavy metals, consult the WHO
guidelines on assessing quality of herbal medicines with reference to con-
taminants and residues (18).

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Radioactive residues
Where applicable, consult the WHO guidelines on assessing quality of
herbal medicines with reference to contaminants and residues (18).

Other purity tests

Chemical tests to be established in accordance with national requirements.

Chemical assays
To be established in accordance with national requirements.

Major chemical constituents

Contains up to 6% phenolic acids, including 1-O-caffeoylquinic acid, 3-O-
caffeoylquinic acid (chlorogenic acid), caffeic acid, 4-O-caffeoylquinic acid,
5-O-caffeoylquinic acid, 1,5-di-O-caffeoylquinic acid (cynarin); up to 5% ses-
quiterpene lactones, with cynaropicrin being the primary component, followed
by dehydrocynaropicrin, grosheimin and their derivatives; and flavonoids
(0.35–0.75%) including scolymoside, cynaroside and cynarotrioside (7, 16, 17,
21). The structures of chlorogenic acid, caffeic acid, cynarin, cynaropicrin, sco-
lymoside, cynaroside A-L-rhamnopyranosyl and caffeoyl are presented below.

HO H O R3
HO
CO2H Chlorogenic acid R1 = R3 = H R2 = Caf
H
HO
R2 CO2H Cynarin R1 = R3 = Caf R2 = H
O
Caffeic acid H O R1
O OH
CH2 O OH
O CH2 R
H2C H HO O O
OH O
H OH
H H Cynaroside R=H
O
HO HO
H Scolymoside R = Rha
CH2 Cynaropicrin OH OH O

HO O
HO O
Rha = CH3
Caf = C
HO
OH OH

-L-rhamnopyranosyl Caffeoyl

Medicinal uses
Uses supported by clinical data
Treatment of digestive complaints (e.g. dyspepsia, feeling of fullness, flat-
ulence, nausea, stomach ache and vomiting) (15, 22, 23). Adjunct treat-
ment of mild to moderate hypercholesterolaemia (22, 24–27).

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Uses described in pharmacopoeias and well established documents

Orally for the treatment of atherosclerosis and kidney dysfunctions (di-
uretic) (5).
One study has indicated that the crude drug may be of benefit for the
treatment of irritable bowel syndrome (28), but further randomized con-
trolled clinical trials are needed before any therapeutic recommendations
can be made.

Uses described in traditional medicine

Oral treatment of anaemia, diabetes, fever, gout, rheumatism and urinary
stones (7, 9, 29).

Pharmacology
Experimental pharmacology
Antiatherosclerotic and antihypercholesterolaemic activities
A dried aqueous extract of the leaves (4.5:1) inhibited cholesterol biosyn-
thesis from 14C-acetate in primary cultured rat hepatocytes in a concentra-
tion-dependent biphasic manner with moderate inhibition (approximately
20%) being noted between 0.007 and 0.1 mg/ml and stronger inhibition at
1 mg/ml (80%). Replacement of 14C-acetate by 14C-mevalonate largely
prevented the inhibitory effects of the extracts, indicating inhibition of the
activity of hydroxyl-methyl-glutaryl-CoA-reductase. Stimulation of hy-
droxyl-methyl-glutaryl-CoA-reductase activity by insulin was efficiently
blocked by the extract. Cynaroside and its aglycone luteolin, constituents
of the extract, were mainly responsible for enzyme inhibition (30). The
effect of an extract of the leaves in vivo was investigated in four groups of
10 rats each fed an atherosclerogenic diet. Group one was administered
110 mg/kg body weight (bw) powdered leaves; group two, 80.0 mg/kg bw
powdered Cynara cardunculus; group three, 10.0 mg/kg bw heparaxal;
and group four served as the control. Examination of tissue after 120 days
showed that the leaf extract prevented formation of atherosclerotic chang-
es, prevented serum cholesterol increase, caused a decrease in lipid phos-
phate, slightly increased the level of glycoproteins in the blood, prevented
an increase in serum G-globulin, decreased albumin, glycoproteins and
liver cholesterol, and increased G-globulin and G-globulin fractions. Cy-
nara cardunculus showed a similar but weaker activity (31). A methanol
extract of the leaves was shown to reduce serum triglyceride levels in olive
oil-loaded mice. Oral administration of the extract, at doses between 125
and 500.0 mg/kg bw, significantly suppressed serum triglyceride elevation
2 h after administration of olive oil. In contrast, 6 h after administration of
olive oil, increases in triglyceride level were observed in the groups that

