Abstract
Ulcerative colitis (UC) is a chronic inflammatory bowel disease that affects the mucosa and submucosa of colon. The pathogenesis of ulcerative colitis (UC) is related to reduced antioxidant capacity and increased inflammatory processes. Reactive oxygen metabolites are the potent inflammatory mediators that may be involved in tissue injury in inflammatory bowel disease. Conventional drug therapies for UC come with a myriad of side effects which further raise the need for natural bioactive agents. Curcumin has proven to be beneficial in the prevention and treatment of a number of inflammatory diseases, but due its poor bioavailability, the therapeutic applications are limited. Thus, to enhance its bioavailability, a new formulation - curcumin-galactomannoside (CGM)- was made by complexing curcumin with galactomannans derived from fenugreek. The present study aims to evaluate the effects of CGM on experimental UC model. Adult male Wistar rats were divided into 5 groups: normal control rats (NC); ulcerative colitis control rats (UC); UC + sulfasalazine (SS) treated; UC + curcumin (CM) treated; and UC + CGM supplemented for 21 days. The colonic mucosal injury was assessed by macroscopic and histological examination, along with evaluation of antioxidant status, inflammatory mediators, and gene expressions. Administration of CGM significantly enhanced antioxidant activities and decreased the level of inflammatory mediators and also suppressed the expression of inflammatory markers as compared with other groups. In conclusion, findings from these results reveal that CGM exerts marked curative effects on acute experimental colitis, possibly by regulating the antioxidant status and modulating inflammatory cascade.
Similar content being viewed by others
References
Aleisa, A.M., S.S. Al-Rejaie, H.M. Abuohashish, M.S. Ola, M.Y. Parmar, and M.M. Ahmed. 2014. Pretreatment of Gymnema sylvestre revealed the protection against acetic acid-induced ulcerative colitis in rats. BMC Complement Altern Med 14: 1–11.
Benke, G.M., and S.D. Murphy. 1974. Effect of TOTP pretreatment on paraoxon and methyl paraoxon detoxification in rats. Res Commun Chem Pathol Pharmacol 8: 665–672.
Bjerrum, O.W., M.H. Nissen, and N. Borregaard. 1990. Neutrophil beta-2 microglobulin: An inflammatory mediator. Scand J Immunol 32: 233–242.
Boots, A.W., G.R. Haenen, and A. Bast. 2008. Health effects of quercetin: From antioxidant to nutraceutical. Eur J Pharmacol 585: 325–337.
Brian, K.R., A. Samuel, B. Andre, A.S. Keith, and L.W. John. 1996. Exacerbation of inflammation-associated colonic injury in rat through inhibition of cyclooxygenase-2. J Clin Invest 98: 2076–2085.
Cooper TH, Clark G, Guzinski J (1994) Teas, spices and herbs, In: Food phytochemicals, (eds) American Chemical Society.,Washington DC. 231–236.
Das, I. 1985. Raised C-reactive protein levels in serum from smokers. Clin Chim Acta 153: 9–13.
Debnath, T., D.H. Kim, and B.O. Lim. 2013. Natural products as a source of anti-inflammatory agents associated with inflammatory bowel disease. Molecules 18: 7253–7270.
Droge, W. 2002. Free radicals in the physiological control of cell function. Physiol Rev 82: 47–95.
El-Abhar, H.S., L.N. Hammad, and H.S. Gawad. 2008. Modulating effect of ginger extract on rats with ulcerative colitis. J Ethnopharmacol 118: 367–372.
Engvall, E., and P. Perlman. 1971. Enzyme linked immunosorbant assay (ELISA): Quantitiative assay of immunoglobulin G. Immunochemistry 8: 871–874.
Forstermann, U., and H. Kleinert. 1995. Nitric oxide synthase: Expression and expressional control of the three isoforms. Naunyn Schmiedeberg Arch Pharmacol 352: 351–364.
Gillum, R.F., D.D. Ingram, and D.M. Makuc. 1993. White blood cell count, coronary heart disease, and death: The NHANESI epidemiologic follow-up study. Am Heart J 125: 855–863.
Gonzalez, R., et al. 1999. Anti-inflammatory activity of phycocyanin extract in acetic acid-induced colitis in rats. Pharmacol Res 39: 55–59.
Grisham, M.B. 1994. Oxidants and free radicals in inflammatory bowel disease. Lancet 344: 859–861.
Halpin, S.J., and A.C. Ford. 2012. Prevalence of symptoms meeting criteria for irritable bowel syndrome in inflammatory bowel disease: Systemic review and meta-analysis. Am J Gasterology 107: 1474–1482.
Inoue, R., T. Yajima, and T. Tsukahara. 2017. Expression of TLR2 and TLR4 in murine small intestine during postnatal development. Biosci Biotechnol Biochem 81: 350–358.
Jian, Y.T., G.F. Mai, J.D. Wang, Y.L. Zhang, R.C. Luo, and Y.X. Fang. 2005. Preventive and therapeutic effects of NF-kappa B inhibitor curcumin in rats colitis induced by trinitrobenzene sulfonic acid. World J Gastroenterol 11: 1747–1752.
Kakkar, P., B. Das, and P.A. Viswanathan. 1984. Modified spectrophotometric assay of superoxide dismutase. Indian J Biochem Biophys 21: 130–132.
Kandori, H., K. Hirayama, M. Takeda, and K. Doi. 1996. Histochemical, lectin-histochemical and morphometrical characteristics of intestinal goblet cells of germ-free and conventional mice. Exp Anim 45: 155–160.
