Journal of Ethnopharmacology 110 (2007) 458–463

Diuretic activity of the aqueous extracts of Carum carvi

and Tanacetum vulgare in normal rats
Sanaa Lahlou a , Adil Tahraoui a , Zafar Israili b , Badiaâ Lyoussi a,∗
a UFR Physiology-Pharmacology, Laboratory of Animal Physiology, Department of Biology,
Faculty of Sciences Dhar El Mehraz, Fez, Morocco
b Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA

Received 17 February 2006; received in revised form 10 October 2006; accepted 12 October 2006
Available online 19 October 2006

Abstract
In the Moroccan traditional medicine, the ripe fruits of Carum carvi L. (Apiaceae) and the leaves of Tanacetum vulgare L. (Aster-
aceae/Compositae), two widely available plant materials, are used as diuretics. Since, the diuretic activity of these substances has not been
investigated in scientifically controlled studies, the aim of the present study was to evaluate the diuretic potential of aqueous extracts of Carum
carvi fruit (caraway) and the leaves of Tanacetum vulgare (tansy) in normal rats after acute and sub-chronic oral administration. Water extracts
of Carum carvi and Tanacetum vulgare (100 mg/kg) or the reference drug, furosemide (10 mg/kg) were administrated orally to male Wistar rats
and their urine output was quantitated at several intervals of time after the dose. After single doses of the extracts of both caraway seeds and tansy
leaves, urine output was significantly increased at all time points, and at 24 h after the dose, the total volume of urine excreted was similar for
the plant extracts and furosemide. Both extracts increased urinary levels of Na+ and K+ , to about the same extent, while furosemide increased
urinary levels of only Na+ and decreased urinary K+ . Despite changes in urinary excretion of the electrolytes, plasma Na+ and K+ levels were not
affected by any of the three substances. In the 8-day sub-chronic study, all three substances induced significant diuresis and natriuresis; only tansy
increased urinary potassium excretion. The plant extracts did not appear to have renal toxicity or any other adverse effects during the study period.
In conclusion, water extracts of both Carum carvi and Tanacetum vulgare have strong diuretic action confirming their ethnopharmacological use.
From the pattern of excretion of water, sodium and potassium, it may be deduced that there are atleast two types of active principals present in
these extracts, one having a furosemide-like activity and the other a thiazide-like activity.
© 2006 Published by Elsevier Ireland Ltd.

Keywords: Carum carvi L.; Tanacetum vulgare L.; Caraway; Tansy; Diuretic activity; Urine output; Aqueous extract; Apiaceae; Asteraceae/Compositae

1. Introduction found to be effective against spasmodic gastrointestinal

Plant medicine is commonly used in the traditional treatment
of some renal diseases, and many plants are reported to possess
significant diuretic activity (Bellakhdar, 1997; Maksimovic et
al., 2004; Tanira et al., 1988). The diuretic activity of a number
of plants used in ethnomedicine as diuretic agents has been
confirmed in experimental animals (Benjumea et al., 2005;
Maksimovic et al., 2004).
The dried ripe fruits of Carum carvi L. Apiaceae (Umbel-
liferae) (caraway) are used in folk medicine as a carminative,
∗ Corresponding author at: UFR Physiology-Pharmacology, Université Sidi
Mohamed Ben Abdellah, Faculté des Sciences Dhar El Mehraz, Morocco.
Fax: +212 55733059.
E-mail address: lyoussi@rocketmail.com (B. Lyoussi).
complaints, flatulence, irritable stomach, indigestion, lack
of appetite, and dyspepsia in adults (Holtmann et al., 2003;
Madisch et al., 2004; Thompson Coon and Ernst, 2002), and in
relieving flatulent colic of infants (Reynolds, 1993). In Moroc-
can traditional medicine, an aqueous extract of caraway is used
as an aperitif, tranquilizer, carminative, diuretic, emenagogue,
galactagogue, spasmolytic, gastric stimulant and as an aphro-
disiac (Bellakhdar, 1997). The plant extract and the volatile oils
from Carum carvi have also been used as an antiulcerogenic
agent (Khayyal et al., 2001). Furthermore, experimental studies
have shown its antitumor (Zheng et al., 1992), antiproliferative
(Nakano et al., 1998), antihyperglycemic (Eddouks et al.,
2004), and antimicrobial (Iacobellis et al., 2005) activities.
Tanacetum vulgare L. (tansy), an herbaceous plant belong-
ing to the family of Asteraceae/Compositae, is found world-

