Anti-ulcer effect of Aloe vera in non-steroidal anti- inflammatory drug induced peptic ulcers in rats

Abstract

This study was performed to determine the effects of Aloe vera on indomethacin induced ulcers in rats. Albino rats (Wister strain) of either sex weighing between 150 and 200 gms were randomly allotted into four groups with six animals each. Indomethacin was administered orally in the dose of 20 mg/kg body weight and kept fasting for 6 h. A. vera powder was mixed with gum acacia, the solution was administered orally through the oral gavage to rats in the dose of 200 mg/kg. Omeprazole (20 mg/kg) was administered intraperitoneally as a standard drug for present study. At the end of the study, rats were sacrificed and stomachs were opened and stored in 5% formalin solution, ulcer index and histological changes were studied. Student-'t' test analysis was used for the present study. It was found that A. vera showed statistically significant anti-ulcer activity comparable to standard drug omeprazole. The mean ulcer indexes of two drugs were statistically significant (P value is < 0.001). Therefore, the results were suggestive of anti ulcerogenic activity of A. vera.

Full text

African Journal of Pharmacy and Pharmacology Vol. 5(16), pp. 1867-1871, 29 October, 2011
Available online at http://www.academicjournals.org/AJPP
DOI: 10.5897/AJPP11.306
ISSN 1996-0816 © 2011 Academic Journals
Full Length Research Paper
Anti-ulcer effect of Aloe vera in non-steroidal anti-
inflammatory drug induced peptic ulcers in rats
Sai Krishna Borra*, Radha Krishna Lagisetty and Gowrinath Reddy Mallela
Department of Pharmacology, Kamineni Institute of Medical Sciences, Narketpally, Nalgonda District, Andhra Pradesh,
India.
Accepted 1 September, 2011
This study was performed to determine the effects of Aloe vera on indomethacin induced ulcers in
rats. Albino rats (Wister strain) of either sex weighing between 150 and 200 gms were randomly
allotted into four groups with six animals each. Indomethacin was administered orally in the dose of 20
mg/kg body weight and kept fasting for 6 h. A. vera powder was mixed with gum acacia, the solution
was administered orally through the oral gavage to rats in the dose of 200 mg/kg. Omeprazole (20
mg/kg) was administered intraperitoneally as a standard drug for present study. At the end of the
study, rats were sacrificed and stomachs were opened and stored in 5% formalin solution, ulcer index
and histological changes were studied. Student-‘t’ test analysis was used for the present study. It was
found that A. vera showed statistically significant anti-ulcer activity comparable to standard drug
omeprazole. The mean ulcer indexes of two drugs were statistically significant (P value is < 0.001).
Therefore, the results were suggestive of anti ulcerogenic activity of A. vera.
Key words: Aloe vera, gastric ulcer, indomethacin, omeprazole.
INTRODUCTION
Peptic ulcer is a chronic disease which impairs the quality
of life and is associated with increased morbidity and
mortality. Peptic ulcer disease is a worldwide problem.
Statistics from all sources indicate 10% or more of adult
population are affected within their life time and 50% of
healthy individuals complain of dyspepsia (Laurence,
1996). Peptic ulcer affects individuals from 20 to 60 years
of age with males being predominantly affected. The
incidence of duodenal ulcer is more frequent than gastric
ulcer (ratio 4:1). Considering the etiology of peptic ulcers,
there are two prime factors responsible: the “aggressive”
factors and the “defensive” factors. Ulcers are caused by
and they persist as a result of imbalance between
aggressive and defensive factors. The aggressive factors
include acid, pepsin, free radicals, infectious agents as
Helicobacter pylori, chemicals and to a lesser extent bile
salts and pancreatic enzymes. While the defensive
factors include the adherent mucin, bicarbonate,
prostaglandins and mucosa blood flow. Due
*Corresponding author. E-mail: saikrishnaborra@gmail.com.
Tel: +91 7299131473.
to any cause, an increase in aggressive factors or a
decrease in defensive factors will lead to loss of mucosal
integrity resulting in ulceration (Alan, 1985). Etiological
factors include: diet (Lewis, 1978), tobacco smoking
(Doll, 1958), alcohol consumption (Hagnell, 1957), non-
steroidal anti-inflammatory drugs (Kevin et al., 1985),
corticosteroids (Green, 1976), psychological stress
(Pfeffer, 1982), H. pylori infection (Blaser, 1987) and
genetic factors (Doll and Kellock, 1951).
Considering the present status, the antacids provide
symptomatic relief without inhibiting the gastric secretion
or efficiently promoting healing. The H2 receptor blockers
and proton pump inhibitors although decrease the acid
secretion and promote healing of ulcer, but have not
proved their worth in preventing relapse and recurrence.
Also “acid rebound” after cessation of therapy and long
term adverse effects limit their utility. The anticho-
linergics, prostaglandin analogs and ulcer protective
agents are not very effective antiulcer agents. Ulcer
healing drugs like carbenoxolone is associated with
increased mineralocorticoid activity (Laurence, 1996).
Therefore the present therapy is not satisfactory. Aloe
vera derives from the Arabic word "Alloeh" meaning
"shining bitter substance, " while "vera" in Latin means

