Antidiarrheal Activity of Laurus nobilis L. Leaf Extract in Rats
Esam Y. Qnais,
Fuad A. Abdulla,
Eziden G. Kaddumi,
and Shtaywy S. Abdalla
Department of Biology and Biotechnology, Faculty of Science;
Department of Medical Laboratory Sciences,
Faculty of Allied Health; Hashemite University, Zarka, Jordan.
Department of Physical Therapy, School of Health Professions, Behavioral
and Life Sciences, New York Institute of Technology, Amman, Jordan.
Department of Biological Sciences, Faculty of Science, University of Jordan, Amman, Jordan.
ABSTRACT In Jordan, the leaves of Laurus nobilis (Family Lauraceae) have been used in folk medicine for the treatment
of diarrhea, among other ailments. However, the ethnopharmacology of this plant needs to be scientiﬁcally validated. The
present work was carried out to evaluate the scientiﬁc basis of the antidiarrheal effect of the aqueous extract of L. nobilis leaf.
L. nobilis leaf extract signiﬁcantly inhibited castor oil–induced diarrhea (effective concentration producing 50% of the
maximum response [EC
]=150 –6.4 mg/kg) and reduced castor oil–induced enteropooling in rats (EC
=162 –5.9 mg/kg).
The extract also signiﬁcantly inhibited intestinal transit of a charcoal meal and exerted a signiﬁcant dose-dependent relaxation
=71 –5.3 mg/mL) on rat ileal smooth muscle. The aqueous extract tested positive for ﬂavonoids, alkaloids, and tannins.
These results established the efﬁcacy of L. nobilis leaf aqueous extract as an antidiarrheal agent and are consistent with the
popular use of the plant in the treatment of gastrointestinal disorders, particularly diarrhea.
KEY WORDS: antidiarrheal effect castor oil–induced diarrhea charcoal meal enteropooling intestinal motility
Diarrhea is characterized by excessive defecation,
wet stool output, and abdominal pain. It is a leading
cause of malnutrition and death among children in the de-
veloping countries of the world today.
for more than 2–8 million deaths each year in infants and
children less than 5 years old.
Several pharmaceutical agents are available for the
treatment and management of both adult and infantile di-
arrhea. In recent years, emphasis has focused on the use of
oral rehydration solutions as a replacement therapy to re-
plenish the lost ﬂuid and electrolytes in diarrheic cases.
However, there is still a need for continuing search for more
effective antidiarrheal agents with minimal side effects.
Laurus nobilis belongs to the Lauraceae family and is
commonly known as sweet bay but locally known as Al-
Ghar. It is an evergreen tree that can reach up to 8 m in
height and is native to Mediterranean regions. L. nobilis,a
dioecious plant, has been cultivated since ancient times, and
the aromatic, dark green, leathery leaves of the laurel tree
were used by ancient Greeks and Romans to crown their
L. nobilis is a plant of industrial importance be-
cause it is used in foods, drugs, and cosmetics. The dried
leaves and essential oils are used extensively in the food
industry for seasoning of meat products, soups, and ﬁshes.
The essential oil is also used as a folk medicine, especially
for the treatment of rheumatism and dermatitis.
L. nobilis has a long history of folk use in the treatment of
many ailments, particularly as an aid to digestion, to treat
bronchitis and inﬂuenza,
and to treat various types of
The leaves were reported to treat upper respiratory
tract disorders and to ease arthritic aches and pains.
studies have shown that L. nobilis seed and leaf essential oils
have gastroprotective, antinociceptive, and anti-inﬂamma-
They also have antidiabetic, cytotoxic, and
The essential oil and some
isolated compounds from L. nobilis have narcotic, antibac-
terial, and fungicidal properties.
Because of its anti-
microbial and fungicidal activities, L. nobilis is used in the
food industry as a food preservative.
Some phytochemical constituents of L. nobilis have been
isolated and identiﬁed. These include guaianolides, dehy-
drocostus lactone, zaluzanin D, p-menthane hydroperoxide,
peroxy radical scavenging compounds, sabinene, eugenol,
megastigmane glucosides, phenolic glucoside, sesquiter-
(E)-b-ocimene, 1,8-cineole, a-pinene, b-long-
ipinene, linalool acetate, cadinene, b-pinene, a-terpinyl
Manuscript received 3 April 2011. Revision accepted 27 July 2011.