0378-8741/$ – see front matter © 2006 Published by Elsevier Ireland Ltd.

doi:10.1016/j.jep.2006.10.005
 S. Lahlou et al. / Journal of Ethnopharmacology 110 (2007) 458–463
wide (Keskitalo et al., 1998; Global Compendium of Weeds
home page, http://www.hear.org/gcw/html/index.html, accessed
February 2006). In folk medicine, tansy has been used as
panacea for diverse health problems, such as an anthelminthic,
carminative, antispasmodic, abdominal viscera stimulant, tonic,
emenagogue, antidiabetic, diuretic and antihypertensive agent.
Aqueous extracts of tansy have been reported to exhibit antiin-
flammatory (Williams et al., 1999), antioxidant (Bandoniene et
al., 2000), antimicrobial (Holopainen and Kauppinen, 1989) and
hypoglycemic (Takagi, 2002) activities. It has also been reported
to have a healing effect on experimental gastric ulcer (Tournier
et al., 1999). Furthermore, it has been shown that tansy extract
is used in a treatment of increased bone resorption (Muehlbauer,
2002).
Diuretics, either alone or in combination with other drugs,
are valuable in the treatment of hypertension, congestive heart
failure, ascites, and pulmonary edema (Gupta and Neyses, 2005;
Hughes, 2004; Jackson, 1996; Morganti, 2005; O’Brien et al.,
2005). Two widely used diuretics, thiazides and the high ceiling
loop diuretic, furosemide, have been associated with a num-
ber of adverse effects, such as, electrolyte imbalance, metabolic
alterations, development of new-onset diabetes, activation of the
rennin–angiotensin–neuroendocrine systems, and impairment
of sexual function (Gupta and Neyses, 2005; Morganti, 2005).
Hence, there is a need for new diuretics with lower potential for
adverse effects, such as the plant-based substances which are
considered to be relatively safe.
Although, both caraway and tansy are well recognised in
Moroccan traditional medicine as having a diuretic effect at a
dose of 100 mg/kg, no scientific data have been published sup-
porting the claimed ethnomedical use. Therefore, the aim of
this study was to evaluate the acute and sub-chronic diuretic,
saliuretic, and kaliuretic effects of orally administered aqueous
extracts of caraway seeds and tansy leaves in normal rats and
thus, to confirm their ethnomedical use.
2. Materials and methods
2.1. Experimental animals
Adult male Wistar rats weighing between 150 and 200 g
procured from our animal house were housed under standard
environmental conditions (25 ± 1 ◦ C, 55 ± 5% humidity and
12 h/12 h light/dark cycle). The animals were allowed free access
to tap water and standard laboratory rat food. The care and han-
dling of rats were in accordance with the internationally accepted
standard guidelines for use of animals, and the protocol was
approved by our institutional committee on animal care follow-
ing the French Technical Specifications for the Production, Care
and Use of the Laboratory Animals.
2.2. Plant material and preparation of the extracts
The ripe fruits of the common caraway [Carum carvi L.
(Asteraceae)] were collected from the Fes region and tansy
leaves from the Marrakech region in Morocco. Tansy was iden-
tified as Tanacetum vulgare L. (Asteraceae/Compositae) by
459
Professor Bel Kamel, Faculté des Siences Techniques (F.S.T.,
Marrakech, Morocco). Both caraway fruits and tansy leaves
were dried at room temperature in the shade, and then ground
in an electric grinder to give a coarse powder.
Fifty grams of the dried powder of caraway fruits was mixed
with 500 mL of water, and the mixture was boiled at 100 ◦ C
under reflux for 30 min. The decoction obtained was centrifuged,
filtered, frozen at −20 ◦ C, and then lyophilised (FreeZone® Dry
4.5, USA), yielding approximately 13.6% (w/w) of dry extract of
Carum carvi L. The same procedure was used to extract tansy