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received the extract at doses of 125.0 and 250.0 mg/kg bw. Orlistat, a li-
pase inhibitor, completely suppressed the serum triglyceride elevation at
250.0 mg/kg bw. Clofibrate, a hypolipidaemic medicine, also suppressed
the triglyceride level at doses of 250.0 and 500.0 mg/kg bw. Three sesqui-
terpenes (cynaropicrin, aguerin B and grosheimin) from the extract were
isolated as the active components (32).
Antihepatotoxic activity
The effects of an aqueous extract of the leaves on taurolithocholate-in-
duced cholestatic bile canalicular membrane distortions were studied in
primary cultured rat hepatocytes using electron microscopy. Artichoke
extracts at concentrations between 0.08 and 0.5 mg/ml were able to pre-
vent the formation of canalicular membrane transformations in a dose-
dependent manner when added simultaneously with the bile acid. How-
ever, prevention also occurred when the hepatocytes were preincubated
with the extracts, indicating that absorption of the bile acid to compo-
nents of the extracts was not involved (33).
The hepatoprotective activity of cynarin against carbon tetrachloride
(CCl4)-induced toxicity in isolated rat hepatocytes was compared with
other phenolic compounds. Only cynarin and, to a lesser extent, caffeic
acid showed a cytoprotective effect (34). Treatment of rats with three con-
secutive doses of 500.0 mg/kg bw of an extract of the crude drug, admin-
istered by gavage 48, 24 and 1 h before CCl4 intoxication, produced a
significant decrease in glutamic-oxaloacetic transaminase, glutamic-pyru-
vic transaminase (also known as alanine aminotransferase or ALT), direct
bilirubin and glutathione levels, thus indicating a reduction in the poten-
tial for hepatotoxicity (35).
Primary cultures of rat hepatocytes exposed to tert-butyl hydroperox-
ide were used for characterizing the antioxidative and hepatoprotective
potential of an aqueous extract of the crude drug and some selected con-
stituents. Addition of tert-butyl hydroperoxide to the culture media re-
sulted in enhanced lipid peroxidation as measured by the production of
malondialdehyde and enhanced cytotoxicity detected by leakage of lac-
tate dehydrogenase. The extract added prior to or simultaneously with
tert-butyl hydroperoxide reduced both phenomena with a median effec-
tive concentration (EC50) of 95.0 and 12.0 μg leaf powder/ml, respectively.
Furthermore, the aqueous extract prevented the loss of intracellular glu-
tathione caused by tert-butyl hydroperoxide. Several polyphenolic and
flavonoid constituents of the extract were found to reduce malondialde-
hyde production. The median effective concentration values were 8.1,
12.5, 15.2 and 28 μg/ml for caffeic acid, chlorogenic acid, cynarin and
cynaroside, respectively (36).

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Primary rat hepatocyte cultures exposed to tert-butyl hydroperoxide

