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     

© A&V Publication all right reserved

Research J. Pharmacology and Pharmacodynamics. 3(5): Sept –Oct. 2011, 256-259