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RESEARCH ARTICLE
Year : 2009  |  Volume : 5  |  Issue : 18  |  Page : 111-114 Table of Contents     

Anti-inflammatory activity and effect on gastric acid secretion of Azelain isolated from Rhododendron dauricum Linn.


Sri Sai Institute of Pharmaceutical Education & Research, Badhani, Pathankot, India

Date of Submission10-Nov-2008
Date of Decision05-Dec-2008
Date of Acceptance29-Jan-2009
Date of Web Publication30-Dec-2009

Correspondence Address:
Ramnik Singh
Sri Sai Institute of Pharmaceutical Education & Research, Badhani, Pathankot
India
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Source of Support: None, Conflict of Interest: None


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   Abstract 

The effect of Azelain isolated from Rhododendron dauricum Linn. (Ericaceae) on gastric acid secretion in rats was investigated at a dose of 40 mg/kg, while its anti- inflammatory effect was investigated in two experimental models: arthritis induced by Freund's adjuvant carrageenan and cotton pellet induced granuloma. Azelain did not inhibit gastric acid secretion, suggesting that its anti ulcerogenic effect can be attributed to its action on the mucosa defense factors. On the other hand, Azelain inhibited both chronic and acute adjuvant carrageenan induced inflammation phases, being most effective in the chronic phase. In the granuloma test, Azetain also inhibited inflammation. It is suggested that the anti inflammatory activity of Azelain may be attributed to interference with multiple targets on the level of transcription factors, such as NF-kB and cytokines.

Keywords: Anti-inflammatory, Azelain, Gastric acid, Rhododendron dauricum


How to cite this article:
Singh R, Rao HS. Anti-inflammatory activity and effect on gastric acid secretion of Azelain isolated from Rhododendron dauricum Linn. Phcog Mag 2009;5:111-4

How to cite this URL:
Singh R, Rao HS. Anti-inflammatory activity and effect on gastric acid secretion of Azelain isolated from Rhododendron dauricum Linn. Phcog Mag [serial online] 2009 [cited 2020 Jul 15];5:111-4. Available from: http://www.phcog.com/text.asp?2009/5/18/111/57967


   Introduction Top


Rhododendron dauricum Linn. is an evergreen shrub, belonging to the family Ericaceae and is widely distributed in India, China, Korea and Japan. It is used as antibacterial, antifungal and anti-inflammatory in Ayurveda. Its decoction is used to cure skin diseases, inflammation and bronchitis in folk medicine [1] . Earlier, we observed that the aqueous extract of leaves of Rhododendron dauricum Linn. exhibited inhibition of carrageenan-induced rat paw oedema and analgesic activity [2] . Further, the possible role of TNF-α has been elucidated in the anti-inflammatory activity of the plant [3] . In the present work, we investigate the effect of Azelain on the gastric acid secretion of rats, using the technique of ligated pylorus [4] , and evaluate the anti inflammatory activity in two experimental rat models: acute and chronic paw inflammation induced by Freund's complete adjuvant carrageenan- induced [5] and cotton pellet induced granuloma [6] .


   Materials and Method Top


Plant Material

The leaves were collected from Dalhousie, District Chamba, Himachal Pradesh, India. The plant samples were identified and authenticated in the Herbarium, by Dr. N. N. Sharma. A voucher specimen RD-11 was deposited in the Department of Pharmacognosy, Sri Sai Institute of Pharmaceutical Education and Research, Badhani, Pathankot. Azelain was isolated from the dried leaves of Rhododendron dauricum Linn. and confirmed by various spectroscopic methods.

Animals

Albino rats (Wistar strain),of either sex, weighing 150-­200g were used in these experiments Animals were provided with standard food and water ad libitum and were maintained at a constant temperature of 22 ± 1° C (12 hr light and dark cycle) with humidity of 55 ± 5%. Procedures involving animals and their care were conducted in conformity with Committee for the Purpose of Control and Supervision of Experiments on Animals (Regd. No.911 /ac/95/CPCSEA).