leaves (50 g dry powder extracted with 500 mL of water); the
yield of the product was approximately 13.5% (w/w) of the dry
leaves of Tanacetum vulgare L.
For each study, the lyophilized aqueous extract was carefully
prepared under the same conditions used throughout the studies
(time, temperature and the amount of plant material and water
used for extraction under reflux, and lyophilization), and each
time the quality of extraction was checked by the yield of the
lyophilized material. For assuring stability, the lyophilized mate-
rial was stored at −20 ◦ C until used. The two lyophilized prod-
ucts (caraway and tansy) were dissolved in water (10 mg/mL)
before administration at the stated doses.
2.3. Reference drug
Furosemide (Lasilix, Pharma 5, Morocco), a high-ceiling
loop diuretic, was used as the reference drug (positive control).
It was dissolved in water prior to administration.
2.4. Biochemical methods
Blood was collected in capillary tubes containing ethylene-
diamine tetraacetic acid by retro-orbital puncture under light
diethyl ether anesthesia. Plasma was obtained by centrifugation
(600 × g at 4 ◦ C), and stored at −20 ◦ C until analyzed. Plasma
and urinary levels of sodium and potassium were quantitated by
flame spectrophotometry. Concentration of creatinine in plasma
and urine was determined by the Jaffe alkaline picrate method.
Creatinine clearance, as a measure of renal function, was calcu-
lated from plasma and urinary creatinine levels.
2.5. Assessment of diuretic activity: experimental design
The diuretic activity was evaluated as follows: each animal
was placed in an individual metabolic cage 24 h prior to com-
mencement of the experiment for adaptation. The animals were
divided into four groups of five rats each for the acute (single
dose) study and another four groups of five rats each for the
sub-chronic (repeated dose) study. Rats were fasted overnight
with free access to water, and subjected to the stated treatment
as described below. The rats were observed occasionally for
apparent toxicity.
2.5.1. Acute diuretic activity
Before treatment, all animals received physiological saline
(0.9% NaCl) at an oral dose of 5 mL/100 g body weight (BW),
to impose a uniform water and salt load (Benjumea et al., 2005).
460 S. Lahlou et al. / Journal of Ethnopharmacology 110 (2007) 458–463
The first group received orally distilled water 10 mL/kg BW, and
served as the control group. The second and third groups were
administered orally 100 mg/kg BW of caraway fruit extract and
tansy leaf extract, respectively. The fourth group was treated
with an oral dose of 10 mg/kg BW of furosemide. Urine was
collected and measured at 1, 2, 4, 6, and 24 h after the dose.
Sodium and potassium concentrations were determined in the
24 h urine samples as well as in the plasma of rats.
2.5.2. Chronic diuretic activity
Daily oral doses of caraway fruit extract (100 mg/kg BW),
tansy leaf extract (100 mg/kg BW), and furosemide (10 mg/kg
BW) were administered to three groups of rats for 8 days; the
control animals received water (10 mL/kg) every day. For each
rat, 24 h urine was collected daily and its volume measured.
Urinary sodium and potassium concentrations were measured in
each urine specimen. Sodium, potassium and creatinine levels
were measured in plasma of rats on Day 8. Urinary creatinine
excretion was also determined and its clearance was calculated
for Day 8. The rats were observed daily for apparent toxicity.
2.6. Statistical analysis
Results are expressed as mean ± S.E.M. Statistical analysis
of the data was performed with one-way analysis of variance
(ANOVA) (Graph Pad Prism version 3.00, USA) or by Student’s
t-test. Significant differences were indicated by P values lower
than 0.05.
3. Results