or cumene hydroperoxide were used to assess the antioxidative and pro-
tective potential of aqueous extracts of the leaves. Both hydroperoxides
stimulated the production of malondialdehyde, particularly when the
cells were pretreated with diethylmaleate in order to diminish the level of
cellular glutathione. Addition of the extract did not affect basal malondi-
aldehyde production, but prevented the hydroperoxide-induced increase
of malondialdehyde formation in a concentration-dependent manner
when presented simultaneously with or prior to the peroxides. The effec-
tive concentrations were as low as 0.001 mg/ml (37).
Antioxidant activity
A study measured the effects of aqueous and ethanol extracts of the leaves
on intracellular oxidative stress stimulated by inflammatory mediators, tu-
mour necrosis factor alpha and oxidized low-density lipoprotein (ox-LDL)
in endothelial cells and monocytes. Both extracts inhibited basal and stim-
ulated reactive oxygen species production in endothelial cells and mono-
cytes, in a dose-dependent manner. In endothelial cells, the ethanol extract
(50.0 μg/ml) significantly reduced ox-LDL-induced intracellular reactive
oxygen species production by 60% (p < 0.001) and the aqueous extract
(50 μg/ml) reduced ox-LDL-induced intracellular reactive oxygen species
production by 43% (p < 0.01). The ethanol extract (50 μg/ml) reduced ox-
LDL-induced intracellular reactive oxygen species production in mono-
cytes by 76% (p < 0.01). Effective concentrations of 25–100 μg/ml were
well below the cytotoxic levels of the extracts which started at 1.0 mg/ml as
assessed by lactate dehydrogenase leakage and trypan blue exclusion (38).
An aqueous dried extract (9:2) of the leaves was studied in human
leukocytes to assess activity against oxidative stress. The extract (medi-
an effective concentration 0.23 μg/ml) produced a concentration-
dependent inhibition of oxidative stress when cells were stimulated with
agents that generate reactive oxygen species: hydrogen peroxide, phor-
bol-12-myristate-13-acetate and N-formyl-methionyl-leucyl-phenyl-
alanine. Cynarin, caffeic acid, chlorogenic acid and luteolin, constituents
of artichoke leaf extracts, also showed a concentration-dependent in-
hibitory activity in the above models, contributing to the antioxidant
activity of the extract in human neutrophils (39).
Choleretic effects
Two aqueous alcoholic extracts of the fresh leaves (total extract contain-
ing 19% caffeoylquinic acids, at a dose of 200.0 mg/kg bw and a semi-
purified extract containing 46% caffeoylquinic acids, at a dose of 25.0 mg/
kg bw) were assessed in rats. Intraperitoneal administration stimulated

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choleresis, and significantly increased bile dry residue and total cholate
secretion (p < 0.05). Intragastric administration of the same extracts
(400.0 mg/kg bw, total extract and 200.0 mg/kg bw of the semipurified
extract) also increased gastrointestinal motility by 11% and 14%, respec-
tively (p < 0.05) (40).
The effects of an extract of the crude drug on bile flow and the forma-
tion of bile compounds in anaesthetized rats after acute administration
and repeated oral administration (twice a day for 7 consecutive days) were
studied. A significant increase in bile flow was observed after acute treat-
ment with the extract as well as after repeated administration. The choler-
etic effects of the extract were similar to those of the reference compound
dehydrocholic acid. Total bile acids, cholesterol and phospholipid were
determined by enzymatic assays. At the highest dose (400.0 mg/kg bw), a
significant increase was observed after single and repeated administration
(p < 0.01) (41).
The choleretic effects of four extracts of the leaves (not described) were
assessed in vivo in a study in rats. Extracts 1, 2 and 4 did not show sig-
nificant choleretic activity at a dose of 1.0 and 2.0 g/kg bw. Extract 3,
however, was found to induce an increase of bile flow, which was gradual
and sustained. Cynarin and chlorogenic acid, administered as pure com-
pounds, did not show choleretic activity at any of the doses tested and
neither of them decreased the malondialdehyde content in liver (42).
Toxicology
The oral and intraperitoneal median lethal doses of a hydroalcoholic ex-
tract of the leaves in rats were 2.0 g/kg and 1.0 g/kg bw, respectively (40).
The oral median lethal dose of cynarin in mice was 1.9 g/kg bw. Intraperi-
toneal administration of cynarin to rats for 15 days, at doses between 50.0
and 400.0 mg/kg bw per day produced no macroscopic, haematological
or histological abnormalities. Intraperitoneal administration of cynarin to
rats for 40 days at a dose between 100.0 and 400.0 mg/kg bw per day in-
creased body and kidney weight, as well as producing some degenerative
changes in the liver (43). External application of a leaf extract to the skin
of white rats, at doses of 1.0–3.0 g/kg bw for 21 days, did not produce any
toxic effects or have any cumulative effects on haematological parameters
or the biochemistry of rats. No skin-irritating or eye-irritating effects
were observed in guinea-pigs (44).

