POTENTIAL MODULATION OF DISEASE ACTIVITY INDICES AND INFLAMMATORY BIOMARKERS IN PATIENTS WITH ACTIVE INFLAMMATORY BOWEL DISEASE ON MELATONIN ADJUVANT THERAPY
DOI:
https://doi.org/10.22159/ajpcr.2018.v11i6.25218Keywords:
Inflammatory bowel disease, Oral melatonin, Disease activity indices, Matrix metalloproteinases, Erythrocyte sedimentation rateAbstract
 Objective: The objective of this study was to explore the benefits of melatonin supplementation in the active stage of moderate to severe inflammatory bowel diseases (IBDs) as an adjuvant to the standard immunosuppressant and biological targeting therapy in both Crohn's disease (CD) and ulcerative colitis (UC) patients.
Methods: This is an interventional prospective randomized controlled, open-label, single-center study was carried out on 50 patients visiting the biological unite diagnosed as moderate-severe active IBD. Melatonin adjuvant was added to the standard treatment.Â
 Results: Disease activity indices showed significant improvement in both diseases after melatonin adjuvant therapy compared to the standard treatment alone (CD −61.80 vs. 36.48%), (UC −74.48% vs. −46.66%) (p<0.01). The erythrocyte sedimentation rate (ESR) level showed higher percent of reduction after melatonin adjuvant in both diseases (p<0.05). CD patients presented with slight reduction in matrix metalloproteinases-9 (MMP-9) level following on melatonin adjuvant therapy compared to standard therapy (p˃0.05). At baseline, a significant correlation between severity scores of both diseases and both ESR and MMP-9 in UC patients, but after treatment, only the ESR level was correlated to the improvement in disease score in CD patients.
Conclusion: Melatonin produced marked improvement in the disease activity status in both CD and UC after receiving melatonin adjuvant in active stage of disease, and notable modulation of inflammatory biomarkers with no clear role on MMP-9 expression.
Downloads
References
Mozaffari S, Abdollahi M. Melatonin, a promising supplement in inflammatory bowel disease: A comprehensive review of evidences. Curr Pharm Design 2011;17:4372-8.
Saniabadi AR, Tanaka T, Ohmori T, Sawada K, Yamamoto T, Hanai H. Treating inflammatory bowel disease by adsorptive leucocytapheresis: A desire to treat without drugs. World J Gastroenterol 2014;20:9699- 715.
Jena G, Trivedi PP. A review of the use of melatonin in ulcerative colitis: Experimental evidence and new approaches. Inflamm Bowel Dis 2014;20:553-63.
Bubenik GA. Thirty four years since the discovery of gastrointestinal melatonin. J Physiol Pharm 2008;59 Suppl 2:33-51.
Jockers R, Maurice P, Boutin JA, Delagrange P. Melatonin receptors, heterodimerization, signal transduction and binding sites: what’s new? Br J Pharm 2008;154:1182-95.
Chen CQ, Fichna J, Bashashati M, Li YY, Storr M. Distribution, function and physiological role of melatonin in the lower gut. World J Gastroenterol 2011;17:3888-98.
Carrillo-Vico A, Lardone PJ, Ãlvarez-Sánchez N, RodrÃguez-RodrÃguez A, Guerrero JM. Melatonin: Buffering the immune system. Int J Mol Sci 2013;14:8638-83.
Ravishankar GA, Ramakrishna A. Serotonin and melatonin: Their functional role in plants. Food, Phytomedicine, and Human Health. Boca Raton: CRC Press; 2016.
Tahan G, Gramignoli R, Marongiu F, Aktolga S, Cetinkaya A, Tahan V, et al. Melatonin expresses powerful anti-inflammatory and antioxidant activities resulting in complete improvement of acetic-acid-induced colitis in rats. Dig Dis Sci 2011;56:715-20.
Kandil TS, Mousa AA, El-Gendy AA, Abbas AM. The potential therapeutic effect of melatonin in gastro-esophageal reflux disease. BMC Gastroenterol 2010;10:7.
Celinski K, Konturek PC, Konturek SJ, Slomka M, Cichoz-Lach H, Brzozowski T, et al. Effects of melatonin and tryptophan on healing of gastric and duodenal ulcers with Helicobacter pylori infection in humans. J Physiol Pharm 2011;62:521-6.
Abbas SH, Abdulridha MK, Najeb AA. Potential benefit of curcumin adjuvant therapy to the standard Helicobacter pylori eradication therapy in patients with peptic ulcer disease. Asian J Pharm Clin Res 2017;10:313-7.
Gopinathan S, Rameela N. Anti-ulcer activity of Aloe vera juice and Aloe vera and amla fruit combined juice in ethanol induced ulcerated rats. Int J Pharm Pharm Sci 2014;6:190-7.
Siah KT, Wong RK, Ho KY. Melatonin for the treatment of irritable bowel syndrome. World J Gastroenterol 2014;20:2492-8.
Carrillo-Vico A, Guerrero JM, Lardone PJ, Reiter RJ. A review of the multiple actions of melatonin on the immune system. Endocrine 2005;27:189-200.
Klupinska G, Wisniewska-Jarosinska M, Harasiuk A, Chojnacki C, Stec-Michalska K, Blasiak J, et al. Nocturnal secretion of melatonin in patients with upper digestive tract disorders. J Physiol Pharmacol 2006;57 Suppl 5:41-50.
Harbord M, Eliakim R, Bettenworth D, Karmiris K, Katsanos K, Kopylov U, et al. Third European evidence-based consensus on diagnosis and management of ulcerative Colitis. Part 2: Current management. J Crohn’s Colitis 2017;2017:1-24.