1868 Afr. J. Pharm. Pharmacol.
"true." 2000 years ago, the Greek scientists regarded A.
vera as the universal panacea. The Egyptians called Aloe
"the plant of immortality." Aloe plants have been used
medicinally for centuries. Among them, Aloe barbadensis
(1,8-Dihydroxy-3-hydroxymethyl-10-(6-hydroxymethyl-
3,4,5-trihydroxy-2-pyranyl anthrone) commonly called A.
vera, is one of the most widely used healing plants in the
history of mankind.
Two distinct preparations of Aloe plants are most used
medicinally. The leaf exudate (Aloe) is used as a laxative
and the mucilaginous gel (A. vera) extracted from the leaf
parenchyma is used as a remedy against a variety of skin
disorders (Capasso and Gaginella, 1997). Aloe leaf
exudate also possesses anti diabetic (Ghannam et al.,
1986) and cardiac stimulatory activity (Yagi et al., 1982).
A. vera also has anti ulcer effect. Anti-ulcer activity may
due to its anti-oxidant activity, anti-inflammatory, mucus
secreting, cyto protective or healing activities.
Therefore, this study was conducted to evaluate the
“anti-ulcer effects of A. vera in non-steroidal anti-inflam-
matory drug induced peptic ulcers in albino rats”.
MATERIALS AND METHODS
Albino rats (Wister strain) of either sex weighing between 150 to
200 gms were used for the study. The study was performed in the
experimental laboratory in the Department of Pharmacology after
obtaining approval from the Institutional Animal Ethics Committee.
Rats were purchased from National Institute of Nutrition,
Hyderabad. The animals were acclimatized for two weeks before
experimentation, they were maintained on synthetic pellet feed
(Pranav Agro Industries Ltd. Sangli, Maharashtra) and clean water
ad libitum. Animals were housed in controlled conditions with
temperature of 25  2°C and 12/12 h light-dark cycle environment;
they were randomly allocated to different experimental groups and
placed in cages with mesh bottom to prevent coprophagy.
Four groups of albino Wister rats six per each group were
selected for the present study. First group was taken as a normal
control group while second group was taken as an indomethacin
induced gastric ulcer control group. In this group, rats were fasted
24 h and then indomethacin was administrated orally through the
gastric gavages (20 mg/kg). The rats were killed 6 h after
indomethacin administration. The stomachs were opened along the
lesser curvature and the stomach were isolated and washed in
normal saline. Then, the stomachs were observed with the help of
magnifying lens, and its external and internal surface was studied
and observed hemorrhage, dilation of blood vessels, ulceration,
perforation, size and number of ulcers and ulcer index was
evaluated according to the severity of ulcers. The stomachs were
stored in the 5% formalin (Vananenn et al., 1991).
Third group was taken as a test (A. vera) group. A. vera powder
was purchased from Madvik Research laboratory Pvt. Ltd. A. vera
powder was mixed with gum acacia and diluted with distilled water.
The prepared solution was administered orally through the gavage
to rats. The pretreatment of A. vera powder was gavaged in the
dose of 200 mg/kg to albino rats (Subramanian et al., 2007). The
treatment schedule was once a day and it was continued for five
days. After completing the five days, rats were kept 24 h fasting and
then indomethacin was given orally, and after 6 h rats were
sacrificed, stomachs were opened and washed with normal saline
and fixed in 5% formalin.
Fourth group was taken as a standard (omeprazole) group; it was
the standard drug for the present study. Propylene glycol was
served as vehicle for omeprazole (20 mg/kg) administered
intraperitoneally (Jagruthi et al., 1997). This treatment was
continued for five days, at the end of the last day rats were kept
fasting for 24 h, after which indomethacin was administered orally,
rats were killed after 6 h, stomachs were opened and washed with
normal saline and stored in 5% formalin solution.
Ulcer indexing (UI)
The dissected stomachs were cut open along the lesser curvature
and the inner surface was examined for ulceration. The open
stomachs were studied by individuals who were blinded for test
drugs and control animals (Adami et al., 1997).
Ulcer number
Total numbers of ulcers in each stomach were noted and petechial
hemorrhage congestion, etc. was also noted.
Ulcer size
With the help of magnifying lens the size of each ulcer measured
along the length of any lesion within 1 mm was taken as pin point.
In indomethacin induced gastric ulcer
Ulcer indexing was done according to the modified scoring system
of adami et al. (1997) as follows: 0 = no lesions, 1 = hemorrhagic
suffusions, 2 = from 1 to 5 small ulcers up to 3 mm size, 3 = many
small ulcers more than 5 or 1 ulcer of more than 3 mm, 4 = many
ulcers of more than 3 mm, 5 = perforated ulcers. The mean scores
for each group were then calculated and the results were analyzed.
Histological studies
A portion of the ulcer region in the stomach was dissected out and
fixed in 5% buffered neutral formalin solution for histological
observations. After fixations, tissues were embedded in paraffin,
solid sections were cut at 5 µm and stained with hematoxylin and
eosin. The sections were examined with the help of a light
microscope and photomicrographs were taken.
Statistical analysis
Data were expressed as mean ± SEM. Statistical analysis was
done using unpaired student „t‟-test. P value 0.05 was
considered statistically significant.
RESULTS
The gastric ulcer control group presented with features of
ulceration. On gross examination, serosal surface of
stomach showed marked indurations, dilated blood
vessels, ecchymosis and hemorrhagic sites (Figure 3b)
when compared with normal control group(Figure 3a).
Mucosal surface presented with features of severe
degree of hyperemia, congestion and large number of pin
point ulcers of varying sizes with central clots and
features of perforation in the stomach. The ulcer index
was U.I ± SEM: 50 ± 3.5. Microscopic features were