3.1. Diuretic activity of a single dose of the plant extracts
and furosemide
3.1.1. Effect on urine volume
Treatment with a single dose of the caraway extract increased
diuresis (Fig. 1), which became significantly higher than in the
control rats at 4 h after the dose (caraway 5.7 ± 0.3 mL versus
controls 3 ± 0.5 mL; P < 0.05). Urine output continued to be
Fig. 1. Acute diuretic effect: diuretic activities of single oral doses (100 mg/kg
BW) of aqueous extracts of Carum carvi L. seeds, Tanacetum vulgare L. leaves,
and furosemide (10 mg/kg BW). The volume of excreted urine was measured
at 1, 2, 4, 6 and 24 h after the treatment; cumulative values are reported as
mean ± S.E.M. for five rats in each group. * P < 0.05; ** P < 0.01; *** P < 0.001
compared with controls using Student’s t-test.
stimulated throughout the study period, such that the cumulative
urinary excretion was significantly higher at 6 and 24 h after the
dose of the caraway extract compared to the controls (caraway
12.8 ± 0.1 mL versus controls 7.7 ± 0.7 mL at 24 h after dose;
P < 0.01) (Fig. 1).
The effect of a single dose of tansy extract was more rapid
and slightly higher than that of caraway extract (Fig. 1). The
effect became significantly higher at 1 h after the dose com-
pared to controls (tansy 4.0 ± 0.6 mL versus 0.7 ± 0.1 mL for
controls; P < 0.05). The diuretic effect remained significantly
higher for the tansy-treated rats as compared to control rats at
all time points (Fig. 1), such that the cumulative 24 h urinary
excretion for the tansy-treated rats was 14.3 ± 0.4 mL as com-
pared to 7.7 ± 0.7 mL (P < 0.01) for the controls.
The effect of a single dose of the reference diuretic,
furosemide, was also rapid and higher than that of the plant
extracts (Fig. 1), however, the 24 h cumulative urinary excre-
tion was not too different for the three substances (car-
away 12.8 ± 0.1 mL, tansy 14.3 ± 0.4 mL, and furosemide
18.5 ± 0.6 mL).
3.1.2. Effect on urinary electrolyte excretion
The effect of single doses of furosemide and the aqueous
extracts of caraway and tansy on electrolyte (Na+ and K+ ) excre-
tion in the 24 h urine is presented in Table 1. Both plant extracts
enhanced the excretion of the electrolytes [Na+ (P < 0.001) and
K+ (P < 0.05)], which was greater than produced by furosemide,
especially that of K+ . Furosemide actually decreased K+ excre-
tion as compared to the controls, such that the Na+ /K+ excretion
ratio (2.51) was higher than for the plant extracts (caraway 1.85,
tansy 1.88) (Table 1).
3.1.3. Effect on plasma electrolyte levels
There was no effect of any of the three substances,
furosemide, caraway and tansy extracts on plasma levels of Na+
and K+ (Table 1).
3.2. Diuretic activity of the plant extracts and furosemide
after sub-chronic administration
3.2.1. Effect on urine volume
Administration of daily doses of both caraway and
tansy extracts produced significant diuresis starting on
Day 1 (caraway 9.3 mL ± 1.2; tansy 9 mL ± 0.6; controls
5.4 mL ± 0.7; P < 0.05), which became increasingly significant
until Day 6 (caraway 20.2 mL ± 0.4; tansy 23 mL ± 1.6; con-
trols 5.8 mL ± 1.0; P < 0.001), after that urinary output levelled
off (Fig. 2). The diuretic effect of furosemide was initially higher
than produced by the plant extracts, and then it was similar to
that of the plant extracts after Day 4 (Fig. 2).
3.2.2. Effect on urinary electrolyte excretion
Both plant extracts (caraway and tansy) significantly induced
urinary excretion of Na+ (P < 0.01) starting on Day 4, which
became more pronounced (P < 0.001) from Day 5 to Day 8. The
excretion of K+ increased significantly (P < 0.01) throughout
the treatment [with maximum effect (P < 0.001) from Day 4 to
 S. Lahlou et al. / Journal of Ethnopharmacology 110 (2007) 458–463 461

