Antisecretory
and Antiulcer Activity of Cartaeva nurvala against Indomethacin plus Pyloric
Ligation Induced Gastric Ulcers in Rats.
Gauri Karwani*, Indrajeet Singhvi and Santosh
Gupta
Pacific
College of Pharmacy, Pacific Hills, Airpoart Road, Pratapnagar
Extension,Udaipur , Rajasthan, India.313001
ABSTRACT:
Aims: To study the anti-secretory
and anti-ulcer activity of cartaeva nurvala
(ethanolic extract) and its action against indomethacin plus pyloric
ligation induced gastric ulcers in rats.
Settings and Design:.Rats treated with two oral doses of indomethacin suspension as a
standard dose, at an interval of fifteen hours, two hours after the second dose
of indomethacin , Pyloric ligation was carried the rats were destroyed by
over-dose of anesthetic ether. Pyloric ligation was done only to collect the
gastric content for analysis.
Methods and Material: Indomethacin plus
pyloric ligation (PL) induced gastric ulceration model was used in the study.
Statistical analysis used: The results were
expressed as mean ± SEM. The significance of difference
between mean values for the various treatments was tested using the unpaired
student ‘t’ test P< 0.05 was considered
statistically significant.
Results: Treatment from cartaeva nurvala crude extract for fifteen days significantly reduced ulcer
index when compared with control group. Crude extract also significantly
reduced volume of gastric secretion, free acidity and total acidity. A
significant increase in total carbohydrate (TC) and TC / total protein (TP)
ratio of gastric juice was also observed. No significant change in the total
protein was noted.
Conclusions: cartaeva nurvala was found to be an effective
anti-ulcerogenic agent, whose activity can well be compared with that of
ranitidine hydrochloride.
KEY-WORDS: Anti-ulcer activity, cartaeva nurvala, Indomethacin plus PL
KEY MESSAGES: The present study thus confirms anti-ulcer
and anti-secretory effects of cartaeva nurvala in indomethacin
induced gastric lesions.
INTRODUCTION:
Peptic ulcer is a
gastrointestinal disorder that requires a well targeted therapeutic strategy. A
number of drugs including proton pump inhibitors and H2 receptor antagonists
are available for the treatment of peptic ulcer. This is the rationale for the
development of new anti-ulcer drugs, and the search for novel molecules has
been extended to herbal drugs that would offer better protection and decreased
relapse.1 The genus Crataeva
(Capparidaceae) is named in honor of the Greek botanist Crataevas. Crataeva
nurvala is commonly known as barna and varuna2 and distributed,
throughout India and tropical regions of the world wild or cultivated3.
MATERIALS AND METHODS:
Chemicals
Indomethacin (Bombay tablet
Mfg. co., Gandhinagar); Carboxy Methyl Cellulose (CMC; Apex Chemicals, Mumbai)
and Diethyl Ether (Alembic Chemicals work Ltd., Baroda).
Animals:
Adult (one and half month old, bodyweight 225 to 275 g) albino rats (Wistar strain) of the either sex were
used in the present study. The animals were acclimatized for ten days in
polyutharine cages in laboratory conditions. All the rats were fed with standard
laboratory diet and given water ad
libitum. Care was taken to avoid coprophagy. The animals were maintained
per CPCSEA (Committee for the Purpose of Control and Supervision of Experiments
on Animals) regulations and the experiment was cleared by IAEC (Institutional
Animal Ethics Committee).
Plant Collection:
The whole plant of Crataeva nurvala was collected from a rural area near Udaipur
(Rajasthan) city.
EXTRACTION OF PLANT
MATERIAL:
The Crataeva nurvala plant was dried under
shade and then powdered with a mechanical grinder to obtain a coarse powder
(500 gm) the fine powder of whole plant was packed in high quality filter
paper, which was then subjected to successive extraction in a soxhlet apparatus
using 95% ethanol for about 72 hour, solvent was recovered. After vacuo
evaporation the crude extract was dispersed in distilled water with suspending
agent CMC.
Indomethacin
plus pyloric ligation (PL) induced gastric ulceration model:
Rats were fasted for 12 hours, and treated
with two oral doses (2X10 mg/kg) of indomethacin suspension (in 0.5% CMC made
in water) as a standard dose, at an interval of fifteen hours, two hours after
the second dose of indomethacin, PL was carried out 4 as per the
method of Shay et al 5. Four hours after ligation, the rats were
destroyed by over-dose of anesthetic ether. Pyloric ligation was done only to
collect the gastric content for analysis. The stomach was dissected out by its
greater curvature and contents were drained into sterile tubing. The inner
surface of the empty stomach was examined for gastric lesions.
Experimental
groups:
Rats were divided into four groups
Containing four animals in each group:
Group 1: Rats were given only vehicle (0.5%
CMC) each day upto 15 days.
Group 2: Rats were treated with two oral doses
(2X10 mg/kg) of indomethacin suspension (in 1.0% CMC made in water) as a standard dose, at an
interval of fifteen days.
Group 3: Rats were given indomethacin plus Crataeva nurvala (100 mg/kg/day, bw, p.o.) for 15 days.
Group4:Rats were given indomethacin plus
Ranitidine (30 mg/kg/day, bw, p.o.) for 15 days.