100%
40%
20%
0
20%
40%
60%
80%
100%
120%
Control
Aloe vera
Omeprazole
Figure 1. Bar diagram showing percentage of injury in
indomethacin induced gastric ulceration. Percentage of injury in
gastric ulcer control group is 100% and Aloe vera pretreated group
is 40% and omeprazole treated group is 20%.
a. Showing the section of normal rat gastric mucosa
b. Showing the section of indomethacin induced rat gastric mucosal erosion
Figure 2. Histopathological sections of normal rat and
indomethacin induced rat gastric mucosa.
suggestive of acute gastric ulceration with de-
epithelialization (Figure 2b) when compared with normal
control group (Figure 2a). Animals pretreated with A.
vera showed few signs of mucosal injury (Figure 3c), but
Borra et al. 1869
a. Photograph showing normal rat stomach
b. Photograph showing the indomethacin induced ulcers in rat stomach
c. Photograph showing the Aloe vera pretreated rat stomach
Figure 3. Photographs of rat stomach: a; normal, b; indomethacin
induced, c; Aloe vera pretreated.
the percentage of damage was less as compared to
control group (Figures 1 and 3c). Serosal surface
revealed very few dilated blood vessels and
hemorrhages. Mucosal surface revealed few ulcers of
varying sizes. Correspondingly, the ulcer index also was

