INTRODUCTION:
Gastric ulcer is one of the most prevailing gastrointestinal
disorders, which affects approximately 5-10% of people during their life. A
peptic ulcer is a sore on the lining of the stomach or duodenum, which is the
beginning of the small intestine1. Peptic ulcer represents a major
health problem, both in terms of morbidity and mortality. Research advancement
during the last few years have offered new insights in the therapy and
prevention of gastroduodenal ulcerations, by measures
directed at strengthening the mucosal defense system rather than by attenuating
the aggressive acid-pepsin factors held responsible for the induction of ulcers2.
In addition to
the various causes of peptic ulcers - a collective term used for both gastric
and duodenal ulcers, role of free radicals has also been implicated in the
etiology of ulcers in addition to several other diseases such as liver
cirrhosis, atherosclerosis, cancer, aging, arthritis, diabetes and the
compounds that can scavenge free radicals have great potential in ameliorating
these disease processes.
Commicarpus chinensis is commonly known as Gum fruit. It belongs
to the family Nyctaginaceae3. The synonyms are Boerhavia
chinensis, Boerhavia repanda, and Valerian chinensis4.
The plant is commonly also known as diffuse hogweed, Punarnava
Pungli (in Marathi) and Theega
mamidi (in Telugu).4 Commicarpus
chinensis has been used in various ayurvedic and siddha preparations
for its hepatoprotective, gastroprotective,
useful in Down’s syndrome, analgesic, antipyretic and anti-inflammatory properties3.
The aqueous extract of C.chinensis leaves,
contains large amount of flavonoids, saponins and phenolic compounds,
exhibits high antioxidant and free radical scavenging activities. It also
scavenges NO and DPPH free radicals and has reducing power.3 The in
vitro assays indicate that this plant extract is a significant source of
natural antioxidant, which might be helpful in preventing the progress of
various oxidative stresses. Parts of C. chinensis plant has been included in various
treatments, like the roots are
used for edible purpose for its nutritional properties5 and used in
treatment of skin diseases.6 The plant posses diuretic activity.7
Traditionally the Roots are taken orally for its antihelmintic, leucorrhea, and Galactoseamine and paracetamol
intoxication effects.3
Phytochemical investigation of the plant revealed that the plant contains
carbohydrates, monosaccharide, amino acids, steroids, saponins
glycosides, tannins, phenolic compounds, flavonoids.3
Therefore, the present study was conducted to evaluate the gastroprotective
activity of leaf extract of C. chinensis by
using ethanol and aspirin induced ulcer models generating free radicals to
induce ulcers.
MATERIALS AND METHODS:
C.chinensis plants were collected from the campus of Gulbarga
University, Gulbarga, Karnataka. During the collection
of a plant, care was taken to ensure that plants to be collected were healthy
as diseases and infections may change the efficacy and properties of
metabolites produced by the plants. Following the collection, the plants were
authenticated by Department of Botany. Wistar albino rats of either sex
weighing between 180-220g were used and purchased from the local licensed
dealer. The animals were allowed acclimatize in laboratory conditions for a week
prior to the beginning of the experiment. During the acclimatization period the
animals were fed with standard food pellets (Hindustan Pvt. Ltd., Mumbai) and
water ad.libitum.
Preparation
of Extracts:
The plant material was shade dried and coarsely powdered. Coarsely
powdered material was subjected to extraction using soxhlet
apparatus. Distilled water was used as a solvent. The powdered material was
evenly packed in extractor for 36h with distilled water. The temperature of the
electric heating mantle was maintained using thermostat control. Appearance of
colorless solvent in the siphon tube is considered the end of extraction
process. The extract was concentrated by distillation process. The extract was
air dried at room temperature and weighed.
Ethanol induced ulcers2:
Albino wistar rats of either sex weighing between 180 – 220g
were divided into 3 groups of 6 animals each.
Group I –
Control
Group II-
Standard (Rabeprazole 0.36mg/200gm b.w., p.o.)
Group
III- Aqueous extract of C.chinensis
(100mg/200gm b.w., p.o.)
The rats were
fasted for 48h. Care was taken to avoid coprophagy.
At the end of 48h, the animals were administered with the selected drugs. After
2h of drug administration, absolute ethanol (1ml/200gm b.w.,
p.o.) was administered to the rats of all the Groups
(I to III) to induce ulcers. After 4h of ethanol administration, the rats were
euthanized and stomachs were excised out.
Aspirin
induced ulcers:
Wistar albino
rats weighing 180–220g were used. The selected drugs are administered orally as
per the sequence mentioned above, 30 min prior to oral aspirin in a dose of
200mg/kg suspended in 1% CMC. 4h later, the rats are sacrificed and their
stomachs were removed. Formol-saline (2% v/v) is then
injected into the totally ligated stomachs for
storage overnight. The next day, the stomachs are opened along the greater
curvature, then washed in warm water and examined under a 3-fold magnifier.
Ulcer index and percentage protection were evaluated.