Address correspondence to: Esam Y. Qnais, Department of Biology and Biotechnology,
Faculty of Science, Hashemite University, P.O. Box 150459, Zarka, Jordan, 13115,
JOURNAL OF MEDICINAL FOOD
J Med Food 15 (1) 2012, 51–57
#Mary Ann Liebert, Inc. and Korean Society of Food Science and Nutrition
coumaroyl)-rhamnoside (C2), and kaempferol 3-O-a-L-(2†-
In Jordan, L. nobilis is commonly used as a food spice,
and the leaf aqueous extract is widely used in the treat-
ment of hypertension, general weakness, arthritis, hair loss,
Despite the relatively wide use of this plant
in folk medicine, the scientiﬁc basis for its use as an an-
tidiarrheal drug has not been validated. The present study
was undertaken to evaluate the antidiarrheal effect of leaf
aqueous extract of L. nobilis, using castor oil–induced
diarrhea, enteropooling, intestinal transit time, and iso-
metric recording of ileal smooth muscle tone models.
MATERIALS AND METHODS
Fresh leaves of L. nobilis were collected from the Hash-
emite University campus (Al-Hashemia, Zarka, Jordan)
during April 2008. The plant material was identiﬁed and
authenticated taxonomically at the herbarium of Hashemite
University. A voucher specimen has been deposited there
for future reference under the number HU-394.
Preparation of aqueous extract
Aqueous extract was obtained by boiling 150 g of the
ground air-dried leaves of L. nobilis in 3 L of distilled water
for 15 minutes with continuous stirring. The resultant so-
lution was ﬁltered through Whatman (Maidstone, United
Kingdom) ﬁlter paper. The ﬁltrate was completely evapo-
rated under reduced pressure at 55C. Solutions were pre-
pared by dissolving the gummy residue in physiological salt
The aqueous extract (50 g/L) of the plant was subjected to
qualitative chemical screening for the detection of tannins,
alkaloids, and ﬂavonoids using standard procedures.
addition to the speciﬁc tests noted below, the presence of
these constituents was also conﬁrmed by thin-layer chro-
matography using different solvent systems, detecting re-
agents, and ultraviolet.
Test for tannins. One milliliter of aqueous extract was
mixed with 10 mL of distilled water and ﬁltered. Ferric
chloride reagent (3 drops) was added to the ﬁltrate. A blue–
black or green precipitate conﬁrmed the presence of gallic
tannins or catechol tannins, respectively.
Test for alkaloids. A mixture of 0.2 mL of aqueous
extract and 1% aqueous hydrochloric acid (5 mL) was
placed on a steam bath and then ﬁltered. One milliliter of the
ﬁltrate was treated with Mayer’s reagent (3 drops), whereas
another portion was similarly treated with Dragedorff’s re-
agent. Turbidity or precipitation with these reagents was
considered as evidence for the presence of alkaloids.
Test for ﬂavonoids. Two milliliters of the aqueous ex-
tract was heated, and a piece of metallic magnesium fol-
lowed by concentrated hydrochloric acid (5 drops) was
added. A red or orange coloration indicated the presence of
Adult albino rats of either sex weighing 160–210 g were
fed a standard pellet diet and water ad libitum. Food, but not
water, was withdrawn 18 hours before the experiments.
Wistar rats were divided into ﬁve groups, each com-
posed of six rats. Rats in the ﬁrst three groups received
aqueous extract of L. nobilis leaf at 3 mL/kg (100, 200,
and 400 mg/kg, respectively); the doses were given intra-
peritoneally, and the largest safe dose was used as deter-
mined by preliminary 50% lethal dose experiments. The
fourth group received the antidiarrheatic agent diphenox-
ylate at 3 mL/kg of 5 mg/kg solution as a positive control,
and the ﬁfth group received 3 mL/kg PSS and served as a
negative control. Rats were then housed singly in cages
lined with white blotting paper. One hour after the treat-
ments, each rat was given 1 mL of castor oil orally. Rats
were observed for the presence of diarrhea on an hourly
basis for the next 5 hours after the castor oil administra-
tion. For the purpose of this study, diarrhea was considered
as defecation of watery, unformed stool. The number of
wet droppings was counted every hour for a period of 5
hours. The total of the wet droppings after 5 hours was
counted and averaged.
