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Journal of Natural Pharmaceuticals, Volume 2, Issue 3, July-September, 2011
158
Address for
correspondence:
AOT Ashafa,
Department of Plant
Sciences, University of
the Free State, Qwaqwa
Campus, Phuthaditjhaba,
South Africa. E-mail: tom.
ashafa@gmail.com
Department of Plant Sciences,
University of the Free
State, Qwaqwa Campus,
Phuthaditjhaba, South Africa,
1
Department of Biochemistry,
University of Ilorin, Ilorin,
2
Department of Botany, Lagos
State University, Ojo Campus,
Lagos, Nigeria
Laxative potential of the ethanolic leaf extract of Aloe vera (L.)
Burm. f. in Wistar rats with loperamide-induced constipation
A. O. T. Ashafa, T. O. Sunmonu
1
, A. A. Abass
2
, A. A. Ogbe
2
ABSTRACT
Background: Constipation is a highly prevalent and often chronic functional gastrointestinal disorder
affecting humans irrespective of race and color exposing victims to colorectal cancer. The present study
evaluated the effi cacy of the ethanolic leaf extract of Aloe vera against loperamide-induced constipation in
rats. Materials and Methods: Rats were constipation induced by the oral administration of loperamide (3
mg/kg body weight) while the control animals received normal saline. Constipated rats were treated with
50, 100, and 200 mg/kg body weight/day of the ethanolic leaf extract for 7 days during which the feeding
characteristics, body weight, fecal properties, and gastrointestinal transit ratio were monitored. Results:
Treatment of constipated rats with the extract at 50, 100, and 200 mg/kg body weight for 7 days improved
intestinal motility, increased fecal volume, and normalized body weight in the constipated rats. These are
indications of the laxative property of the herb with the 200 mg/kg body weight of the extract showing the
best effi cacy. Conclusion: The effect of the extract compares favorably well with Gaviscon, a standard
laxative drug. These fi ndings have therefore lent scientifi c support to the use of the herb as a laxative agent
in Nigerian folkloric medicine.
Key words: Aloe vera, constipation, ethanolic extract, folk medicine, Gaviscon, intestinal motility
INTRODUCTION
Constipation is a highly prevalent and
often chronic functional gastrointestinal
disorder affecting 3-15% of the general
population.
[1-4]
It is a common clinical problem
comprising a constellation of symptoms that
include excessive straining, hard stools,
feeling of incomplete evacuation, use of
digital maneuvers, or infrequent defecation.
A number of conditions such as metabolic
problems, fiber deficiency, anorectal
problems, and drugs can cause constipation.
Functional constipation consists of two
subtypes, namely, slow-transit constipation
and dyssynergic defecation. Some patients
with irritable bowel syndrome may exhibit
features of both types of constipation.
[5]
Laxatives are agents that add bulk to
intestinal contents by retaining water
within the bowel lumen by virtue of their
osmotic effects, or that stimulate intestinal
secretion or motility thereby increasing
the frequency and ease of defecation.
[6,7]
The use of chemical drugs such as Senna,
Correctol, Exlax, Senokot, and Gaviscon
(containing sennosides as active ingredients)
for the treatment of constipation is common
among affected individuals. However, the
use of these orthodox drugs is limited
due to their high cost, undesirable side
effects (such as stomach pain and cramps),
and slow activity (up to 8 h) in relieving
constipation.
[3,4,8]
Therefore, almost half of
patients with constipation are not satisfi ed
with the effi cacy of orthodox laxatives in
improving quality of life.
[9,10]
Consequently,
attention has been shifted to the use of
medicinal plants for the treatment of the
menace particularly in Nigeria.
[11,12]
There
is the general belief among users that plant
extracts are cheap, fast acting, and readily
available coupled with the availability of
several choices.
[13]
Therefore, the continuous
search for a more natural, effective,
affordable and readily available laxative of
plant origin necessitated this research.
From time immemorial, aloe plants have
been used medicinally for centuries for
the treatment of diverse disorders and
Original Article
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Website: www.jnatpharm.org
DOI:
DOI: 10.4103/2229-5119.86268
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Journal of Natural Pharmaceuticals, Volume 2, Issue 3, July-September, 2011
159
ailments such as diabetes and ulcer.
[14]
There are at
least four species of the over 360 known ones that have
medicinal properties – Aloe arborescens Miller; Aloe
perryi Baker; Aloe ferox Miller, and Aloe barbadensis
Miller, also known as Aloe vera.
[14,15]
Among them, A. vera
is the most widely used healing plants in the history of
mankind.
[16]
Aloe vera (L.) Burm. f. is perennial, succulent
xerophytes which develops water storage tissues in
the leaves to survive in dry areas of low or erratic
rainfall. The innermost part of the leaf is a clear, soft,
moist, and slippery tissue that consists of large, thin-
walled parenchyma cells in which water is held in the
uniform of viscous mucilage.