Determination
of ulcer index9:
The stomachs were
opened along the greater curvature and washed under running water to see
for ulcers in the glandular portion of the stomach. The number of ulcers
per stomach was noted and scoring was done microscopically with
the help of hand lens (10X)
0 = Normal stomach
0.5 = Red
coloration
1.0 = Spot
ulcers
1.5 =
Hemorrhagic streaks
2 .0 = Ulcer
≥ 3 ≤ 5
3.0 = Ulcer >
5
Mean ulcer score
for each animal is expressed as ulcer index and the percentage protection was
calculated by using the formula10:
UI Control – UI
Test
% Protection =
X 100
UI
Control
Statistical
analysis:
Results were
expressed as mean± SEM, (n=6). Statistical analysis was performed using
one way ANOVA by Dunnett’s test. P value less
than 0.05 was considered to be statistically significant. *P<0.05,
when compared with standard rabeprazole and
treatment group as applicable.
RESULTS:
The aqueous
extract of C.chinensis exhibited significant antiulcer effect
by indicating percentage protection of 64.5% in ethanol induced ulcer model (table.1) and 65.6% in aspirin induced
ulcerations (table.2). The antiulcer
effect may due to the antioxidant property of the plant due to the presence of flavonoids, saponins and tannins.
Table.1: effect of C.chinensis on ulcer Index in
ethanol induced ulcers.
|
Treatment Groups |
Ulcer Index |
% Protection |
|
Control |
5.167± 0.16 |
------ |
|
Standard |
0.8333± 0.10 |
83.8 |
|
Aqueous extract |
1.833± 0.10 *** |
64.5 |
Values are the
Mean± S.E.M, n=6, Significant *P <0.05 compared with Standard
Table.2: Influence of C. chinensis on ulcer Index in Aspirin
induced ulcers.
|
Treatment Groups |
Ulcer Index |
% Protection |
|
Control |
5.583±0.15 |
------ |
|
Standard |
1.083±0.08 |
80.6 |
|
Aqueous extract |
1.917±0.08 *** |
65.6 |
Values are the
Mean± S.E.M, n=6, Significant *P <0.05 compared with Standard
DISCUSSION:
Many natural
products and modern synthetic drugs have been used to treat the peptic ulcer
disease but so far a complete cure has not been discovered and exploration of
new antiulcer drugs has remained a field of active research. Different types of
antiulcer agents are being prescribed to overcome the disease problem. For
example, a natural product sucralfate that binds to proteinaceous materials in the ulcer crater and prevents
further digestion of the mucosa by gastric acid and pepsin has been tried.
Similarly, colloidal bismuth salt that forms a precipitate and binds to the
surface of ulcer to provide a barrier against corrosive effects of gastric acid
and pepsin has been used11. Many antacids that neutralize gastric
acid and anti-cholinergic agents that decrease acid secretion by blocking
parasympathetic activity have long been used12. The modern drugs
like proton pump inhibitors like omeprazole, lansoprazole and rabeprazole
de-crease the gastric acid secretions from parietal cells13,14. Metronidazole and antibiotics such as amoxicillin
and clarithromycin have also been used to treat the
peptic ulcers in different combinations as double, triple and quadruple therapy
regimens15-18. Despite all these developments, recurrence of peptic
ulcer disease occurs even after long term therapy.
The aim of the
present study was to investigate the antiulcer effect of the C.chinensis on
the gastric secretion activities such as ulcer index and percentage protection
using the ethanol and aspirin induced ulcer models. The results revealed that
the aqueous extract of C.chinensis exhibited an effective antiulcer and gastroprotective effect in both the models by reducing the
ulcer index significantly (Fig.1 and
Fig.2).
Among the
various causes of gastric ulceration lesions caused by stress, alcohol, H.pylori and due
to use of NSAIDs have been shown to be mediated largely through generation of
reactive oxygen species (ROS), especially the hydroxyl radical. A number of
excellent drugs, developed over the decades have proven useful in controlling
hyperacidity and ulceration but their long term use is reported to have various
side effects. Hence the investigations continue with an objective to find a
therapy with more efficacy and lesser side effects. Role of free radicals has
been implicated in the cause of several diseases such as liver cirrhosis,
atherosclerosis, cancer, aging, arthritis, diabetes. Compounds that can
scavenge free radicals have great potential in ameliorating these disease
processes are known as antioxidants. It is therefore worthwhile to study well
defined antioxidants for their usefulness as gastroprotective
agents. The considerable growth in the
use of herbal medicine in both developing and developed countries even with or
without experimental evidence on animal necessitates an immediate study of
components used in many herbal preparations. Preliminary phytochemical
screening of the extract of the leaves revealed that C.chinensis exhibited the
presence of steroids, tannins, flavonoids, saponins, carbohydrates and proteins. The in vitro evaluation of antioxidant
properties of Commicarpus chinensis of
leaf extract and the antihepatotoxic activity of Boerhavia repanda
was reported. C.chinensis may act by
inactivating the ROS by exchanging the electrons and neutralizing the free
radicals due to the presence of flavonoids, saponins and tannins which are known to impart antioxidant
properties to most of the plants.
Figure.1: Ulcer
index of C.chinensis in ethanol induced ulcers.
Figure.2: Ulcer
index of C.chinensis in aspirin induced ulcers.
CONCLUSION:
The aqueous leaf
extract of C. chinensis
exhibited significant antiulcer property. Thus, it is a potent gastroprotective agent with known antioxidant property.
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Received on 16.04.2014 Accepted on 28.06.2014
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Press All Right Reserved
Asian J. Pharm.
Res. 4(3): July-Sept. 2014;
Page 119-122