Table 1
Effect of a single oral dose of the aqueous extracts of caraway and tansy, and furosemide on 24 h urinary electrolyte excretion and plasma Na+ and K+ levels in
normal rats
Treatmenta Dose (mg/kg BW) Urinary electrolyte concentration Plasma electrolyte level

Na+ (mmol/L) K+ (mmol/L) Na+ (mmol/L) K+ (mmol/L)

Water, 10 mL/kg BW (control) 89.7 ± 1.8 62.9 ± 1.1 145.7 ± 1.2 5.3 ± 0.4
Furosemide 10 127.7 ± 1.5** 50.8 ± 0.9** 147.5 ± 1.6 5.1 ± 0.3
Carum carvi extract 100 138.7 ± 1.5*** 75.0 ± 2.0* 142.3 ± 1.3 5.8 ± 0.3
Tanacetum vulgare extract 100 148.0 ± 1.7*** 78.4 ± 1.8* 143.3 ± 1.6 5.2 ± 0.5

Values are expressed as mean ± S.E.M. of five rats in each group. * P < 0.05; ** P < 0.01; *** P < 0.001 compared to controls using Student’s t-test.
a All rats were pre-treated with an oral dose of 5 mL/100 g BW of normal saline prior to the administration of the test substances.

Day 8], by the tansy extract, but not by the caraway extract or
furosemide (Fig. 4).
3.2.3. Effect on plasma electrolyte levels
As was the case with the acute dose, there was no effect
of sub-chronic administration of any of the three substances,
furosemide [Na+ (149.2 mmol/L ± 1.3) and K+ (5.2 mmol/
L ± 0.3)], caraway [Na+ (147.1 mmol/L ± 0.8) and K+
(5.6 mmol/L ± 0.7)] and tansy extracts [Na+ (147.3 mmol/
L ± 0.6) and K+ (6.3 mmol/L ± 0.5)] on plasma levels of Na+
and K+ .
3.2.4. Effect on creatinine clearance
Creatinine clearance, measured on the last day of treat-
ment, was not affected by any of the treatments (caraway
2.97 mL/min ± 0.11; tansy 3.37 mL/min ± 0.18; furosemide
2.48 mL/min ± 0.09; controls 3.13 mL/min ± 0.06).
4. Discussion and conclusions
In the present study, the diuretic effect of orally adminis-
tered aqueous extracts of caraway fruit and tansy leaves was
evaluated in normal rats after one dose and after daily dosing
for 8 days. The pharmacological response was compared with
that produced by furosemide, a widely used diuretic in clin-
Fig. 2. Sub-chronic diuretic effect: diuretic activities of daily oral doses
(100 mg/kg BW) of aqueous extracts of Carum carvi L. seeds, Tanacetum vul-
gare L. leaves, and furosemide (10 mg/kg BW) administered for 8 days. The
volume of 24 h urine was measured on Days 1 through 8 of treatment and
reported as mean ± S.E.M. for five rats in each group. * P < 0.05; ** P < 0.01;
*** P < 0.001 compared with controls using Student’s t-test.
ical practice. The two plant materials selected for the study,
caraway fruits and tansy leaves, are commonly available and
used in Moroccan traditional medicine to induce diuresis. Oral
route was chosen because that is the way people use these plants
in traditional medicine. The effect on electrolyte balance and
creatinine clearance was also determined. The mechanism of
action by which diuresis was induced by these two extracts was
also assessed by comparing the effect with that of furosemide,
a high-ceiling loop diuretic (Jackson, 1996), and that of
hydrochlorothiazide (from published reports; Benjumea et al.,
2005).
Diuresis has two components: increase in urine volume
(water excretion) and a net loss of solutes (i.e. electrolytes)
in the urine (Jackson, 1996). These processes result from sup-
pression of renal tubular reabsorption of water and electrolytes
into the blood stream. The reference drug, furosemide, increases
urine output and urinary excretion of sodium by inhibiting
Na+ /K+ /2Cl− symporter (co-transporter system) in the thick
ascending limb of the Loop of Henley (Jackson, 1996), while the
thiazide diuretics inhibit the Na+ /Cl− symporter (co-transporter
system) in the distal convoluted tubule, by competing for the
Cl− binding site, and increasing the excretion of Na+ and Cl−
(Jackson, 1996).
In the saline primed rats, a dose of the tansy extract caused a
significant increase in urine output beginning from the first hour
while the caraway extract took 4 h after the dose to increase urine
output significantly. In comparison, a single dose of furosemide
induced a brisk and significant diuresis within 60 min of admin-
istration (Fig. 1). The difference in the time of onset of the
diuretic action of these substances may be related to the gas-
trointestinal absorption characteristics of the active principle(s).
Stimulation of diuresis by single doses of all three substances
continued for atleast 24 h (Fig. 1).
Both caraway and tansy extracts induced significant increases
in urinary excretion of Na+ (154% and 164% of controls, respec-
tively) and to a lesser extent of K+ (119% and 123% of controls,
respectively); furosemide increased Na+ excretion (142% of
controls) but not that of K+ : actually there was a small decrease
in urinary concentration of K+ . Hydrochlorothiazide has been
reported to increase the urinary excretion of both Na+ and K+
by 50–60% over controls after a single oral dose in normal rats
(Benjumea et al., 2005). In this respect, the two plant extracts
appear to have several active components, with atleast one hav-
ing a mechanism of natriuresis similar to that of the thiazide
462 S. Lahlou et al. / Journal of Ethnopharmacology 110 (2007) 458–463