[17,18]
A. vera has been part
of the traditional medicine practices of many regions of
the world for centuries and the medicinal effi cacy has
been attributed to the aggregation of over 75 bioactive
phytochemicals.
[19]
These comprise basically
polysaccharides and anthraquinones which are
concentrated in the inner leaf parenchymatous tissues
of the plant.
[20,21]
The medicinal activities of the plant have
been reported to be as a result of synergistic action of the
compounds (such as cellulose and aloe-emodin) contained
therein rather than a single chemical substance.
[22]
The
bioeffi cacy reports of A. vera include antimicrobial,
[21,23]
antiviral,
[24]
antioxidant,
[25]
anti-psoriasis,
[26]
antidiabetic,
[27-30]
cardiac stimulatory,
[31]
antiulcer,
[32]
immunomodulatory,
[33,34]
anti-inflammatory,
[35,36]
anticancer,
[37]
and hepatoprotective properties.
[38]
Although the traditional use of A. vera as a laxative is
known but little or no scientifi c credence is available in
the literature on the purgative potential of this plant.
The present study therefore investigated the laxative/
purgative activity of A. vera in loperamide-induced
constipated experimental animals and the effect was
compared with Gaviscon, a standard laxative drug. The
result from this study is expected to shed more light on
the minimum required dosage of the A. vera crude extract
that will provide an effective laxative activity.
MATERIALS AND METHODS
Drugs and chemicals
Loperamide hydrochloride, carmine, and
carboxymethylcellulose were procured from Sigma
Chemical Co. (St. Louis, MO, USA) while Gaviscon was
a product of Reckitt Benckiser Pharmaceutical (Pty) Ltd.
(Elandsfontein, South Africa). All other chemicals and
reagents used were of analytical grade.
Plant materials
Fresh, mature leaves of A. vera were collected from the
Ojo area of Lagos State, Nigeria, from homes where the
plant is grown in pots. The plant was authenticated by
Mr. OK Oluwa, a biosystemanist in the Department of
Botany, Lagos State University, and a voucher specimen
(AshMed. 2010/LHB01) was prepared and deposited in
the university herbarium.
Preparation of the ethanolic extract
The leaves of A. vera were thoroughly washed with
distilled water, cut into thin slices, and air-dried at
room temperature to a constant weight. The dried leaves
were grinded into a powder and 40 g of the material was
extracted by shaking it for 24 h in 500 ml of ethanol. The
extract obtained was fi ltered through Whatman no. 1
(70 mm) fi lter paper and concentrated on a water bath
at 45°C to give a yield of 5.2 g. This was reconstituted in
distilled water to give the required doses of 50, 100, and
200 mg/kg body weight for the experiment.
Animal used
Male albino rats (Rattus norvegicus) of the Wistar strain
with a mean weight of 150 ± 4.22 g were bred in the
animal house of the Department of Biochemistry, Lagos
State University. The animals were housed individually
in clean metabolic cages placed in a well-ventilated
house under optimum conditions (temperature 23 ± 1°C;
photoperiod: 12 h natural light and 12 h dark; humidity:
45–50%). They were acclimatized for 7 days after being
selected for the experiment, during which they were
allowed free access to commercial pelleted rat chow
(Lagos State Agro-Products, Agric Farm, Ojo, Lagos) and
water ad libitum. The cleaning of the cages was done on
a daily basis. All animal treatments were in accordance
with international ethical guidelines and the National
Institute of Health Guide concerning the care and use of
laboratory animals. The study was carried out following
the approval from the Ethical Committee of the Lagos
State University on the use and care of animals.
Induction of constipation in the rats
Constipation was induced in the animals by the oral
administration of 1 ml loperamide (3 mg/kg body weight
in 0.9% sodium chloride for 3 days),
[39]
while the control
rats were administered with the normal saline only. The
passage of reduced, hard, and dry fecal pellets indicated
constipation in the rats.
Experimental design
A total of 36 Wistar rats were used for the experiment
and they were grouped into 6 with each group comprising
6 animals each. Those in Groups 1 (control) and 2
(constipated control) were administered with distilled
water. Groups 3, 4, and 5 comprised constipated rats given
50, 100, and 200 mg/kg body weight/day of the A. vera
ethanolic extract, respectively, while Group 6 consisted
of constipated rats administered with Gaviscon. The
administration was done using a metal oropharyngeal
cannula. The water intake, feed intake, and body weight
gain of all the rats were recorded during the experimental
period and treatment lasted for 7 days.
