Document Type : Original Article

Authors

1 Department of Pathobiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

2 Department of Pathology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

3 Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

Abstract

Crocin, as a carotenoid compound of saffron, exerts a potent antioxidant property. Mesalazine is frequently used in the treatment of ulcerative colitis. This study investigated the effects of separated and combination treatments with crocin and mesalazine in a rat model of ulcerative colitis. Ulcerative colitis was induced by intra-colonic administration of acetic acid (4.00%, 1.00 mL) at 8 cm proximal of the anus. Normal saline, acetic acid, crocin (5.00, 10.00 and 20.00 mg kg-1), mesalazine (100 and 300 mg kg-1) and crocin (5.00 mg kg-1) plus mesalazine (100 mg kg-1) were administered after induction of colitis for eight days. Body weight, oraganosomatic index (OSI), macroscopic and microscopic evaluations of colon and measurement of malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosis factor-alpha (TNF-α) contents of colon tissue were determined on day eight after induction of colitis. Crocin (10.00 and 20.00 mg kg-1), mesalazine (300 mg kg-1) and crocin (5.00 mg kg-1) plus mesalazine (100 mg kg-1) significantly (p < 0.05) improved body weight and OSI and reduced macroscopic and microscopic scores. These treatments also significantly (p <0.05) recovered the increased levels of MDA and TNF-α as well as the decreased level of SOD in colon tissue. Crocin and mesalazine did not produce significant effects in intact rats. Based on the results, it is concluded that crocin and mesalazine produced protective effects on colon tissue via antioxidant and anti-inflammatory actions. In addition, a synergistic effect was observed between crocin and mesalazine in attenuating ulcerative colitis.

Keywords

Main Subjects

  1.  