Fig. 3. Sub-chronic natriuretic activity: effect of daily oral doses (100 mg/kg
BW) of aqueous extracts of Carum carvi L. seeds, Tanacetum vulgare L. leaves,
and furosemide (10 mg/kg BW) administered for 8 days on urinary excretion of
Na+ . The reported Na+ levels (mean ± S.E.M.) are in pooled 24 h urine for each
day for each group of five rats each group. * P < 0.05; ** P < 0.01; *** P < 0.001
compared with controls using Student’s t-test.
Fig. 4. Sub-chronic kaliuretic activity: effect of daily oral doses (100 mg/kg
BW) of aqueous extracts of Carum carvi L. seeds, Tanacetum vulgare L. leaves,
and furosemide (10 mg/kg BW) administered for 8 days on urinary excretion of
K+ . The reported K+ levels (mean ± S.E.M.) are in pooled 24 h urine for each
day for each group of five rats each group. * P < 0.05; ** P < 0.01; *** P < 0.001
compared with controls using Student’s t-test.

studies have to be carried out to confirm the lack of renal toxic-

diuretic, and another with a mechanism of kaliuresis similar to
ity and to rule out other organ toxicity, especially after chronic
that of furosemide.
administration.
In the sub-chronic study, all three substances, furosemide and
A number of compounds have been identified in caraway,
caraway and tansy water extracts, induced significant diuresis
including carvone and other monoterpenoids and their glu-
from Day 1 (without priming with saline); urine output con-
cosides (Zheng et al., 1992), menthanetriols and glucosides
tinued to increase until Day 5 (maximum effect), after that it
(Matsumura et al., 2001), and limonene (Zheng et al., 1992),
stayed stable until the last day of the study (Fig. 2). Although,
and in tansy, such as flavonoids (Williams et al., 1999), mono-
the effect of furosemide was initially greater than that of the
, tri-, and sesqui-terpine lactones, and isoprenoids (Chandler
plant extracts, the 24 h urine output became similar for the three
et al., 1982; Umlauf et al., 2004), saponins, polyphenols, and
substances after Day 6, indicating that all the three substances
plant sterols (Chandler et al., 1982), parthenolide (Tournier et al.,
had reached their maximum effect. Tolerance does not seem to
1999), polysaccharides (Polle et al., 2002), thujones (Dragland
develop to the diuresis stimulating activity of the plant extracts.
et al., 2005), and chrysanthenyl analogs (Umlauf et al., 2004).
The plant extracts and furosemide did not influence urinary
At present, it is not known which compounds are responsible
excretion of Na+ for the first 2–3 days of repeated administra-
for the diuretic, natriuretic and kaliuretic activities of caraway
tion in these rats, which were not primed with saline (Fig. 3),
and tansy.
probably because of homeostasis mechanisms. After that period,
In conclusion, the present studies support the ethnomedical
repeated administration of all three substances caused signifi-
use of both caraway and tansy for their diuretic effect. The plant
cant increase (by overcoming the homeostasis mechanisms) in
extracts do not seem to have renal toxicity in rats at the dose
saliuresis (Fig. 2). On the other hand, repeated administration
studied. Although, the active components remain unidentified,
of furosemide and caraway extract virtually had no effect on
based on the pattern of excretion of water, sodium and potassium,
urinary K+ excretion for the entire 8 days. Contrarily, tansy
it appears that that there are atleast two types of active principals
extract caused a significant increase in urinary excretion of
present in these extracts, one having a furosemide-like activity
K+ beginning on Day 1 and continuing throughout the study
and the other a thiazide-like activity. These findings suggest, for
period.
the first time, mechanism(s) of diuretic action of caraway and
The results of the present studies suggest that the effect of
tansy used in traditional medicine by the Moroccan population.
one or more of the active components of caraway on electrolyte
excretion is furosemide-like, while the active substance(s) in
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