Intraluminal ﬂuid accumulation was determined by the
method of Robert et al.
Fasting rats were divided into four
groups of six animals each. Group 1 received 3 mL of PSS/
kg intraperitoneally and served as the control. Groups 2, 3,
and 4 were injected intraperitoneally with the plant extract at
100, 200, or 400 mg/kg, respectively, in a total volume of
3 mL/kg. The above treatments were given 1 hour before the
administration of 1 mL of castor oil orally. Two hours later
the rats were sacriﬁced, and the small intestine was ligated at
both pyloric sphincter and ileocecal junction, dissected out,
and weighed. The intestine was reweighed after milking off
the contents, and the difference between the weights of
loaded and empty intestines was calculated as the weight of
The effect of aqueous extract of L. nobilis on gastroin-
testinal transit was tested using the charcoal meal method.
One-half milliliter of charcoal meal (5 g of activated char-
coal suspended in 50 mL of PSS) was given to ﬁve groups of
six rats each. In the ﬁrst three groups, the charcoal meal was
administered to animals intragastrically 60 minutes after the
intraperitoneal injection of aqueous extract of L. nobilis leaf
52 QNAIS ET AL.
at 3 mL/kg of 100, 200 and 400 mg/kg, respectively. In the
fourth group, which served as a positive control, rats were
treated with atropine sulfate at 3 mL/kg of 1 mg/kg. The ﬁfth
group (control) was treated with 3 mL/kg PSS before re-
ceiving the charcoal meal.
Animals were killed 60 minutes after charcoal adminis-
tration, and the small intestine, from the pylorus to the ce-
cum, was rapidly removed and laid out on white ﬁlter paper
for inspection. The distance traveled by the front of the
charcoal meal was measured and calculated as a percentage
of the total length of the intestine.
Rats were lightly anesthetized with ether and were sac-
riﬁced by a sharp blow to the head, and the abdomen
was opened. Segments of the ileum (1–2 cm long) were
removed and dissected free of adhering mesentery. The
lumen was ﬂushed with PSS to remove any remaining
contents. PSS was prepared daily and had the following
composition: 118 mMNaCl, 4.7 mMKCl, 2.5 mM
O, 1.0 mMMgCl
O, 0.5 mMNaH
, and 11.1 mMglucose. The preparations
were mounted under a tension of 1 g in a 10-mL organ bath
containing PSS at 37 –1C and aerated with a gas mixture
and 5% CO
). The responses were recorded iso-
metrically on a minigraph (Lafayette Instrument Co., La-
fayette, IN, USA). After a 60-minute equilibration period
during which the PSS was replaced every 15 minutes,
concentration–effect curves for the aqueous extract of
L. nobilis leaf (1, 50, 100, 225, 316, and 400 mg/mL) were
established. The responses of the ileum to the aqueous
extract of L. nobilis leaves were expressed as percentages
of the maximum relaxation to a nonspeciﬁc relaxant agent
M), which was added at the end of the
Data were expressed as mean –SEM values. Statistical
signiﬁcance was assessed by Student’s ttest, and differences
were considered signiﬁcant when P<.05. Experimental data
were analyzed by a computer-ﬁtting treatment using
GraphPad Prism version 5.0 software (GraphPad Software,
San Diego, CA, USA). The effective concentration pro-
ducing 50% of the maximum response (EC
) was calcu-
lated by the best visual ﬁt from the plot of the individual
Effect of L. nobilis aqueous extract on castor
One hour after administration of castor oil, diarrhea was
apparent in the control group, and it persisted for the next 4
hours (Table 1). This was largely eliminated by the intra-
peritoneal injection of diphenoxylate in the fourth group.
L. nobilis aqueous extract signiﬁcantly inhibited the diar-
rheal effect of castor oil in a dose-dependent manner. The
was 150 –6.4 mg/kg.