1870 Afr. J. Pharm. Pharmacol.
reduced, U.I ± SEM: 20 ± 1.79.
Animals treated with omeprazole maintained near
normal pattern. Serosal surface looked amber colour with
few signs of dilated blood vessels and hemorrhagic
suffusions. Mucosal surface retained the normal rugae
pattern with minimal signs of mucosal injury. The ulcer
index was markedly reduced, U.I ± SEM: 10 ± 1.96. Thus,
animals treated with standard drug omeprazole showed
antiulcer activity.
DISCUSSION
In the present study, the anti ulcer effect of A. vera in
non-steroidal anti-inflammatory drug (indomethacin)
induced peptic ulcer was observed. The mean ulcer index
of control group was 50 ± 3.5. In test (A. vera) group,
mean ulcer index was 20 ± 1.79 and the standard
omeprazole treated group mean ulcer index was 10 ±
1.96. The results were statistically significant (P < 0.001).
In most of the cases, non-steroidal anti-inflammatory
drugs like indomethacin and aspirin are known to induce
numerous punctiform and filiform gastric ulcers during the
course of anti-inflammatory therapy and hence,
indomethacin induced model was used in the present
study. Although, the mechanisms underlying the ulcero-
genecity of indomethacin are not completely, but
inhibition of prostaglandin synthesis may be important
(Vane, 1971). This is supported by Ferreira et al. (1974)
study, stating prostaglandins normally have protective
function in the stomach by maintaining gastric micro-
circulation. Magri et al. (2007) reported that prostaglandin
promotes mucus and bicarbonate secretions.
Indomethacin induced gastric damage to rat gastric is
markedly dependent on luminal pH (Elliott et al., 1996).
Gastric damage may potentially facilitate the indome-
thacin induced mucosal damage by two mechanisms: (1)
by enhancing gastric absorption of these drugs or (2) by
amplifying mucosal injury (Yeomans et al., 1992).
The antiulcer activity of A. vera is due to its anti-
inflammatory (Robert et al., 1979), cytoprotective
(Mahattanadul, 1995), healing (Teradaira et al., 1993) anti
oxidant activity and mucus stimulatory effects
(Visuthipanich, 1988). A. vera has anti-inflammatory
effects of leukocyte-endothelium interaction in the gastric
microcirculation of H. pylori infected rats (Prabjone et al.,
2006). The observation that A. vera extract inhibits acid
secretion may be due to the presence of lectins in the
plant (Blitz et al., 1963). Lectins are
proteins/glycoproteins which are capable of recognizing
and binding to carbohydrate moieties (Bardocz et al.,
1995). It has been shown that lectins inhibit aminopyrine
uptake by parietal cells (Healey et al., 1998). Thus, the
ability of the extract to inhibit gastric acid output maybe
as a result of direct action on the acid producing cells.
Administration of A. vera enhance mucous resistance
and resulted in decrease of ulcer index and ulcerated
surface. Aloe buettneri extract increased gastric mucus
production (Kossi et al., 2011). According to Hiruma-Lima
et al. (2006) gastric mucus is a viscous, elastic, adherent
and transparent gel formed by water and glycoproteins
covering the entire gastrointestinal mucosa. These
authors reported that the protective properties of the
mucus barrier depends not only on its gel-like structure,
but are also related to the amount or thickness of the
layer covering the mucosal surface. Mucus protects the
gastric mucosa against irritants, such as ethanol, HCl and
acetyl acid. The cytoprotective action of A. vera may be
due to its active ingredients like tannins, saponins and
flavonoids (Rajasekaran et al., 2005a). The proton pump
inhibitor, omeprazole is having a mechanism of action on
the development of acute ulcers and accelerate the
healing of preexisting ulcers appears to be mainly due to
it‟s potent and long lasting antisecretory activities
(Osamu, 1984). This study suggest that A. vera possess
cytoprotective effects and acid reducing effects like
omeprazole.
Conclusion
A. vera showed statistically significant anti ulcer activity
comparable to standard drug omeprazole. The mean
ulcer indexes of two drugs are formed to be statistically
significant (P value is < 0.001). Therefore, the results
were suggestive of anti ulcerogenic activity of A. vera.
However, the cellular mechanisms for these actions
remain to be established.
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