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      Effect of Shogaol on the Expression of Intestinal Stem Cell Markers in Experimentally Induced Colitis in BALB/c Mice

      research-article
      1 , , 1 , 2
      Analytical Cellular Pathology (Amsterdam)
      Hindawi

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          Abstract

          Aim

          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.

          Material & Methods

          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.

          Results

          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.

          Conclusion

          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.

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          Most cited references25

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          Activated macrophages are an adaptive element of the colonic epithelial progenitor niche necessary for regenerative responses to injury.

          We have identified cellular and molecular features of the stem cell niche required for marked amplification of mouse colonic epithelial progenitors (ColEPs) that occurs in response to wounding of the epithelium with dextran sodium sulfate. This regenerative response in areas adjacent to breaches in the epithelial barrier depends on the gut microbiota because ColEP proliferation is markedly diminished in germ-free animals. Analysis of conventionally raised C57BL/6 (B6) knockout mice lacking the Toll-like receptor signal transduction pathway component Myd88 and wild-type animals transplanted with Myd88(-/-) bone marrow, revealed that Myd88-mediated signaling through mesenchymal cells is also required for the ColEP response. Studies of B6 Csf1(op/op) (lacking macrophages) mice, Rag1(-/-) mice, and wild-type mice treated with neutrophil-specific Gr1 mAbs, disclosed that macrophages but not lymphocytes or neutrophils are necessary. GeneChip analysis of laser-capture-microdissected mesenchymal cells coupled with immunohistochemical and electron microscopic studies showed that, during the regenerative response, macrophages in the pericryptal stem cell niche express genes associated with their activation and extend processes to directly contact ColEPs near the crypt base. GeneChip analysis also identified a number of potential molecular mediators of regeneration expressed in the pericryptal progenitor niche, including secreted factors that stimulate epithelial proliferation and proteins involved in extracellular matrix and basement membrane function, stability, and growth factor binding. Together, these studies indicate that the colonic epithelial progenitor niche is a dynamic structure in which macrophages function as mobile "cellular transceivers" that coordinate inputs from luminal microbes and injured epithelium and transmit regenerative signals to neighboring ColEPs.
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            CD34+ mesenchymal cells are a major component of the intestinal stem cells niche at homeostasis and after injury.

            The intestinal epithelium is continuously renewed by intestinal epithelial stem cells (IESCs) positioned at the base of each crypt. Mesenchymal-derived factors are essential to maintain IESCs; however, the cellular composition and development of such mesenchymal niche remains unclear. Here, we identify pericryptal CD34(+) Gp38(+) αSMA(-) mesenchymal cells closely associated with Lgr5(+) IESCs. We demonstrate that CD34(+) Gp38(+) cells are the major intestinal producers of the niche factors Wnt2b, Gremlin1, and R-spondin1, and are sufficient to promote maintenance of Lgr5(+) IESCs in intestinal organoids, an effect mainly mediated by Gremlin1. CD34(+) Gp38(+) cells develop after birth in the intestinal submucosa and expand around the crypts during the third week of life in mice, independently of the microbiota. We further show that pericryptal CD34(+)gp38(+) cells are rapidly activated by intestinal injury, up-regulating niche factors Gremlin1 and R-spondin1 as well as chemokines, proinflammatory cytokines, and growth factors with key roles in gut immunity and tissue repair, including IL-7, Ccl2, Ptgs2, and Amphiregulin. Our results indicate that CD34(+) Gp38(+) mesenchymal cells are programmed to develop in the intestine after birth to constitute a specialized microenvironment that maintains IESCs at homeostasis and contribute to intestinal inflammation and repair after injury.
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              Zingiberis rhizoma: a comprehensive review on the ginger effect and efficacy profiles.

              Zingiberis rhizoma is used as a broadspectrum antiemetic. We, therefore, conducted a comprehensive review of the literature to summarize the pharmacological and clinical effects of this popular plant material. Although clinical and experimental studies suggest that ginger has some antiemetic properties, clinical evidence beyond doubt is only available for pregnancy-related nausea and vomiting. Meta-analyses could not demonstrate the postoperative antiemetic effectiveness, and effect in motion sickness or nausea/vomiting of other ethiology. It also remains to be confirmed that proprietary ginger preparations are clinically useful to alleviate osteoarthritic or other pain, although there is no doubt that ginger constituents interfere with the inflammatory cascade and the vanilloid nociceptor. Ginger exerts in vitro antioxidative, antitumorigenic and immunomodulatory effects and is an effective antimicrobial and antiviral agent. Animal studies demonstrate effects on the gastrointestinal tract, the cardiovascular system, on experimental pain and fever, antioxidative, antilipidemic and antitumor effects, as well as central and other effects. The most relevant human pharmacological studies require a confirmatory study to exclude interaction of ginger preparations with platelet aggregation. Pharmacokinetic data are only available for [6]-gingerol and zingiberene. Preclinical safety data do not rule out potential toxicity, which should be monitored especially following ginger consumption over longer periods.
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                Author and article information

                Contributors
                Journal
                Anal Cell Pathol (Amst)
                Anal Cell Pathol (Amst)
                ACP
                Analytical Cellular Pathology (Amsterdam)
                Hindawi
                2210-7177
                2210-7185
                2019
                6 March 2019
                : 2019
                : 5134156
                Affiliations
                1Department of Anatomy and Pathology, College of Veterinary Medicine, University of Sulaimani, Kurdistan, Iraq
                2Department of Medical Laboratory Sciences, Komar University of Science and Technology, Kurdistan Region, Iraq
                Author notes

                Academic Editor: Consuelo Amantini

                Author information
                http://orcid.org/0000-0002-1751-0360
                http://orcid.org/0000-0001-9568-4596
                Article
                10.1155/2019/5134156
                6431407
                29eca223-c649-432b-a02e-85e482a5fc70
                Copyright © 2019 Snur M. A. Hassan and Ali Hussein Hassan.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 23 June 2018
                : 6 January 2019
                Funding
                Funded by: University of Sulaimani
                Funded by: College of Veterinary Medicine
                Categories
                Research Article

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