Effect of L. nobilis aqueous extract on castor
L. nobilis extract (100, 200, and 400 mg/kg) caused a
signiﬁcant dose-dependent decrease in castor oil-induced
enteropooling in rats (Table 2), with an EC
of 162 –
Effect of L. nobilis aqueous extract
on small intestinal transit
The aqueous extract of L. nobilis (100, 200, and 400 mg/kg)
caused a dose-dependent decrease in the propulsion of
the charcoal meal through the gastrointestinal tract com-
pared with the control group (Table 3). The EC
139 –3.1 mg/kg. The inhibition of intestinal transit pro-
duced by the extract was not as prominent as that caused by
Table 1. Effect of L. nobilis Aqueous Extract on Diarrhea
Induced by 1mL of Castor Oil in Rats
Mean of wet/loose
feces in 5 hours % inhibition
PSS 3 mL/kg 17.0 –2.1 —
L. nobilis 100 mg/kg 14.2 –2.4 16
L. nobilis 200 mg/kg 10.5 –2.1** 38
L. nobilis 400 mg/kg 6.7 –1.2** 61
Diphenoxylate 5 mg/kg 4.0 –0.7** 76
Rats were treated with different concentrations of aqueous extract of L.
nobilis leaf, the antidiarrheatic agent diphenoxylate, or physiological salt
solution (PSS). Castor oil was given orally to all animals 1 hour after
treatment, and the number of wet droppings was counted every hour for 5
hours. The mean –SEM value (n=6) of the wet/loose feces was calculated and
averaged for the 5-hour period.
**P<.05, signiﬁcantly different from control by Student’s ttest.
Table 2. Effect of L. nobilis Aqueous Extract
on Enteropooling Induced by 1mL of Castor Oil in Rats
PSS 3 mL/kg 7.35 –0.21 1.80 –0.40 —
L. nobilis 100 mg/kg 7.72 –0.37 1.60 –0.21 11
L. nobilis 200 mg/kg 8.01 –0.52 1.18 –0.29** 34
L. nobilis 400 mg/kg 7.26 –0.44 0.81 –0.12** 55
Rats were treated either with different concentrations of aqueous extract of
L. nobilis leaf or with PSS. Castor oil was given orally to all animals 1 hour
after treatment. Two hours later, rats were sacriﬁced, and small intestine was
ligated, dissected out, and weighed. The intestine was reweighed after milking
off the contents, the difference was calculated and averaged, and the
percentage of inhibition of enteropooling relative to the PSS control was
calculated. Data are mean –SEM values (n=6).
**P<.05, signiﬁcantly different from control by Student’s ttest.
L. NOBILIS LEAF EXTRACT EFFECT ON DIARRHEA 53
Effect of L. nobilis aqueous extract
on the tone of isolated ileum
The aqueous extract (50–400 mg/mL) caused a concen-
tration-dependent decrease in the amplitude of the phasic
contractions and relaxed the tone of the longitudinal seg-
ments of the ileum (Fig. 1). The EC
of aqueous extract for
relaxation of ileal segments was 71 –5.3 mg/mL (n=6). The
relaxant effect of aqueous extract was fully reversible after
washout of the extract and replacement with PSS.
The castor oil test has been extensively used in pharma-
cology to induce diarrhea and to evaluate antidiarrheal
properties of potential drugs in rats, and castor oil–induced
diarrhea in rats has been used to reproduce certain aspects of
The diarrheal effect of castor oil has
been attributed to several possible mechanisms. On the one
hand, castor oil liberates the active principle, ricinoleic acid,
which results in irritation and inﬂammation of the intestinal
mucosa. This leads to the release of prostaglandins and
perhaps other autacoids,
which stimulate motility and se-
cretion, two strongly suspected factors that may cause di-
arrhea. On the other hand, castor oil and its active principle
reduce active Na
absorption and decrease Na
-ATPase activity in the small intestine and colon.
will lead to decreased absorption, another factor that pre-
disposes to diarrhea. Moreover, nitric oxide has been shown
to mediate, in part, the laxative effects of castor oil, although
it offers a protective effect against mucosal damage caused
by the laxative.
Other effects have also been reported.