    1. Bukhari SI, Manzoor M, Dhar MK. A comprehensive review of the pharmacological potential of Crocus sativus and its bioactive apocarotenoids. Biomed Pharmacother 2018; 98: 733-745.
    2. Christodoulou E, Kadoglou NP, Kostomitsopoulos N, et al. Saffron: A natural product with potential pharma-ceutical applications. J Pharm Pharmacol 2015; 67(12): 1634-1649.
    3. Rameshrad M, Razavi BM, Hosseinzadeh H. Saffron and its derivatives, crocin, crocetin and safranal: a patent review. Expert Opin Ther Pat 2018; 28(2): 147-165.
    4. Alavizadeh SH, Hosseinzadeh H. Bioactivity assessment and toxicity of crocin: A comprehensive review. Food Chem Toxicol 2014; 64: 65-80.
    5. Khazdair MR, Boskabady MH, Hosseini M, et al. The effects of Crocus sativus (saffron) and its constituents on nervous system: A review. Avicenna J Phytomed 2015; 5(5): 376-391.
    6. Khorasany AR, Hosseinzadeh H. Therapeutic effects of saffron (Crocus sativus L.) in digestive disorders: A review. Iran J Basic Med Sci 2016; 19(5): 455-469.
    7. Ungaro R, Mehandru S, Allen PB, et al. Ulcerative colitis. Lancet 2017; 389(10080): 1756-1770.
    8. Dulai PS, Jairath V. Acute severe ulcerative colitis: Latest evidence and therapeutic implications. Ther Adv Chronic Dis 2018; 9(2):65-72.
    9. Hindryckx P, Jairath V, D'Haens G. Acute severe ulcerative colitis: From pathophysiology to clinical management. Nat Rev Gastroenterol Hepatol 2016; 13(11): 654-664.
    10. Panés J, Alfaro I. New treatment strategies for ulcerative colitis. Expert Rev Clin Immunol 2017; 13(10): 963-973.
    11. Santana MT, Cercato LM, Oliveira JP, et al. Medicinal plants in the treatment of colitis: evidence from preclinical studies. Planta Med 2017; 83(7): 588-614.
    12. Wan P, Chen H, Guo Y, et al. Advances in treatment of ulcerative colitis with herbs: from bench to bedside. World J Gastroenterol 2014; 20(39): 14099-14104.
    13. Valatas V, Bamias G, Kolios G. Experimental colitis models: insights into the pathogenesis of inflammatory bowel disease and translational issues. Eur J Pharmacol 2015; 759: 253-264.
    14. Randhawa PK, Singh K, Singh N, et al. A review on chemical-induced inflammatory bowel disease models in rodents. Korean J Physiol Pharmacol 2014; 18(4): 279-288.
    15. Kawabata K, Tung NH, Shoyama Y, et al. Dietary crocin inhibits colitis and colitis-associated colorectal carcino-genesis in male ICR mice. Evid Based Complement Alternat Med 2012; doi: 10.1155/2012/820415.
    16. Ye B, van Langenberg DR. Mesalazine preparations for the treatment of ulcerative colitis: Are all created equal? World J Gastrointest Pharmacol Ther 2015; 6(4): 137-144.
    17. Li C, Lun W, Zhao X, et al. Allicin alleviates inflammation of trinitrobenzenesulfonic acid-induced rats and suppresses P38 and JNK pathways in Caco-2 cells. Mediators Inflamm 2015; 434692. doi: 10.1155 /2015/434692.
    18. Ancha HR, Kurella RR, McKimmey CC, et al. Effects of N-acetylcysteine plus mesalamine on prostaglandin synthesis and nitric oxide generation in TNBS-induced colitis in rats. Dig Dis Sci 2009; 54(4): 758-766.
    19. Cao PC, Xiao WX, Yan YB, et al. Preventive effect of crocin on osteoporosis in an ovariectomized rat model. Evid Based Complement Alternat Med 2014; doi:10.1155/2014/825181.
    20. Al-Rejaie SS, Abuohashish HM, Al-Enazi MM, et al. Protective effect of naringenin on acetic acid-induced ulcerative colitis in rats. World J Gastroenterol 2013; 19(34): 5633-5644.
    21. Heidari B, Sajjadi SE, Minaiyan M. Effect of Coriandrum sativum hydroalcoholic extract and its essential oil on acetic acid-induced acute colitis in rats. Avicenna J Phytomed 2016; 6(2): 205-214.
    22.  Adedara IA, Ojuade TJD, Olabiyi BF, et al. Taurine ameliorates renal oxidative damage and thyroid dysfunction in rats chronically exposed to fluoride. Biol Trace Elem Res 2017; 175(2): 388-395.
    23. Najafi A, Motaghi E, Hosseini MJ, et al. The effect of sodium valproate on acetic acid-induced colitis in rats. Inflammopharmacology 2017; 25(1): 137-145.
    24. Ghasemi-Pirbaluti M, Motaghi E, Najafi A, et al. The effect of theophylline on acetic acid induced ulcerative colitis in rats. Biomed Pharmacother 2017; 90: 153-159.
    25. Hosseinzadeh H, Sadeghnia HR. Safranal, a constituent of Crocus sativus (saffron), attenuated cerebral ischemia induced oxidative damage in rat hippocampus. J Pharm Pharm Sci 2005; 8(3): 394-399.
    26. Gassul MA. Nutrition and inflammatory bowel disease: Its relation to pathophysiology, outcome and therapy. Dig Dis 2003; 21(3): 220-227.
    27. Maloy KJ, Powrie F. Intestinal homeostasis and its breakdown in inflammatory bowel disease. Nature 2011; 474(7351): 298-306.
    28. Shalkami AS, Hassan M, Bakr AG. Anti-inflammatory, antioxidant and anti-apoptotic activity of diosmin in acetic acid-induced ulcerative colitis. Hum Exp Toxicol 2018; 37(1): 78-86.
    29. Ali AA, Abd A Haleem EN, Khaleel SA, et al. Protective effect of cardamonin against acetic acid-induced ulcerative colitis in rats. Pharmacol Rep 2017; 69(2): 268-275.
    30. Suluvoy JK, Sakthivel KM, Guruvayoorappan C, et al. Protective effect of Averrhoa bilimbi L. fruit extract on ulcerative colitis in Wistar rats via regulation of inflammatory mediators and cytokines. Biomed Pharmacother 2017; 91: 1113-1121.
    31. Jena G, Trivedi PP, Sandala B. Oxidative stress in ulcerative colitis: An old concept but a new concern. Free Radic Res 2012; 46(11): 1339-1345.
    32. Soufli I, Toumi R, Rafa H, et al. Overview of cytokines and nitric oxide involvement in immuno-pathogenesis of inflammatory bowel diseases. World J Gastrointest Pharmacol Ther 2016; 7(3): 353-360.
    33. Kazi HA, Qian Z. Crocetin reduces TNBS-induced experimental colitis in mice by downregulation of NFkB. Saudi J Gastroenterol 2009; 15(3):181-187.
    34. El-Maraghy SA, Rizk SM, Shahin NN. Gastroprotective effect of crocin in ethanol-induced gastric injury in rats. Chem Biol Interact 2015; 229: 26-35.
    35. Allgayer H. Review article: Mechanisms of action of mesalazine in preventing colorectal carcinoma in inflammatory bowel disease. Aliment Pharmacol Ther 2003; 18 (Suppl 2): 10-14.
    36. Ahmad H, Verma S, Kumar VL. Effect of roxithromycin on mucosal damage, oxidative stress and pro-inflammatory markers in experimental model of colitis. Inflamm Res 2018; 67(2): 147-155.
    37. Balaha M, Kandeel S, Elwan W. Garlic oil inhibits dextran sodium sulfate-induced ulcerative colitis in rats. Life Sci 2016; 146: 40-51.
    38. Lang A, Salomon N, Wu JC, et al. Curcumin in combination with mesalamine induces remission in patients with mild-to-moderate ulcerative colitis in a randomized controlled trial. Clin Gastroenterol Hepatol 2015; 13(8): 1444-1449.