Date Published: March 6, 2019
Author(s): Snur M. A. Hassan, Ali Hussein Hassan.
This study is aimed at investigating the effect of Shogaol, a phenolic constituent of ginger, on dextran sodium sulfate- (DSS-) induced ulcerative colitis (UC) in mice in comparison with 6-thioguanine (6-TG), an immune-suppressant chemotherapeutic medicine used for treatment of ulcerative colitis.
Thirty-six adult, male and female BALB/c mice were randomly divided into six groups: group 1 (control negative) not exposed to DSS and did not receive any treatment, group 2 (control positive) exposed to DSS but did not receive any treatment, group 3 exposed to DSS and treated by 0.1 mg/kg of 6-thioguanine, and groups 4, 5, and 6 exposed to DSS and treated by 10, 20, and 40 mg/kg b.w. Shogaol, respectively. At day 56, the mice were checked for their disease activity index (DAI) and they were sacrificed. The colons of the mice were examined for length measurement, histological index score, and the expression of CD133 and CD34 stem cell markers.
Shogaol showed a better curative effect than did 6-TG in repairing the colonic mucosal damages in DSS-exposed mice as indicated by the levels of CD133 and CD34 expression in the colonic crypts and by the DAI score, colon length measurements, & histological index score which were significantly reduced in mice treated by Shogaol, particularly the 20 and 40 mg/kg BW doses.
The results of this study indicated that oral treatment with the ginger-derived substance Shogaol could be better than the conventional immunosuppressive chemotherapeutic remedy 6-TG in treatment of DSS-induced UC.
Ulcerative colitis is a chronic inflammatory disease of the colon and rectum characterized by bloody diarrhea, intestinal mucosal ulceration, and infiltration of neutrophils and lymphocytes within the mucosal layer [1, 2]. Multiple causes such as environmental changes, gene variations, and gut microbes were supposed to be associated with UC etiology [3, 4]. DSS-induced colitis, a form of UC model in terms of morphological and pathophysiological features [5, 6], has been generally used experimentally to evaluate the therapeutic effects and to realize the molecular basis of action of new compounds to be used for the treatment of UC [5, 7].
As an inflammatory bowel disease (IBD), ulcerative colitis is regarded as an important and increasing health care crisis worldwide, and the precise etiology remains unknown . However, intestinal regeneration plays an important role in the healing of the intestinal mucosa . In comparison with mice of the control negative group, the control positive mice showed severe signs of ulcerative colitis (as indicated by DAI parameters including bloody stool, diarrhea, and rectal bleeding) associated with colon shortening and marked histopathological lesions in the colon represented by mucosal damages (focal erosion or ulceration) and mucosal-submucosal or transmural infiltration of inflammatory cells. These results are in agreement with some related findings [30, 31] which reported that DSS-induced UC in the murine model causes adverse colonic abnormalities associated with bloody stool, diarrhea, and rectal bleeding.
The results of the current study indicated that oral treatment by the ginger-derived substance Shogaol, particularly the 20 and 40 mg/kg b.w. doses, could be better than the conventional immunosuppressive chemotherapeutic remedy 6-TG in the treatment of DSS-induced UC because treatment by the latter compound is usually associated with unfavorable side effects such as hepatotoxicity, nephrotoxicity, and bone marrow suppression. The DAI parameters (bloody stool, diarrhea, and rectal bleeding), colon measurements, and histopathological index scores revealed a better positive effect of Shogaol in improvement of colitis due to its anti-inflammatory effect than 6-TG, and the IHC analysis also revealed a better effect for Shogaol than 6-TG in activation of CD133 which has a significant role in intestinal regeneration and in regulating intestinal homeostasis. In addition, the IHC results showed a better effective role of Shogaol than 6-TG in the activation of CD34 which plays an important role in improving crypt damages through the activation of mesenchymal cells which represent a major component of the intestinal stem cell niche in homeostasis and after injury.