Clinical pharmacology
Antidyspeptic effects
A multicentre open study assessed the effects of a dried aqueous leaf ex-
tract (3.8–5.5:1, 320 mg per capsule) in 553 patients with dyspeptic com-

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plaints. The daily dose was 4–6 capsules (containing 320.0 mg of extract
per capsule) per day, for an average of 43.5 days. Digestive complaints
declined significantly, by 71%, over the treatment period (p < 0.001).
Compared with the baseline data on subjective symptoms, a reduction in
abdominal pain (76%), emesis (88%), meteorism (66%) and nausea (82%)
was observed. In a subgroup of 302 patients, total cholesterol decreased
by 11.5% and triglycerides by 12.5% (25). In a similar study, the same
extract was assessed in a 6-month open trial involving 203 patients with
dyspepsia. The daily dose administered was 3–6 capsules (each capsule
containing 320.0 mg of the extract). After 21 weeks of treatment, symp-
toms such as vomiting, abdominal pain, nausea and flatulence decreased
by 84%, 78%, 77% and 70%, respectively. Total blood cholesterol and
triglycerides were reduced by 10.9% and 11%, respectively. Data from
159 patients indicated that low-density lipoprotein-cholesterol decreased
by 15.8% and high-density lipoprotein-cholesterol increased by 6.3%.
Global efficacy as assessed by physicians was good to excellent in 85.7%
of patients. No adverse reactions were reported (26).
In a double-blind, randomized controlled trial, 247 patients with func-
tional dyspepsia were treated with either a commercial extract of the crude
drug (2 × 320.0 mg of plant extract three times daily) or a placebo. The
primary outcome measured was the sum score of the patient’s weekly rat-
ing of the overall change in dyspeptic symptoms (four-point scale). Sec-
ondary variables were the scores for each dyspeptic symptom and the
quality of life as assessed by the Nepean Dyspepsia Index. Of the 247 pa-
tients enrolled, data from 244 patients (129 given active treatment, 115 giv-
en placebo) were suitable for inclusion in the statistical analysis (intention-
to-treat). The overall improvement in symptoms over the 6 weeks of
treatment was significantly greater in patients treated with the commercial
extract than in those treated with the placebo (8.3 ± 4.6 versus 6.7 ± 4.8,
p < 0.01). Similarly, patients treated with the commercial extract showed
significantly greater improvement in the global quality of life scores (Ne-
pean Dyspepsia Index) than the placebo-treated patients (-41.1 ± 47.6 ver-
sus -24.8 ± 35.6, p < 0.01). The preparation tested was significantly better
than the placebo at alleviating symptoms and improving the disease-
specific quality of life in patients with functional dyspepsia (45).
Antihypercholesterolaemic and lipid-lowering effects
Two randomized controlled clinical trials assessed the effects of a dried
aqueous extract of the leaves on cholesterol levels in 187 patients (24, 27).
The first, a randomized, double-blind, placebo-controlled pilot study in-
volving 44 healthy volunteers, assessed the effect of an extract of the crude
drug on cholesterol levels. Patients were randomly assigned to receive