Effect of Azelain on the gastric acid secretion in rats Technique of Pylorus ligation

Albino rats, weighing 150-160 g were placed in individual cages with bottoms to prevent coprophagy. The animals were kept under standard conditions at 22± 1 °C with water ad libitum and deprived of food for 24 h before the experiments. The technique of tigated pylorus was used (4). After anaesthetizing with ether, an incision was made in the abdomen and the ligature was performed 0.5-0.7 mm below the pylorus. Care was taken not to damage the blood supply. Immediately after, the animals were separated into four groups. After closing the incisions, Group I (control) and Group 2 were orally administered with 1ml of the carboxy-methylcellulose vehicle (0.4% CMC) in saline and 1 ml of Azelain 40 rng /Kg, respectively. Group 3 and 4 were each intraduodenatly administered with 3 and 30 mg/Kg of ranitidine respectively (dose volume: 5 ml/Kg), plus oral administration of 1 ml of the vehicle. All animals were placed in their cages and deprived of water and food for the rest of the experiment. The animals were sacrificed and 4h later, a ligature was placed at the oesophago-cardiac junction and the stomach was removed. The gastric content was collected and centrifuged, supernatant volumes were measured and the acid concentration was estimated by titration to pH 7.0 with 0.1N sodium hydroxide, using an automatic titrator.

Assessment of anti- inflammatory activity

Activity of Azelain in the adjuvant carrageenan induced inflammation model

Adjuvant carrageenan induced inflammation in rats was used [5] . Albino rats of either sexes, weighing 180 -190g with food and water ad libitum, received an injection of 0.1 ml Freund's complete adjuvant (Sigma) intradermally at the base of the tail. Six days after the adjuvant inoculation, the animals were divided into seven groups of six rats each. All groups were intraperitoneally injected and treated as follows:

Group 1(inflammation control) received an injection of the vehicle (carboxy-methylcellulose, 0.4% CMC) in saline solution and Group 2 received (injection) phenylbutazone (PBZ) at 80 mg/kg (reference drug) Group 3-7 received Azetain doses of 2.5, 5.0, 10.0, 20.0 and 40.0 mg/kg respectively. One hour after dosing, all groups were injected with 0.1 mt per rat of carrageenan type IV w/v 2% (Sigma) in saline solution in the sub-plantar region of the left hind paw. Pedal oedema was determined by measuring the paw volume at 3, 5, 24, 48, 72 and 96 h after carrageenan administration using a plethysmograph [7] . The drug under study and the reference drug were daily administered until the end of the experiment. The oedema volume was expressed as the difference between the left and right hind paw volume. The inhibition percentage of each group was calculated against the control, considered as 100 % inflammation.

Effect of Azelain in cotton pellet-induced inflammation model

Albino rats of either sex, weighing 160-180 g, were used by cotton pellet granuloma method [5] . Granuloma was induced by subcutaneous implant of a sterile cotton pellet (50 mg ) in the dorsal area of anaesthetized rats. Twenty four hours after the implant , animals were divided into four groups and inoculated as follows : Group 1 (control) received subcutaneously (s.c) 0.4% CMC in saline solution Group 2 (reference) was injected (s.c) with dexamethasone (7mg/kg) and Group 3 and 4 received Azelain (40mg/kg) suspended with 0.4% CMC in saline solution by subcutaneous and oral routes, respectively. At the end of experiments, the animals were anaesthetized and the granulomas were removed and weighed. The anti inflammatory effect was assessed by degree of inhibition of the granuloma weight in the groups under study as compared with the control. The granuloma inhibition percentage for each group was calculated by comparison with the control group considered as 100 of inflammatory activity.

Statistical Analysis

The experimental data obtained were expressed as the mean ± S.E.M. The significance of the values in treated groups compared with the control were determined using Student's t-test and Dunnet's test [10],[11] . A probability of P<0.05 was considered significant.


   Results Top


Effect of Azelain on Gastric acid secretion

The results obtained in the pylorus ligated assay [Table 1] showed that Azelain did not inhibit the gastric secretion in rats. The volume of gastric content was significantly increased. On the other hand 30mg/kg dose of ranitidine significantly inhibited the acid concentration and the volume of gastric content.

Evaluation of the anti- inflammatory activity

Adjuvant carrageenan- induced inflammation in the acute phase: the maximum effect of oedema inhibition was obtained after 3 and 5 h of treatment [Table 2] at a dose of Azelain of 40 mg/kg (22 and 34 % respectively), while PBZ inhibited 21 and17 respectively . Doses of 2.5 and 5.0 mg/kg led to non­significant inhibition of 4 and 6% after 3 and 5h respectively. In the chronic phase [Table 3], all the Azelain doses significantly decreased the oedema. The maximum effect of inhibition was obtained after 72 and 96 h of Azelain treatment with a dose of 40 mg/kg (53 and 41% respectively) while PBZ values were 46 and 50 % respectively. In the model of cotton pellet induced granuloma [Table 4] Azelain significantly inhibited the granuloma development: the subcutaneous route was more effective (35.6 inhibition) than the oral route (19.5% inhibition).