Ashafa, et al.: Laxative effect of A. vera in Wistar rats
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Journal of Natural Pharmaceuticals, Volume 2, Issue 3, July-September, 2011
160
Figure 1: Eff ect of the ethanolic extract of A. vera on the GIT ra o in rats
with loperamide-induced cons pa on
Total number, dry weight, and water content of
the fecal pellet
The excreted fecal pellets of individual rats were
collected daily at 09:00 am throughout the duration of
the experiment. The total number, weight, and water
content of the pellets were determined. The water content
was calculated as the difference between the wet and dry
weights of the pellet.
Gastrointestinal transit ratio
The gastrointestinal (GIT) ratio was measured
according to the method of Nagakura et al.
[40]
On the
day 7, 1 ml of carmine (3 g suspended in 50 ml of 0.5%
carboxymethylcellulose) was orally administered to
the rats. One hour after the marker was administered,
the animals were humanely sacrifi ced and the small
intestines were quickly removed. The distance over which
the carmine had traveled and the total length of the small
intestine were measured. The GIT ratio was expressed as
the percentage of the distance travelled by the carmine
relative to the total length of the small intestine.
Statistical analysis
Data were expressed as means ± SD of six replicates and
were subjected to one-way analysis of variance (ANOVA)
followed by the Duncan multiple range test to determine
signifi cant differences in all the parameters. Values were
considered statistically signifi cant at P < 0.05.
RESULTS
The administration of loperamide signifi cantly reduced
the water intake, the number, water content, and the
weight of the fecal pellets [Table 1]. This indicated that
constipation had been induced in the rats. However, no
signifi cant difference was observed in the feed intake
between the control and the constipated animals.
While water consumption decreased in the untreated
constipated rats, the administration of the ethanolic
extract of A. vera significantly increased the water
intake in constipated rats [Table 2]. Again, there was
no signifi cant difference in the feed intake of all the
animals. Similarly, the extract signifi cantly increased
the number, water content, and weight of fecal pellets
in the constipated rats in a dosage-dependent manner.
The body weights of the constipated animals were also
normalized following the treatment with the extract.
Loperamide signifi cantly reduced the gastrointestinal
motility in the untreated constipated rats [Figure 1].
Treatment with the A. vera extract, however, increased
the gastrointestinal movement in a dose-dependent
manner which compared favorably well with Gaviscon,
a standard laxative drug.
DISCUSSION
Plants have long been a very important source of drugs
against several diseases including constipation. In Nigeria,
a reasonable percentage of the population depends on
herbal medicines because the international commercial
medicines are becoming increasingly expensive and out
Ashafa, et al.: Laxative effect of A. vera in Wistar rats
Table 1: Eff ect of the loperamide administra on on feed intake, water
intake, and fecal proper es of cons pated rats
Parameters Normal control Cons pated rats
Feed intake 16.85 ± 1.21 18.76 ± 0.98
*
Water intake 20.90 ±1.34 9.81 ± 0.85
**
Number of fecal pellets 71.14 ± 3.82 26.44 ± 1.03
**
Water content of fecal pellets 1.67 ± 0.18 0.63 ± 0.12
**
Weight of fecal pellets 7.02 ± 0.53 3.25 ± 0.10
**
Data are mean ± SD values (n = 6).
*
Not signifi cantly diff erent from normal controls
(P < 0.05).
**
Signifi cantly diff erent from normal controls (P < 0.05).
Table 2: Eff ect of the ethanolic leaf extract of A. vera on feed and water intake, body weight gain, and fecal proper es of cons pated rats
Parameters Cons pated + A. vera (mg/kg body weight)
Normal control Cons pated control 50 100 200 Gaviscon
Feed intake 25.29 ± 1.62
a
24.66 ± 1.40
a
23.21 ± 1.19
a
22.94 ± 1.18
a
23.30 ± 1.23
a
23.12 ± 1.25
a
Water intake 53.80 ± 2.59
a
42.80 ± 2.86
b
51.00 ± 2.85
a
53.78 ± 2.82
a
54.08 ± 2.56
a
53.40 ± 2.93
a
Number of fecal pellets 77.80 ± 2.59
a
36.80 ± 4.94
b
50.40 ± 3.25
c
62.20 ± 3.68
d
74.20 ± 3.75
a
78.00 ± 3.54
a
Water content of fecal pellets (ml) 1.87 ± 0.08
a
1.33 ± 0.04
b
1.43 ± 0.07
c
1.55 ± 0.06
c
2.14 ± 0.06
d
2.08 ± 0.07
d
Weight of fecal pellets (g) 8.77 ± 0.61
a
3.93 ± 0.27
b
6.26 ± 0.26
c
8.52 ± 0.36
a
8.84 ± 0.32
a
9.01 ± 0.25
a
Body weight gain (g) 13.20 ± 0.96
a
31.78 ± 1.00
b
12.17 ± 0.91
a
11.12 ± 1.69
a
10.48 ± 1.55
a
13.22 ± 1.11
a
Data are mean ± SD values (n = 6). Row values with superscripts diff erent from the control are signifi cantly diff erent (P < 0.05).