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either 640.0 mg of the extract or a placebo three times daily for 12 weeks.
No significant effects on serum cholesterol were found. However in sub-
group analysis, significant cholesterol-lowering effects were observed in
subjects with a total cholesterol level of > 210 mg/dl (p < 0.022) (27).
The second placebo-controlled study assessed the safety and efficacy
of a dried aqueous extract of fresh artichoke (25–35:1). Patients received
either 1800 mg of artichoke extract as coated tablets, each containing
450.0 mg extract, or a placebo. Patients (n = 143) with hyperlipoprotein-
aemia – initial total cholesterol of > 7.3 mmol/l (> 280 mg/dl) received
1.8 g of a dried leaf extract per day or the placebo for 6 weeks. Changes in
total cholesterol and low-density lipoprotein-cholesterol from baseline to
the end of treatment showed a statistically significant superiority of the
dry artichoke extract over the placebo (p = 0.0001). Observed reductions
in total cholesterol levels were 18.5% in those who received the extract
and 8.6% in those who received the placebo after 6 weeks of treatment
(24). The decrease in low-density lipoprotein-cholesterol in the group
treated with the extract was 22.9% and was 63% in those treated with the
placebo. The ratio of low-density lipoprotein to high-density lipoprotein
showed a decrease of 20.2% in the group that received the extract and
7.2% in the group that received the placebo. No drug-related adverse
events were reported (24).
In a randomized, placebo-controlled clinical trial, two groups of 30 pa-
tients presenting various dislipidaemic profiles were treated for 50 days
with either cynarin, 2 × 250 mg tablets per day, or a placebo. Cynarin was
able to induce a significant reduction of hypercholesterolaemia (p < 0.001),
the level of pre-B-lipoproteins (p < 0.01), the B/A-lipoprotein ratio
(p < 0.01) and patient’s body weight (46).
Several uncontrolled studies have found that cynarin reduced total se-
rum cholesterol in patients after treatment with oral doses of 750–1500 mg
per day. Oral administration of cynarin to 17 patients, at a dose of 1000 mg/
day, for 4 weeks resulted in a significant decrease in total cholesterol (15%,
p < 0.005) (9).
Choleretic effect
A randomized, double-blind, placebo-controlled trial assessed the chol-
eretic effects of a dry aqueous extract of the leaves (4.5–5:1) in 20 male
volunteers with acute or chronic metabolic disorders. The treatment
group (n = 10) received a single intraduodenal dose of the extract at a dose
of 1.92 g/day in 50 ml of water on an empty stomach, while the control
group received a placebo of similar appearance. Crossover to the alterna-
tive treatment followed an 8-day washout period. The outcomes included
intraduodenal bile secretion measured using multi-channel probes. Com-

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pared with baseline values, 60 minutes after administration there was a

significant increase in bile secretion in the treatment group (151%) as
compared with the placebo group (p < 0.01) (23).
Irritable bowel syndrome
Irritable bowel syndrome, characterized by abdominal pain and altered
bowel habit, has symptoms that overlap with those of dyspepsia. Since
the crude drug is used for the treatment of dyspepsia, a postmarketing
surveillance study was performed to assess its effects on irritable bowel
syndrome. A subgroup of patients (n = 279) with symptoms of irritable
bowel syndrome was identified from a sample of individuals (n = 553)
with dyspeptic syndrome who were being monitored in a postmarketing
surveillance study of the extract for 6 weeks. Analysis of the data from the
subgroup with irritable bowel syndrome revealed significant reductions
in the severity of symptoms including abdominal pain, bloating, flatu-
lence and constipation, and favourable evaluations of overall effectiveness
by both physicians and patients (28).
Pharmacokinetics
A study to investigate the absorption, metabolism and disposition of arti-
choke leaf extract was performed using two different extracts (47). The
extracts were administered to 14 healthy volunteers in a crossover study.
Each subject received doses of both extracts. The administered dose of
extract A contained caffeoylquinic acids equivalent to 107.0 mg caffeic
acid and luteolin glycosides equivalent to 14.4 mg luteolin. The adminis-
tered dose of extract B contained caffeoylquinic acids equivalent to
153.8 mg caffeic acid and luteolin glycosides equivalent to 35.2 mg luteo-
lin. Urine and plasma analysis were performed by a validated high-per-
formance liquid chromatography method using 12-channel coulometric
array detection. None of the genuine target extract constituents could be
detected in the plasma or urine of the subjects. However, caffeic acid, its
methylated derivates ferulic acid and isoferulic acid and the hydrogena-
tion products dihydrocaffeic acid and dihydroferulic acid were identified
as metabolites derived from caffeoylquinic acids. Except for dihydrofer-
ulic acid, all of these compounds were present as sulfates or glucuronides.
Peak plasma concentrations of total caffeic acid, ferulic acid and isoferulic
acid were reached within 1 h and declined over 24 h showing almost bi-
phasic profiles. By contrast, maximum concentrations for total dihydro-
caffeic acid and dihydroferulic acid were observed only after 6–7 h, indi-
cating two different metabolic pathways for caffeoylquinic acids. Luteolin
administered as glucoside was recovered from plasma and urine only as
sulfate or glucuronide, but neither in the form of genuine glucosides nor

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as free luteolin. Peak plasma concentrations were reached rapidly within

0.5 h. The elimination showed a biphasic profile (47).