The present experiments demonstrate that the aqueous
leaf extract of L. nobilis has an antidiarrheal effect. This has
been demonstrated by the following observations: (1) the
dose-dependent decrease in the number of wet/loose feces
during a period of 5 hours after castor oil administration; (2)
the signiﬁcant reduction of enteropooling; and (3) the sig-
niﬁcant reduction of charcoal transit in animals treated with
the aqueous extract, because decreasing the intestinal mo-
tility is considered one of the goals of the antidiarrheal
Many antidiarrheal agents, among them codeine
and octreotide, have an antimotility effect.
opiods, which are effective antidiarrheal agents, also block
intestinal propulsion. Presumably, these substances increase
the contact time of materials with the intestinal mucosa, an
effect that is assumed to enhance the likelihood of absorp-
In addition, (4) concentration-dependent relaxation
of small intestine is caused by the leaf extract because it has
been shown that spasmolytic agents are effective antidiar-
In support of this, the observed antidiarrheal
effect of wood creosote has been partly attributed to inhi-
bition of the amplitude of the spontaneous phasic contrac-
tions of longitudinal and circular smooth muscles in guinea
pig intestinal segments, as well as contractions induced by
Of particular interest is the inhibition of enteropooling by
the leaf extract of L. nobilis. Enteropooling caused by castor
oil may result from secretory diarrhea, which results in ac-
cumulation of water and electrolytes in the intestinal lumen.
Table 3. Effect of L. nobilis Aqueous Extract on Intestinal
Motility 60 Minutes After Charcoal Administration
of charcoal meal (%) % inhibition
PSS 3 mL/kg 65.6 –3.1 —
L. nobilis 100 mg/kg 59.1 –1.9 10
L. nobilis 200 mg/kg 48.5 –2.3** 26
L. nobilis 400 mg/kg 39.5 –4.1** 40
Atropine 1 mg/kg 31.2 –4.1** 52
Rats were treated with different concentrations of aqueous extract of L.
nobilis leaf, the anticholinergic agent atropine sulfate, or PSS. One-half
milliliter of charcoal meal was given to all animals 1 hour after treatment. One
hour later, the small intestine was removed, and the distance traveled by the
charcoal was measured, calculated as a percentage of intestine length, and
averaged for every group. Data are mean –SEM values from six animals.
**P<.05, signiﬁcantly different from control by Student’s ttest.
FIG. 1. (A) Effect of increasing concentrations of aqueous extract
(AE) of L. nobilis leaf on rat isolated ileum. Segments of the ileum
were isolated and mounted for isometric recording. The effect of
washing out AE is shown. pap, papaverine. (B) Concentration–effect
curve for increasing concentrations of the AE of L. nobilis leaf on rat
isolated ileum. Data are mean –SEM values of six experiments.
54 QNAIS ET AL.
Some diarrhea-causing agents, like cholera toxin, activate
adenylate cyclase in the enterocytes and increase the pro-
duction of cyclic AMP, which inhibits Na
secretion, thus leading to massive water se-
cretion into the lumen and to secretory diarrhea.
secretory diarrhea toxins such as Escherichia coli heat-sta-
ble enterotoxin may activate a similar mechanism except
that the second messenger is cyclic GMP.
Castor oil and its metabolite ricinoleic acid are among the
list of drugs associated with secretory diarrhea, functioning
probably through stimulation of cyclic AMP production.
The signal transduction of this second messenger involves
phosphorylation of membrane proteins that are involved in
ion transport, resulting in active secretion of Cl
efﬂux of Na
, and water, leading to net ﬂuid secretion.
Furthermore, castor oil has been shown to inhibit intestinal
-ATPase activity, thus reducing normal ﬂuid ab-
The pump that is located in the basolateral
membranes of enterocytes creates electronegativity inside
the cell, which serves, in part, as a driving force for sodium
and water entry from the intestinal lumen into the cell. Once
a cell is inhibited by castor oil or its metabolite, Na
water absorption would be compromised, and enteropooling
would occur. The observation that the leaf extract of L. nobilis
inhibited enteropooling (EC
=162 –5.9 mg/kg) suggests
that either absorption was enhanced or secretion was in-
hibited, or both processes occurred. Whether this effect re-
sults from inhibition of cyclic AMP production, stimulation
-ATPase, or some other mechanism cannot be
resolved from the present experiments.
