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      Effects of ondansetron and [6]-gingerol on pica and gut microbiota in rats treated with cisplatin

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          Abstract

          Purpose

          [6]-gingerol is one of the main components of ginger with many biological activities. In this study, the effects of ondansetron and [6]-gingerol on pica and gut microbiota in rats injected with cisplatin were evaluated.

          Materials and methods

          Rat model of cisplatin-induced pica was established, and the effects of ondansetron and [6]-gingerol on the gut microbiota were further studied by 16S rDNA gene analysis.

          Results

          The results showed that the total intake of kaolin of the rats injected with cisplatin was significantly increased, and treatment of ondansetron and [6]-gingerol in advance could significantly ameliorate the pica induced by cisplatin. The body weight of the rats injected with cisplatin was decreased compared with the control group. The 16S rDNA gene analysis has shown that ondansetron, [6]-gingerol and cisplatin could increase the relative abundance of Bacteroidetes and decrease Firmicutes on phylum level.

          Conclusion

          [6]-gingerol was as effective as ondansetron in the treatment of pica induced by cisplatin in rats, and it seemed that [6]-gingerol had the potential to ameliorate the alteration of gut microbiome, but it needs further study.

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          Most cited references 22

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          Berberine, an Epiphany Against Cancer

          Alkaloids are used in traditional medicine for the treatment of many diseases. These compounds are synthesized in plants as secondary metabolites and have multiple effects on cellular metabolism. Among plant derivatives with biological properties, the isoquinoline quaternary alkaloid berberine possesses a broad range of therapeutic uses against several diseases. In recent years, berberine has been reported to inhibit cell proliferation and to be cytotoxic towards cancer cells. Based on this evidence, many derivatives have been synthesized to improve berberine efficiency and selectivity; the results so far obtained on human cancer cell lines support the idea that they could be promising agents for cancer treatment. The main properties of berberine and derivatives will be illustrated.
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            Well-balanced commensal microbiota contributes to anti-cancer response in a lung cancer mouse model.

            The intestinal microflora affects inflammation and immunity, not only locally at the mucosal level but also systemically, raising the question of whether the microflora affects inflammatory processes that contribute to cancer and its therapy. Prebiotics have also been found to play an antitumor role that is not limited to the gut. We investigated the antitumor roles of the intestinal microbiota using the Lewis lung cancer mouse model. In mice treated with cisplatin combined with ABX (an antibiotic cocktail of vancomycin, ampicillin, and neomycin), which can destroy the host commensal microflora, the tumor size was larger than in mice on a single treatment of cisplatin. Moreover, the survival rate of mice treated with cisplatin combined with ABX was significantly reduced. In contrast, mice treated with cisplatin combined with Lactobacillus bacteria had smaller tumors and an improved survival rate. Further study on gene expression indicated that ABX can partially impair the function of cisplatin by upregulating the expression of VEGFA and downregulating the expression of BAX and CDKN1B. The expression of IFN-γ, GZMB, and PRF1 in the CD8(+) T cells of these mice was reduced by ABX, indicating an immuno-enhancement role of commensal microbiota. Conversely, Lactobacillus co-treatment mice showed an enhanced antitumor response with upregulated IFN-γ, GZMB, and PRF1 expression. We conclude that the commensal microbiota contributes to the anti-lung cancer response and probiotics co-treatment can enhance the antigrowth and proapoptotic effects of cisplatin.
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              Zingiber officinale (ginger) as an anti-emetic in cancer chemotherapy: a review.

              Despite significant advances and development of novel anti-emetics, nausea and vomiting (emesis) is a major side-effect of cancer chemotherapy. At times, severe nausea and vomiting may also lead to reduction in adherence to the treatment regimen, and this will concomitantly affect the patient's survival. The rhizome of Zingiber officinale, commonly known as ginger, is globally an important spice. It has been used for centuries in the Indian, Chinese, Arabic, Tibetan, Unani, and Siddha systems of traditional medicine to treat nausea and vomiting induced by different stimuli. Preclinical studies with experimental animals (dogs and rats) have shown that the various extracts of ginger and the ginger juice possess anti-emetic effects against chemotherapy-induced nausea and vomiting. Gingerol, the active principle, is also shown to possess anti-emetic effects in minks. However, with regard to humans, while most studies have been supportive of the preclinical observations, a few have been contradictory. The exact mechanism responsible for the anti-emetic effects of ginger is unknown; however, the ginger phytochemicals, especially 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol, may function as a 5-hydroxytryptamine (5-HT3) antagonist, NK1 antagonist, antihistaminic, and possess prokinetic effects. The present review for the first time attempts to address the anti-emetic observations and the variability in response of the anti-emetic effects of ginger in cancer chemotherapy. An attempt is also made to address the lacunae in the published studies and emphasize aspects that need further investigations for ginger to be of use in clinics as an anti-emetic agent in the future.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                DDDT
                dddt
                Drug Design, Development and Therapy
                Dove
                1177-8881
                01 August 2019
                2019
                : 13
                : 2633-2641
                Affiliations
                [1 ]School of Chinese Materia Medica, Guangdong Pharmaceutical University , Guangzhou 510006, People’s Republic of China
                [2 ]School of Chinese Medicine, Shandong University of Traditional Chinese Medicine , Jinan 250355, People’s Republic of China
                [3 ]The First Affiliated Hospital (School of Clinical Medicine), Guangdong Pharmaceutical University , Guangzhou 510080, People’s Republic of China
                Author notes
                Correspondence: Yanhong YangThe First Affiliated Hospital (School of Clinical Medicine), Guangdong Pharmaceutical University , Nong-Lin-Xia Road 19#, Yue-Xiu District, Guangzhou510080, People’s Republic of ChinaTel +86 203 935 3115Fax +86 203 935 2606Email 1764941457@ 123456qq.com
                Ke NieSchool of Chinese Materia Medica, Guangdong Pharmaceutical University , 280 Waihuan East Road, Panyu District, Guangzhou510006, People’s Republic of ChinaTel +86 203 935 2557Email nicknk@ 123456hotmail.com
                [*]

                These authors contributed equally to this work

                Article
                211845
                10.2147/DDDT.S211845
                6682320
                © 2019 Feng et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                Page count
                Figures: 3, Tables: 3, References: 28, Pages: 9
                Categories
                Original Research

                Pharmacology & Pharmaceutical medicine

                gut microbiota, cisplatin, kaolin, pica, [6]-gingerol, ondansetron

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