COMPARATIVE EVALUATION OF DIFFERENT DOSES OF VINPOCETINE ALONE AND IN COMBINATION WITH SULFASALAZINE IN EXPERIMENTALLY INDUCED INFLAMMATORY BOWEL DISEASE IN RATS

  • Nishtha Datt Department of Pharmacology, School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
  • Rakesh Raman Patyar Department of Biochemistry, Indira Gandhi Medical College, Shimla, Himachal Pradesh, India
  • Sazal Patyar Department of Pharmacology, School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India

Abstract

 

 Objective: Inflammatory bowel disease (IBD) is a disorder characterized by chronic inflammation of the gastrointestinal tract and its exact etiopathology is still unclear. Most of the currently available drugs provide the symptomatic improvement, and their long-term use can lead to various unwanted effects also. This study was done to observe the effects of vinpocetine alone and in combination with sulfasalazine on IBD in rats.

Methods: Adult Wistar rats of either sex were used (n=36). Experimental colitis was produced by intracolonic administration of acetic acid (10% v/v, 0.20 ml/rat) given per rectally. Rats were divided into six groups (n=6): Group I - normal control (0.9% w/v saline, intracolonic administration + 0.5% w/v carboxymethyl cellulose, i.e., CMC, p.o); Group II - acetic acid (10% v/v, intracolonic administration+0.5% w/v CMC, p.o); Group IIIA - acetic acid + vinpocetine (5 mg/kg, p.o); Group IIIB - acetic acid + vinpocetine (10 mg/kg, p.o); Group IV - acetic acid + sulfasalazine (360 mg/kg, p.o.); Group V - acetic acid + sulfasalazine + vinpocetine (360 mg/kg, p.o. + 5 mg/kg, p.o). The study period was of 15 days in which animals were treated with acetic acid solution on day 1 and treatment was started 4 hrs after the administration of acetic acid till the 14th day. On 15th day, the animals were sacrificed for the investigation of various macroscopic, microscopic, and biochemical parameters.

Results: The higher dose of orally administered vinpocetine (10 mg/kg) and combination of sulfasalazine + vinpocetine (360 mg/kg + 5 mg/kg) were found to be the most effective in reducing the severity of mucosal damage which was similar to the reference drug sulfasalazine (360 mg/kg). Both the doses of vinpocetine curtailed the histopathological scores. The combination therapy of sulfasalazine + vinpocetine (360 mg/kg + 5 mg/kg) was equally effective to standard drug but not found to be the most effective treatment. Myeloperoxidase levels were significantly reduced in vinpocetine treated groups as compared to acetic acid control group, while the glutathione levels were increased significantly. Similarly, vinpocetine significantly decreased the malondialdehyde level in the intestinal tissue of the rats with acetic acid induced colitis, and thus the severity of the tissue damage.

Conclusion: The results of this study indicated that vinpocetine possesses anti-inflammatory activity and are therapeutically effective in acetic acid induced ulcerative colitis at a dose of 5 mg/kg. More pronounced effects were observed at higher dose, i.e., 10 mg/kg. The combination of sulfasalzine + vinpocetine was also found to be effective as compared to high dose of vinpocetine (10 mg/kg).

Keywords: Crohn’s disease, Ulcerative colitis, Diagnosis, Treatment, Chronic disease, Tumor necrosis factor, Myeloperoxidase, Malondialdehyde, Interleukin-1.

Author Biography

Nishtha Datt, Department of Pharmacology, School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
School of Pharmaceutical Sciences, Asst. Prof