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Journal of Natural Pharmaceuticals, Volume 2, Issue 3, July-September, 2011
161
of reach coupled with the undesirable side effects.
[11,12]
The present study has clearly demonstrated that the
aqueous extract of A. vera has a laxative activity, which
is comparable to Gaviscon.
The use of loperamide as a constipation inducer is well
documented. The drug is an opioid agonist antidiarrheal
that inhibits intestinal water secretion and colonic
peristalsis.
[41,42]
This inhibition extends fecal evacuation
time and delays intestinal luminal transit.
[43]
Loperamide-
induced constipation is therefore considered to be a model
of spastic constipation.
[44]
The observed reduction in the number, weight, and water
content of fecal pellets following the treatment with the
drug indicated induction of constipation in the rats.
A similar observation was reported by Shimotoyodome
et al.
[45]
and Wintola et al.
[3]
The reduction in the water
consumed by the constipated animals may also be due
to the effect of the drug which probably accounted for
the reduction in the water content of the fecal pellets.
However, the drug did not prevent the animals from
feeding adequately.
The administration of the ethanolic leaf extract of
A. vera to the constipated rats was effective in infl uencing
the increased defecation frequency, fecal volume, and
motility of the colon. These are indications of the laxative
property of the plant extract. This may be due to the
presence of anthranoid glycosides derivatives of which
aloin is the main compound.
[46]
According to Izzo et al.,
[47]
aloin is metabolized by the colonic fl ora to reactive aloe-
emodin which is responsible for the purgative activity
of this plant. This compound possibly exerts its action
by disturbing the equilibrium between the absorption
of water from the intestinal lumen via an active sodium
transport
[48]
and the secretion of water into the lumen by
a prostaglandin-dependent mechanism.
[49]
Although the feed intake did not differ among the groups,
the gain in body weight was higher in the untreated
constipated rats compared to the extract-treated groups.
This may be due to the accumulation of fecal pellets
in their bodies, thus accounting for the extra weight.
This clearly indicates that the plant extract increased
intestinal secretion and motility in the constipated
rats. A similar observation was reported by Niwa
et al.
[50]
where dietary fi ber was used for the treatment
of morphine-induced constipation in rats. Wintola et al.
[3]
also recorded a similar observation during the treatment
of constipated rats with A. ferox. Of particular interest
is the fact that the effect of the A. vera extract was dose
dependent in this study. The effect of the highest dosage
actually compared favorably well with Gaviscon.
The transit process of the entire gastrointestinal tract
refl ected the overall gastrointestinal motor activity.
Measuring the colonic transit time is useful in constipation,
abdominal bloating, and refractory irritable bowel
syndrome.
[3]
It also provides quantitative information
about the colonic transit, enables the identifi cation and
characterization of transit abnormalities, and allows the
assessment of the severity of the problem as well as the
response to therapy.
[51]
In this study, carmine was used
as the marker to measure the colonic movement. The
A. vera ethanolic extract increased the intestinal motility
which, in turn, enhanced colonic peristalsis in the rats.
The possible mechanism of the extract in this process
may be enhancing the release of fl uid thereby increasing
intestinal secretion. The laxative effect of the extract
could also be attributed to changes in the intestinal
motility, which produced an increase in the intestinal
transit and colonic movement.
[52]
Generally, the effect of
the treatment with the extract compared favorably well
with Gaviscon. The present study compares favorably
well with that of Wintola et al.
[3]
where an A. ferox extract
was used. This is an indication that the herb was effective
in ameliorating bowel obstruction, thereby enhancing
easy movement in the intestine.
CONCLUSION
The present study revealed that oral administration
of the ethanolic extract of A. vera exhibited a laxative
activity in rats with loperamide-induced constipation
rats. This suggests the benefi cial effects of the herb
in improving intestinal motility. Noteworthy is the
fact that the extract at the highest dose of 200 mg/kg
body weight showed the best laxative action, which
compared favorably with Gaviscon. These fi ndings have
lent scientifi c support to the use of A. vera as a laxative
agent in Nigerian folkloric medicine.
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Ashafa, et al.: Laxative effect of A. vera in Wistar rats
Cite this article as: Ashafa AO, Sunmonu TO, Abass AA, Ogbe AA. Laxative
potential of the ethanolic leaf extract of Aloe vera (L.) Burm. f. in Wistar rats
with loperamide-induced constipation. J Nat Pharm 2011;2:158-62.
Source of Support: Nil. Confl ict of Interest: None declared.
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