On day 16th PL was performed and
rats were sacrificed and stomachs were removed. Ulcer index6, volume
of gastric secretion18, free acidity and total acidity 7,
total carbohydrate (TC) content 8 and total protein (TP) content 9
and TC/TP ratio of gastric juice were estimated.
Statistical
Analysis:
The results were expressed as mean ± SEM
.The significance of difference between mean values for the various treatments
was tested using unpaired t test. The level of significance was P < 0.05 10.
RESULTS:
The results of drug treated animals were
compared with indomethacin treated animals – Figure - 1 (a - b) shows the
effect of extract on ulcer index and volume of gastric secretion in the
experimental animals. In-group II animals treated with indomithacin on volume
of gastric secretion (2.860 ± 0.236) is significantly higher when compared with
group I only vehicle treated animals. In group III and group IV of animals
treated with Cartaeva nurvala and
Ranitidine respectively on the volume of gastric secretion (2.380 ± 0.060,
1.960 ± 0.230) was significantly reduced. In group II animals ulcer index was
significantly higher (5.977 ± 0.520) when it was compared with group I but in
group III and group IV the ulcer index was significantly reduced (3.390 ±
0.660; 1.960 ± 0.230 respectively) (Figure - 1; b). The crude extract of Cartaeva
nurvala significantly decreases free acidity (10.98 ± 1.097) and total
acidity (37.82 ± 3.020) (Figure-2; a - b) and significantly increases total
carbohydrate (TC) content (424.000 ± 8.510) (Figure – 3; a - b) and TC/TP ratio
(1.087 ± 0.080) (Figure – 4) of gastric juice. No significant effect on the TP
has been observed (Figure 3; b).
Figure
1a and 1b: Effect of Cartaeva nurvala extract on ulcer Index (a) and
gastric secretion (b). All values are represented as mean ±
SEM (n = 6).0
Figure:
1(a)
Figure:
1(b)
P
Values: +++ < 0.001 When compared with control
untreated animals
*** < 0.001 When compared with
indomethacin induced animals
Figure
2a and 2b: Effect of Cartaeva nurvala extract on Free acid (a) and total acid (b).
All values are represented as mean ± SEM (n = 6).
Figure:
2(a)
Figure:
2(b)
P
Values: +++ < 0.001 When compared with control
untreated animals
*** < 0.001 When compared with
indomethacin induced animals
Figure
3a and 3b: Effect of Cartaeva nurvala extract on carbohydrate (a) and total protein
(b). All values are represented as mean ± SEM (n = 6).
Figure: 3(a)
Figure:
3(b)
P
Values: +++ < 0.001 When compared with control
untreated animals
*** < 0.001 When compared with
indomethacin induced animals
Figure
4: Effect of Cartaeva nurvala extract on free carbohydrate and total protein
ratio. All values are represented as mean ± SEM (n
= 6).
P
Values: + < 0.05 When compared with control untreated animals
* < 0.05 When compared with indomethacin
induced animals
DISCUSSION:
Results of the study suggest that the
extract can be used for the prevention and treatment of gastric ulcers. In this
study, fifteen days treatment with administration of NSAIDs such as
indomethacin followed by pyloric ligation produced severe gastric lesions in
the rat’s stomach. Indomethacin has been shown to inhibit gastric bicarbonate
secretion In vitro 11.
Increased gastric acid secretion is strongly implicated in development of
gastric ulcers by anti-inflammatory drugs 12. Present investigation
also confirmed the crucial role of hydrochloric acid in ulceration.
Indomethacin and PL induced lesions were associated with significant increase
in volume of gastric secretion, free and total acidity of gastric juice, and
decrease in TC and TC/TP ration.
Non-steroidal anti - inflammatory
drugs (NSAIDs) are widely used in the treatment of pain, fever and
inflammation 25. However, these drugs have some side effects,
especially on the gastrointestinal tract. NSAIDs like indomethacin inhibits COX
- 1 thereby inhibits the prostaglandin synthesis, consequently lipooxygenase
pathway is enhanced liberating leukotrienes and these leukotrienes are reported
to have a role in ulcerogenesis. In addition there is some evidence that NSAIDs
may induce ulcer by causing the back diffusion of H+ ion in to mucosal cells. Therefore the gastroprotective effect of the test extract
may be due to its ability to inhibit the synthesis of
prostaglandins/leukotrienes 13.
Administration of crude extract of Cartaeva
nurvala daily for fifteen days showed significant decrease in gastric
volume secretion, ulcer index, free acidity and total acidity of gastric juice
in all experimental animal models, suggesting antisecretory and antiulcer
effect of the drug. Treatment with crude extract of Cartaeva nurvala
daily for fifteen days showed significant increase in TC and TC/TP ratio of
gastric juice. Increase in TC/TP ratio is important for evaluating antiulcer
activity 14,15 by effect on the mucus formation in the stomach.
The present study thus confirms antiulcer
and antisecretory effects of Cartaeva
nurvala in indomethacin-induced gastric lesions. In our opinion, Cartaeva nurvala causes inhibitory
effects on the release of gastric hydrochloric acid, to protect against gastric
mucosal damage. However, more studies are necessary to show the reproducibility
of our results.
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Received on 02.06.2011
Accepted on 29.06.2011
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Research J. Pharmacology and Pharmacodynamics. 3(5): Sept
–Oct. 2011, 256-259