The possibility of using shogaol for treatment of ulcerative colitis

Document Type : Original Article


Department of Anatomy and Pathology, College of Veterinary Medicine, Sulaimani University, Kurdistan, Iraq


Objective(s): This study aimed to investigate the effect of Shogaol on dextran sodium sulfate (DSS)- induced ulcerative colitis (UC) in mice compared to an immune-suppressant chemotherapeutic medicine, known as 6-thioguanine (6-TG).
Materials and Methods: Thirty-six adult BALB/c mice were divided into six groups: group 1 (positive control): no DSS exposure and no treatment; group 2 (negative control): DSS exposure without treatment; group 3 (vehicle control): DSS exposure and olive oil treatment; group 4: DSS exposure and 0.3 mg/kg 6-TG treatment; group 5: DSS exposure and 20 mg/kg Shogaol treatment; and group 6: DSS exposure and 40 mg/kg Shogaol treatment. At day 16, the mice were euthanized and UC was evaluated according to colon length, histologically index score and expression scores of the epidermal growth factor receptor (EGFR).
Results: The disease activity index (DAI) and histological index scores of mice treated with 40 mg/kg body weight (BW) Shogaol were approximately lower than the corresponding scores of mice treated with 6-TG. In addition, the rate of healing in the former mice was approximately 3 folds higher than that of the latter ones as indicated by the lack of EGFR expression in colonic glands and macrophages.
Conclusion: These findings showed that the therapeutic effect of 40 mg/kg BW Shogaol could be better than 6-TG in the treatment of UC, and it may draw the attention regarding the priority of using this cheap plant-derived substance for treatment of the inflammatory bowel diseases because treatment with 6-TG is usually associated with adverse side effects.