References

1. Baumgart DC, Carding SR. Inflammatory bowel disease: Cause and immunobiology. Lancet 2007;369(9573):1627-40.
2. Baumgart DC, Sandborn WJ. Inflammatory bowel disease: Clinical aspects and established and evolving therapies. Lancet 2007;369(9573):1641-57.
3. Sachard D. Planting the seeds of knowledge about inflammatory bowel disease: Half a century of science, prescience and prophecy from the pages of Mount Sinai’s Journal. Mt Sinai J Med 2001;68:79-87.
4. Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature 2007;448(7152):427-34.
5. Lawrence MT, Macphee SJ, Papadakis MA, editors. Current Medical Diagnosis and Treatment. Chicago: McGraw Hill; 2014.
6. Chan AT, Manson JE, Albert CM, Chae CU, Rexrode KM, Curhan GC, et al. Nonsteroidal antiinflammatory drugs, acetaminophen, and the risk of cardiovascular events. Circulation 2006;113(12):1578-87.
7. Kruis W, Schreiber S, Theuer D, Brandes JW, Schütz E, Howaldt S, et al. Low dose balsalazide (1.5 g twice daily) and mesalazine (0.5 g three times daily) maintained remission of ulcerative colitis but high dose balsalazide (3.0 g twice daily) was superior in preventing relapses. Gut 2001;49(6):783-9.
8. Patyar S, Prakash A, Modi M, Medhi B. Role of vinpocetine in cerebrovascular diseases. Pharmacol Rep 2011;63(3):618-28.
9. Jeon KI, Xu X, Aizawa T, Lim JH, Jono H, Kwon DS, et al. Vinpocetine inhibits NF-kappaB-dependent inflammation via an IKK-dependent but PDE-independent mechanism. Proc Natl Acad Sci U S A 2010;107(21):9795-800.
10. Hagiwara M, Endo T, Hidaka H. Effects of vinpocetine on cyclic nucleotide metabolism in vascular smooth muscle. Biochem Pharmacol 1984;33(3):453-7.
11. Abdel Salam OM, Oraby FH, Hassan NS. Vinpocetine ameliorates acute hepatic damage caused by administration of carbon tetrachloride in rats. Acta Biol Hung 2007;58(11):411-9.
12. Ghatule RR, Goel S, Gautam MK, Singh A, Joshi VK, Goel RK. Effect of Azadirachta indica leaves extract on AA-induced colitis in rats: Role of antioxidants, free radicals and myeloperoxidase. Asian Pac J Trop Dis 2012;2:S651-7.
13. Zhang DK, Cheng LN, Huang XL, Shi W, Xiang JY, Gan HT. Tetradrine ameliorates dextran-sulphate-sodium-induced colitis in mice through inhibition of nuclear factor-κB activation. Int J Colorectal Dis 2009;24:5-12.
14. Wirtz S, Neufert C, Weigmann B, Neurath MF. Chemically induced
mouse models of intestinal inflammation. Nat Protoc 2007;2(3):541-6.
15. Kojima R, Kuroda S, Ohkishi T, Nakamaru K, Hatakeyama S. Oxazolone-induced colitis in BALB/C mice: A new method to evaluate the efficacy of therapeutic agents for ulcerative colitis. J Pharmacol Sci 2004;96(3):307-13.
16. Vogel H, editor. Drug Discovery and Evaluation Pharmacological Assay. Germany: Springer; 2002.
17. Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys 1959;82(1):70-7.
18. Krawiesz JE, Sharan P, Stenson WF. Quantitative assay to acute intestinal inflammation based on myeloperoxidase activity: Assessment of inflammation in rat and hamster model. Gastroenterology 1984;87:1344-50.
19. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95(2):351-8.
20. Randhawa PK, Singh K, Singh N, Jaggi AS. A review on chemical-induced inflammatory bowel disease models in rodents. Korean J Physiol Pharmacol 2014;18(4):279-88.
Statistics
231 Views | 389 Downloads
Citatons
How to Cite
Datt, N., R. R. Patyar, and S. Patyar. “COMPARATIVE EVALUATION OF DIFFERENT DOSES OF VINPOCETINE ALONE AND IN COMBINATION WITH SULFASALAZINE IN EXPERIMENTALLY INDUCED INFLAMMATORY BOWEL DISEASE IN RATS”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 10, no. 16, Sept. 2017, pp. 88-93, doi:10.22159/ajpcr.2017.v10s4.21343.
Section
Original Article(s)