Gomollón F, Dignass A, Annese V, Tilg H, Van Assche G, Lindsay JO, et al. 3rd European evidence-based consensus on the diagnosis and management of Crohn’s disease 2016: Part 1: Diagnosis and medical management. J Crohn’s Colitis 2017;11:3-25.
Peyrin-Biroulet L, Panés J, Sandborn WJ, Vermeire S, Danese S, Feagan BG, et al. Defining disease severity in inflammatory bowel diseases: Current and future directions. Clin Gastroenterol Hepatol 2016;14:348-54.
National Clinical Guideline C. National Institute for Health and Clinical Excellence: Guidance. Ulcerative Colitis: Management in Adults, Children and Young People. London: Royal College of Physicians (UK); National Clinical Guideline Centre; 2013.
Walsh AJ, Bryant RV, Travis SP. Current best practice for disease activity assessment in IBD. Nat Rev Gastroenterol Hepatol 2016;13:567-79.
Firestein GS, Budd RC, Gabriel SE, McInnes IB, O’Dell JR. Acute Phase Reactants and the Concept of Inflammation. Kelley’s Textbook of Rheumatology. 9th ed. Ch 57. Philadelphia, PA: Elsevier Saunders; 2013. p. 818-29.
Human MMP-9 (Matrix Metalloproteinase 9) ELISA Kit. (Catalog No: E-EL-H1451). 8th ed. China: Elabscience Biotechnology; 2016. Available from: http://www.elabscience.com/index.php/product/view/aid/704.jsp. [Last updated on Aug 2016; Last cited on 2017 Jul 02].
Rakhimova O. Use of melatonin in combined treatment for inflammatory bowel diseases. Ter Arkh 2010;82:64-8.
Chojnacki C, Wisniewska-Jarosinska M, Walecka-Kapica E, Klupinska G, Jaworek J, Chojnacki J. Evaluation of melatonin effectiveness in the adjuvant treatment of ulcerative colitis. J Physiol Pharm 2011;62:327- 34.
Allen PB, Peyrin-Biroulet L. Moving towards disease modification in inflammatory bowel disease therapy. Curr Opin Gastroenterol 2013;29:397-404.
Gecse KB, Brandse JF, van Wilpe S, Lowenberg M, Ponsioen C, van den Brink G, et al. Impact of disease location on fecal calprotectin levels in Crohn’s disease. Scand J Gastroenterol 2015;50:841-7.
Bernstein CN, Wajda A, Svenson LW, MacKenzie A, Koehoorn M, Jackson M, et al. The epidemiology of inflammatory bowel disease in Canada: A population-based study. Am J Gastroenterol 2006;101:1559- 68.
Kappelman MD, Rifas-Shiman SL, Kleinman K, Ollendorf D, Bousvaros A, Grand RJ, et al. The prevalence and geographic distribution of crohn’s disease and ulcerative colitis in the united states. Clin Gastroenterol Hepatol 2007;5:1424-9.
Thia KT, Loftus EV Jr., Sandborn WJ, Yang SK. An update on the epidemiology of inflammatory bowel disease in asia. Am J Gastroenterol 2008;103:3167-82.
Halvani A, Mohsenpour F, Nasiriani K. Evaluation of exogenous melatonin administration in improvement of sleep quality in patients with chronic obstructive pulmonary disease. Tanaffos 2013;12:9-15.
Ranjbaran Z, Keefer L, Farhadi A, Stepanski E, Sedghi S, Keshavarzian A, et al. Impact of sleep disturbances in inflammatory bowel disease. J Gastroenterol Hepatol 2007;22:1748-53.
Zhang HM, Zhang Y. Melatonin: A well-documented antioxidant with conditional pro-oxidant actions. J Pineal Res 2014;57:131-46.
O’Sullivan S, Gilmer JF, Medina C. Matrix metalloproteinases in inflammatory bowel disease: An update. Mediators Inflamm 2015;2015:19.
Heljasvaara R, Nyberg P, Luostarinen J, Parikka M, Heikkilä P, Rehn M, et al. Generation of biologically active endostatin fragments from human collagen XVIII by distinct matrix metalloproteases. Exp Cell Res 2005;307:292-304.
Deng X, Tolstanova G, Khomenko T, Chen L, Tarnawski A, Szabo S, et al. Mesalamine restores angiogenic balance in experimental ulcerative colitis by reducing expression of endostatin and angiostatin: Novel molecular mechanism for therapeutic action of mesalamine. J Pharmacol Exp Ther 2009;331:1071-8.
Lee S, Jilani SM, Nikolova GV, Carpizo D, Iruela-Arispe ML. Processing of VEGF-A by matrix metalloproteinases regulates bioavailability and vascular patterning in tumors. J Cell Biol 2005;169:681-91.
Pope JL, Bhat AA, Sharma A, Ahmad R, Krishnan M, Washington MK, et al. Claudin-1 regulates intestinal epithelial homeostasis through the modulation of notch-signalling. Gut 2014;63:622-34.
Bailey JR, Bland PW, Tarlton JF, Peters I, Moorghen M, Sylvester PA, et al. IL-13 promotes collagen accumulation in Crohn’s disease fibrosis by down-regulation of fibroblast MMP synthesis: A role for innate lymphoid cells? PLoS One 2012;7:e52332.
Forrest CM, Mackay GM, Stoy N, Stone TW, Darlington LG. Inflammatory status and kynurenine metabolism in rheumatoid arthritis treated with melatonin. Br J Clin Pharm 2007;64:517-26.
Esposito E, Mazzon E, Riccardi L, Caminiti R, Meli R, Cuzzocrea S. Matrix metalloproteinase-9 and metalloproteinase-2 activity and expression is reduced by melatonin during experimental colitis. J Pineal Res 2008;45:166-73.
Published
How to Cite
Issue
Section
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.