Krishnakumar, I.M., R. Abhilas, K. Dinesh, K. Ramadasan, and M. Balu. 2012. An enhanced bioavailable formulation of curcumin using fenugreek- derived soluble dietary fibre. J Funct Foods 4: 348–357.
Lawrence, R.A., and R.F. Burk. 1976. Glutathione peroxidase activity in selenium-deficient rat liver. Biochem Biophys Res Commun 7: 1952–1958.
Lowry, O.H., N.J. Rosebrough, A.L. Farr, and R.J. Randall. 1951. Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265–275.
Maehly, A.C., and B. Chance. 1954. The assay of catalases and peroxidases. Methods Biochem Anal 1: 357–424.
Masoodi, I., B.M. Tijjani, H. Wani, N.S. Hassan, A.B. Khan, and S. Hussain. 2011. Biomarkers in the management of ulcerative colitis: A brief review. Ger Med Sci 9: 1–7.
Mazlam, M.Z., and H.J. Hodgson. 1994. Why measure C reactive protein? Gut 35: 5–7.
McKernan, D.P., and D.P. Finn. 2014. An appealing new therapeutic for ulcerative colitis? Gut 63: 1207–1208.
Mehrabani, D., F. Bahrami, S.V. Hosseini, M.J. Ashraf, N. Tanideh, A. Rezaianzadeh, M. Amini, and A. Amini. 2012. The healing effect of Teucrium polium in acetic acid-induced ulcerative colitis in the dog as an animal model. Middle East J Dig Dis 4: 40–47.
Mousavizadeh, K., R. Rahimian, G. Fakhfouri, F.S. Aslani, and P. Ghafourifar. 2009. Anti-inflammatory effects of 5-HT receptor antagonist, tropisetron on experimental colitis in rats. Eur J Clin Investig 39: 375–383.
Nieto, N. 2000. Experimental ulcerative colitis impairs antioxidant defense system in rat intestine. Dig Dis Sci 45: 1820–1827.
Ohkawa, H., N. Ohishi, and K. Yagi. 1979. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95: 351–358.
Ordas, I., L. Eckmann, M. Talamini, D.C. Baumgart, and W.J. Sandborn. 2012. Ulcerative colitis. Lancet 380: 1606–1619.
Pfeiffer, C.J., and B.S. Qiu. 1995. Effects of chronic nitric oxide synthase inhibition on TNB-induced colitis in rats. J Pharm Pharmacol 47: 827–832.
Rezaie, A., R.D. Parker, and M. Abdollahi. 2007. Oxidative stress and pathogenesis of inflammatory bowel disease: An epiphenomenon or the cause? Dig Dis Sci 52: 2015–2021.
Rizvi, S., and N. Mishra. 2013. Traditional Indian medicines used for the management of diabetes mellitus. J Diabetes Res 2013: 1–11.
Sharma, S., J.D. Strutzman, G.J. Kellof, and V.E. Steele. 1994. Screening of potential chemopreventive agents using biochemical markers of carcinogenesis. Cancer Res 54: 5848–5855.
Shimizu, T., K. Kondo, and O. Hayaishi. 1981. Role of prostaglandin endoperoxides in the serum thiobarbituric acid reaction. Arch Biochem Biophys 206: 271–276.
Sivaprasad, R., M. Nagaraj, and P. Varalakshmi. 2004. Combined efficacies of lipoic acid and 2,3-dimercaptosuccinic acid against lead-induced lipid peroxidation in rat liver. J Nutr Biochem 15: 18–23.
Specian, R.D., and M.G. Oliver. 1991. Functional biology of intestinal goblet cells. Am J Phys 260: 183–193.
Stefano, M., M. Francesco, S. Paola, B. Marta, and R. Luca. 2017. Myeloperoxidase expression in human colonic mucosa is related to systemic oxidative balance in healthy subjects. Redox Rep 22: 399–407.
Verma, S., and E.T.H. Yeh. 2003. C-reactive protein and atherothrombosis—beyond a biomarker: An actual partaker of lesion formation. Am J Physiol Regul Integr Comp Physiol 285: 1253–1306.
Wallace, J.L., and B.C. Chin. 1997. Inflammatory mediators in gastrointestinal defense and injury. Proc Soc Exp Biol Med 214: 192–203.
Willcox, J.K., S.L. Ash, and G.L. Catignani. 2004. Antioxidants and prevention of chronic disease. Crit Rev Food Sci Nutr 44: 275–295.
Yasukawa, K., H. Tokuda, X. Tun, H. Utsumi, and K. Yamada. 2012. The detrimental effect of nitric oxide on tissue is associated with inflammatory events in the vascular endothelium and neutrophils in mice with dextran sodium sulfate-induced colitis. Free Radic Res 46: 1427–1436.
Acknowledgments
We express our sincere gratitude to Mr. Jayaram V, cytotechnician, for helping all the histopathological studies and M/s Akay Flavours & Aromatics Pvt. Ltd., Cochin, India, for the sample.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
The authors declare that they have no conflict of interest. CGM is the patented curcumin formulation of M/s Akay Flavours & Aromatics Pvt. Ltd., Cochin, India, trademarked as CurQfen®.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Sheethal, S., Ratheesh, M., Jose, S.P. et al. Anti-Ulcerative Effect of Curcumin-Galactomannoside Complex on Acetic Acid-Induced Experimental Model by Inhibiting Inflammation and Oxidative Stress. Inflammation 43, 1411–1422 (2020). https://doi.org/10.1007/s10753-020-01218-9
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10753-020-01218-9