   Discussion and Conclusions Top


In the ligated pylorus technique, it was observed that Azetain did not inhibit gastric acid secretion at 40 mg/kg so azelain might favours one of the defense factors of the rat gastric mucosa by increasing gastric gtycoproteins. This suggests that the anti ulcerogenic effect of Azelain against different necrotizing agents may be due to a cytoprotective activity. Histamine (H2) receptor antagonists and proton pump (H + , K + ) ATPase inhibitors suppress gastric acid secretion and secondarily include hypergastrinemia. Sustained hypergastrinemia has atrophic effect on the fundic mucosa, resulting in enterochromaffin like ECL cell hypertrophy and hyperplasia [8] Therefore, it is of interest that Azetain exerts an effective anti­ulcerogenic action without modifying gastric acid secretion.

As regard the anti inflammatory activity of Azelain, the experimental model of inflammation has an acute and a chronic phase and has been proposed as a suitable and simple model system for evaluating potential anti arthritic agents. Azelain was effective in suppressing pedal oedema in the acute as well as in the chronic stage [2] . In the granuloma test, Azelain led to a significant inhibition, with the highest effect being obtained by subcutaneous route and the activity may be attributed to interference with multiple targets on the level of transcriptions factors such as NF-kB and cytokines [9] .

In conclusion based on the results of our study, at the dose effective as anti- ulcerogenic in rats, Azelain does not inhibit the secretion of gastric acid, but shows an anti-inflammatory effect in the acute and chronic phases, being most effective in the latter. The anti inflammatory effect shown here for Azelain, the active principle of Rhododendron dauricum Linn., validates the use of this plant in folk medicine and suggests its potential as a source of an anti- inflammatory agent with gastric cytoprotective properties.

 
   References Top

1.R. N. Chopra, I. C. Chopra and B. Verma. Supplement to Glossary of Indian Medicinal Plants. (Council of Scientific& Industrial Research, New Delhi; 1969) p. 87.  Back to cited text no. 1      
2.H. S. Rao, B. Singh and R. Singh. Analgesic and anti­inflammatory activity of aqueous extract of leaves of Rhododendron dauricum Linn. Scientific Abstracts (CP-80): 58th IPC, Mumbai (2006).  Back to cited text no. 2      
3.H. S. Rao, B. Singh, N. Singh and R. Singh. Anti-inflammatory properties of Rhododendron dauricum Linn. Inhibition of lipopolysaccharide induced septic shock and vascular permeablitiy. Phcog Mag.12(3):233-236 (2007).  Back to cited text no. 3      
4.H. Shay, S.A. Kamarrov, S. Fels, D. Meranzse, M. Gruenstein, and H. Speilt. A simple method for the uniform production of Gastric Ulceration in the rat. Gastroenterology. 5: 43-51(1945).  Back to cited text no. 4      
5.Y. Mizushima, W. Tsukada and to Ankimoto. A modification, of rat adjuvant arthritis for testing anti rheumatic drugs. Journal of Pharmacy& Pharmacology. 24: 781-785 (1972).  Back to cited text no. 5      
6.Meier R, Schuler W, Desaullis P. Zur frage de mechanisus der Hemmung des Bindegewebswachstums durch Cortisone. Experientia.6:468-471 (1950).  Back to cited text no. 6      
7.Slowing K, Carretero E, Villar A. Anti inflammatory activity of Leaf extracts of Eugenia jambos in rats. Journal of Ethnopharmacology. 48: 9-11 (1994).  Back to cited text no. 7      
8.Hakanson R, Telmans Y, Chen D, Anderson K, Rytrerg B, Mattuson H, Sundler F. The biology and pathobiology of the ECL cells. Yale Journal of Biological Medicine. 65:761-774 (1992).  Back to cited text no. 8      
9.Bork PM, Lienhard Schrntz M, Kunth M, Escher C, Heinrich M. Sequiterpene lactones containing Mexician Indian medicinal plants and pure sesquiterpene lactones as potent Inhibitors of transcription factor NF-kB. Federation of European Biochemical Societies. 402: 85-90 (1997).  Back to cited text no. 9      
10.R. Gennaro, The Science and Practice of Pharmacy, 19th ed, Vol. 1, (Mack Publishing Company, Easton PA, 1995), p.11.  Back to cited text no. 10      
11.W. Dunnet. New tables for multiple comparisons with a control. Biometrics. 20:482-91 (1964).  Back to cited text no. 11      



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]


This article has been cited by
1 The genus Rhododendron: An ethnopharmacological and toxicological review
Popescu, R. and Kopp, B.
Journal of Ethnopharmacology. 2013; 147(1): 42-62
[Pubmed]



 

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