Many components in the leaf extract could have been
responsible for the observed effect. Phytochemical analysis
of the aqueous extract of L. nobilis in our laboratory re-
vealed the presence of ﬂavonoids, alkaloids, and tannates.
Each of these constituents is a potential candidate to mediate
the antidiarrheal properties of L. nobilis extract. For exam-
ple, tannic acid and tannins are water-soluble polyphenols
that are present in many plants and to which the antidiar-
rheal effect of many plants have been attributed.
been argued that the presence of tannates in the aqueous
extract of L. nobilis leaf may make the intestinal mucosa
more resistant to secretion and thereby reduces secretion.
On the other hand, ﬂavonoids have antidiarrheal proper-
ties, and this activity has been attributed to their ability to
inhibit intestinal mobility and hydroelectrolytic secretion.
Furthermore, ﬂavonoids, such as quercetin, inhibit the in-
testinal secretory response to prostaglandin E
both in vitro
and in vivo,
despite observations to the contrary that
showed that dietary quercetin induces Cl
secretion in rat
small and large intestine.
Also, ﬂavonoids and alkaloids are
known to inhibit the release of autacoids and prostaglan-
This effect is interesting because prostaglandins, in
particular prostaglandin E
, are known to induce a secretory
response in the intestine
and to stimulate motility.
To stress the potential role of ﬂavonoids in the present
observations, phytochemical investigation of L. nobilis
leaves and fruits led to the isolation of the ﬂavonoids api-
genin, luteolin, kaempferol, myrecitin, and quercitin as well
as sesquiterpene lactones, alkaloids, monoterpenes, germa-
crane alcohols, and glycosylated ﬂavones.
The total con-
tent of ﬂavonoids was 0.68 mg/g of leaves. This observation
is of particular interest because ﬂavones typically have an
inhibitory effect on Cl
channels when present in relatively
high concentrations. In particular, luteolin and quercitin
both were found in the aqueous extract of L. nobilis leaf
and showed potent inhibitory effect on Cl
the membrane of a human colonic epithelial cell line.
aqueous extract in our experiments contains such ﬂavo-
noids, then it is likely that they inhibit Cl
the cystic ﬁbrosis transmembrane conductance regulator
channel, which is the major Cl
channel in the intestinal
epithelium. This would explain the inhibition of en-
teropooling observed in the present experiments and would
explain in part the mechanism of action of L. nobilis leaf
extract. In addition, we have demonstrated a direct inhibi-
tory effect of the aqueous leaf extract on intestinal smooth
muscle motility, an effect that has been induced consistently
Other indirect effects such as inhibition of
the release of autacoids need to be investigated.
The inhibitory effect of the aqueous extract of L. nobilis
leaf justiﬁes the use of the plant in folk medicine as a
nonspeciﬁc antidiarrheal agent. The extract meets some of
the criteria for acceptance as an antidiarrheal agent.
criteria include inhibition of the production of wet or un-
formed feces in animals, as demonstrated in our experi-
ments, and the inhibition of gastrointestinal propulsive
action, which was demonstrated using the charcoal meal
transit. Also, because decreasing the intestinal motility is
one of the goals of the antidiarrheal therapy,
the use of the
aqueous extract of L. nobilis leaf seems to be consistent with
In conclusion, the present experiments show that the
aqueous extract of L. nobilis leaf has an antidiarrheal effect
as demonstrated by a decrease in the number of wet/loose
feces, enteropooling, and intestinal charcoal meal transit and
by inhibition of ileal smooth muscle tone. The experiments
support the traditional medicine use of the aqueous leaf
extract of the plant in the treatment of diarrhea. The active
constituents responsible for the antidiarrheal activity remain
to be identiﬁed, although ﬂavonoids, alkaloids, and tannates
are likely candidates. Further studies are needed to under-
stand the mechanism of this observed antidiarrheal action.
This study was supported by a grant of the Deanship for
Scientiﬁc Research, Hashemite University.
AUTHOR DISCLOSURE STATEMENT
No competing ﬁnancial interests exist.
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L. NOBILIS LEAF EXTRACT EFFECT ON DIARRHEA 57