Main Subjects

1. Xavier R, Podolsky D. Unravelling the pathogenesis of inflammatory bowel disease. Nature 2007; 448:427-434.
2. Brant SR. Update on the heritability of inflammatory bowel disease: the importance of twin studies. Inflamm Bowel Dis 2011; 17:1-5.
3. Chassaing B, Darfeuille–Michaud A. The commensal microbiota and enteropathogens in the pathogenesis of inflammatory bowel diseases. Gastroenterology 2011; 140:1720-1728.
4. Riva G, Wiederhold B, Mantovani F, Gaggioli A. Interreality: the experiential use of technology in the treatment of obesity. Clin Pract Epidemiol Ment Health 2011; 7:51-61.
5. Okayasu I, Hatakeyama S, Yamada M, Ohkusa T, Inagaki Y, Nakaya R. A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology 1990; 98:694-702.
6. Toiyama Y, Mizoguchi A, Okugawa Y, Koike Y, Morimoto Y, Araki T, et al. Intravital imaging of DSS-induced cecal mucosal damage in GFP-transgenic mice using two-photon microscopy. J Gastroenterol 2010; 45:544-553.
7. Farombi EO, Adedara IA, Ajayi BO, Ayepola OR, Egbeme EE. Kolaviron, a natural antioxidant and anti‐inflammatory phytochemical prevents dextran sulphate sodium‐induced colitis in rats. Basic Clin Pharmacol Toxicol 2013; 113:49-55.
8. Bernstein CN. Treatment of IBD: where we are and where we are going. Am J Gastroenterol 2015; 110:114-126.
9. Neurath MF. Current and emerging therapeutic targets for IBD. Nat Rev Gastroenterol Hepatol 2017; 14:269-278.
10. Ok S, Jeong WS. Optimization of extraction conditions for the 6-shogaol-rich extract from ginger (Zingiber officinale Roscoe). Prev Nutr Food Sci 2012; 17:166-171.
11. Hu R, Zhou P, Peng YB, Xu X, Ma J, Liu Q, et al. 6-Shogaol induces apoptosis in human hepatocellular carcinoma cells and exhibits anti-tumor activity in vivo through endoplasmic reticulum stress. PloS One 2012; 7:e39664.
12. Cohen S, Carpenter G. Human epidermal growth factor: isolation and chemical and biological properties. Proc Natl Acad Sci USA 1975; 72:1317-1321.
13. Wright NA, Pike C, Elia G. Induction of a novel epidermal growth factor-secreting cell lineage by mucosal ulceration in human gastrointestinal stem cells. Nature 1990; 343:82-85.
14. Yarden Y. The EGFR family and its ligands in human cancer: signalling mechanisms and therapeutic opportunities. Eur J Cancer 2001; 37:3-8.
15. Kitajima S, Takuma S, Morimoto M. Histological analysis of murine colitis induced by dextran sulfate sodium of different molecular weights. Exp Anim 2000; 49:9-15.
16. Kverka M, Rossmann P, Tlaskalova-Hogenova H, Klimesova K, Jharap B, de Boer NK, et al. Safety and efficacy of the immunosuppressive agent 6-tioguanine in murine model of acute and chronic colitis. BMC Gastroenterol 2011; 11:47.
17. Alex P, Zachos NC, Nguyen T, Gonzales L, Chen TE, Conklin LS, et al. Distinct cytokine patterns identified from multiplex profiles of murine DSS and TNBS‐induced colitis. Inflamm Bowel Dis 2009; 15:341-352.
18. Erben U, Loddenkemper C, Doerfel K, Spieckermann S, Haller D, Heimesaat MM, et al. A guide to histomorphological evaluation of intestinal inflammation in mouse models. Int J Clin Exp Pathol 2014; 7:4557-4576.
19. Bourouba M, Benyelles-Boufennara A, Terki N, Baraka-Kerboua E, Bouzid K, Touil-Boukoffa C. Epidermal growth factor receptor (EGFR) abundance correlates with p53 and Bcl-2 accumulation and patient age in a small cohort of North African nasopharyngeal carcinoma patients. Eur Cytokine Netw 2011; 22:38-44.
20. Gu Y, Zhang S, Wu Q, Xu S, Cui Y, Yang Z, et al. Differential expression of decorin, EGFR and cyclin D1 during mammary gland carcinogenesis in TA2 mice with spontaneous breast cancer. J Exp Clin Cancer Res 2010; 29:6.
21. Qualls JE, Tuna H, Kaplan AM, Cohen DA. Suppression of experimental colitis in mice by CD11c+ dendritic cells. Inflamm Bowel Dis 2008; 15:236-247.
22. Cominelli F, Arseneau KO, Rodriguez-Palacios A, Pizarro TT. Uncovering Pathogenic Mechanisms of Inflammatory Bowel Disease Using Mouse Models of Crohn’s Disease–Like IIeitis: What is the Right Model?. Cell Mol Gastroenterol Hepatol 2017; 4:19-32.
23. Abu-Gharbieh E, Bayoumi FA, Ahmed NG. Alleviation of antioxidant defense system by ozonized olive oil in DNBS-induced colitis in rats. Mediators Inflamm 2014; 2014:967205.
24. Levy AS, Simon O, Shelly J, Gardener M. 6-Shogaol reduced chronic inflammatory response in the knees of rats treated with complete Freund’s adjuvant. BMC Pharmacol 2006; 6:12.
25. Zhang M, Xu C, Liu D, Han MK, Wang L, Merlin D. Oral delivery of nanoparticles loaded with ginger active compound, 6-shogaol, attenuates ulcerative colitis and promotes wound healing in a murine model of ulcerative colitis. J Crohn’s Colitis 2018; 12:217-229.
26. Dubé PE, Yan F, Punit S, Girish N, McElroy SJ, Washington MK, et al. Epidermal growth factor receptor inhibits colitis-associated cancer in mice. J Clin Invest 2012; 122:2780-2792.
27. Lu N, Wang L, Cao H, Liu L, Van Kaer L, Washington MK, et al. Activation of the epidermal growth factor receptor in macrophages regulates cytokine production and experimental colitis. J Immunol 2014; 192:1013-1023.
28. Gill RA, Onstad GR, Cardamone JM, Maneval DC, Sumner HW. Hepatic veno-occlusive disease caused by 6-thioguanine. Ann Intern Med 1982; 96:58-60.
29. Weiss RB, Poster DS. The renal toxicity of cancer chemotherapeutic agents. Cancer Treat Rev 1982; 9:37-56.