Adverse reactions
Gastrointestinal complaints included mild diarrhoea, accompanied by ab-
dominal cramps, upper abdominal pain, nausea and heartburn. Allergic
reactions may occur in sensitized patients (22, 25).
No significant adverse events other than gastrointestinal discomfort have
been reported from open or controlled clinical trials (24–27, 48).

Contraindications
Hypersensitivity or allergies to artichokes and other plants from the
Compositae/Asteraceae, and obstruction of the bile ducts (15).

Warnings
Possible interaction with coumarin-type anticoagulants.

Precautions
General
Patients with gallstones should seek the advice of a health care provider
prior to use.

Carcinogenesis, mutagenesis, impairment of fertility

The genotoxic effects of flavonoid constituents present in the crude drug
(quercetin and luteolin) were assessed in two short-term bacterial assays
(49). In Salmonella typhimurium (strains TA1538 uvrB- and TA1978
uvrB+) the flavonoids did not induce damage in the DNA as recognized
by UvrABC nuclease. Results of the SOS-chromotest in Escherichia coli
K-12 strains PQ37 and PQ243 indicated that the flavonoids only weakly
induced the SOS system (49).

Drug interactions
No information was found.1

Pregnancy: teratogenic effects

Due to the lack of safety and efficacy studies, the use of the crude drug
during pregnancy is not recommended.

1
A report of a potential drug interaction with Folium Cynarae or its preparations and with couma-
rin-type anticoagulants such as phenprocoumone and warfarin has been recorded by a national
regulatory authority.

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Pregnancy: non-teratogenic effects

Due to the lack of safety data, the use of the crude drug during pregnancy
is not recommended.

Nursing mothers
Due to the lack of safety data, the use of the crude drug during breastfeed-
ing is not recommended.

Paediatric use
Due to the lack of safety data, the use of the crude drug for the treatment
of children under the age of 12 years is not recommended.

Other precautions
No information was found.

Dosage forms
Crude drug, extracts and other Galenical preparations for internal use.

Posology
(Unless otherwise indicated)
Average oral daily dose: for hypercholesterolaemia and dyspepsia, 1–2 g
of a dried aqueous extract (24, 27, 45). Adult daily dose: 5–10 g of crude
drug; or equivalent preparations (15, 17).

References
1. Pharmacopée Francaise [French pharmacopoeia]. Paris, Adrapharm, 1987.
2. British herbal pharmacopoeia. Exeter, British Herbal Medicine Association,
1996.
3. Reynolds JEF, ed. Martindale: The extra pharmacopoeia, 13th ed. London,
Pharmaceutical Press, 1993.
4. PharmaMed: Aufbereitungsmonographien (Kommission E CD-ROM). Stut-
tgart, Deutscher Apotheker Verlag, 2004.
5. African pharmacopoeia, Vol. 1, 1st ed. Lagos, Nigeria, Organization of Afri-
can Unity, Scientific Technical & Research Commission, 1985.
6. National Genetic Resources Program. Germplasm Resources Information
Network (GRIN) [Online Database]. Beltsville, Maryland, National Germ-
plasm Resources Laboratory (available at: http://www.ars-grin.gov2/cgi-
bin/npgs/html/tax_search.pl?cynara+scolymus).
7. Farnsworth NR, ed. NAPRALERT database. Chicago, University of Illinois
at Chicago, IL (an online database available directly through the University
of Illinois at Chicago or through the Scientific and Technical Network [STN]
of Chemical Abstracts Services), 30 June 2005.

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8. Nadkarni KM, Nadkarni AK, eds. Indian materia medica, reprint of 3rd re-
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