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      Studies of the effects and mechanisms of ginsenoside Re and Rk 3 on myelosuppression induced by cyclophosphamide

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          Abstract

          Background

          Ginsenoside Re (Re) is one of the major components of Panax ginseng Meyer. Ginsenoside Rk 3 (Rk 3) is a secondary metabolite of Re. The aim of this study was to investigate and compare the effects and underlying mechanisms of Re and Rk 3 on cyclophosphamide-induced myelosuppression.

          Methods

          The mice myelosuppression model was established by intraperitoneal (i.p.) injection of cyclophosphamide. Peripheral blood cells, bone marrow nucleated cells, and colony yield of hematopoietic progenitor cells in vitro were counted. The levels of erythropoietin, thrombopoietin, and granulocyte macrophage colony-stimulating factor in plasma were measured by enzyme-linked immunosorbent assay. Bone marrow cell cycle was performed by flow cytometry. The expression of apoptotic protein bcl-2, bax, and caspase-3 was detected by Western blotting.

          Results

          Both Re and Rk 3 could improve peripheral blood cells, bone marrow nucleated cell counts, thymus index, and spleen index. Furthermore, they could enhance the yield of colonies cultured in vitro and make the levels of granulocyte macrophage colony-stimulating factor, erythropoietin, and thrombopoietin normal, reduce the ratio of G 0/G 1 phase cells, and increase the proliferation index. Finally, Re and Rk 3 could upregulate the expression of bcl-2, whereas they could downregulate the expression of bax and caspase-3.

          Conclusion

          Re and Rk 3 could improve the hematopoietic function of myelosuppressed mice. The effect of Rk 3 was superior to that of Re at any dose. Regulating the levels of cytokines, promoting cells enter the normal cell cycle, regulating the balance of bcl-2/bax, and inhibiting the expression of caspase-3 may be the effects of Re and Rk 3 on myelosuppression.

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          Most cited references38

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          Cellular and molecular mechanisms of stress-induced premature senescence (SIPS) of human diploid fibroblasts and melanocytes.

          Replicative senescence of human diploid fibroblasts (HDFs) or melanocytes is caused by the exhaustion of their proliferative potential. Stress-induced premature senescence (SIPS) occurs after many different sublethal stresses including H(2)O(2), hyperoxia, or tert-butylhydroperoxide. Cells in replicative senescence share common features with cells in SIPS: morphology, senescence-associated beta-galactosidase activity, cell cycle regulation, gene expression and telomere shortening. Telomere shortening is attributed to the accumulation of DNA single-strand breaks induced by oxidative damage. SIPS could be a mechanism of accumulation of senescent-like cells in vivo. Melanocytes exposed to sublethal doses of UVB undergo SIPS. Melanocytes from dark- and light- skinned populations display differences in their cell cycle regulation. Delayed SIPS occurs in melanocytes from light-skinned populations since a reduced association of p16(Ink-4a) with CDK4 and reduced phosphorylation of the retinoblastoma protein are observed. The role of reactive oxygen species in melanocyte SIPS is unclear. Both replicative senescence and SIPS are dependent on two major pathways. One is triggered by DNA damage, telomere damage and/or shortening and involves the activation of the p53 and p21(waf-1) proteins. The second pathway results in the accumulation of p16(Ink-4a) with the MAP kinase signalling pathway as possible intermediate. These data corroborate the thermodynamical theory of ageing, according to which the exposure of cells to sublethal stresses of various natures can trigger SIPS, with possible modulations of this process by bioenergetics.
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            Ginsenosides chemistry, biosynthesis, analysis, and potential health effects.

            Ginsenosides are a special group of triterpenoid saponins that can be classified into two groups by the skeleton of their aglycones, namely dammarane- and oleanane-type. Ginsenosides are found nearly exclusively in Panax species (ginseng) and up to now more than 150 naturally occurring ginsenosides have been isolated from roots, leaves/stems, fruits, and/or flower heads of ginseng. Ginsenosides have been the target of a lot of research as they are believed to be the main active principles behind the claims of ginsengs efficacy. The potential health effects of ginsenosides that are discussed in this chapter include anticarcinogenic, immunomodulatory, anti-inflammatory, antiallergic, antiatherosclerotic, antihypertensive, and antidiabetic effects as well as antistress activity and effects on the central nervous system. Ginsensoides can be metabolized in the stomach (acid hydrolysis) and in the gastrointestinal tract (bacterial hydrolysis) or transformed to other ginsenosides by drying and steaming of ginseng to more bioavailable and bioactive ginsenosides. The metabolization and transformation of intact ginsenosides, which seems to play an important role for their potential health effects, are discussed. Qualitative and quantitative analytical techniques for the analysis of ginsenosides are important in relation to quality control of ginseng products and plant material and for the determination of the effects of processing of plant material as well as for the determination of the metabolism and bioavailability of ginsenosides. Analytical techniques for the analysis of ginsenosides that are described in this chapter are thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC) combined with various detectors, gas chromatography (GC), colorimetry, enzyme immunoassays (EIA), capillary electrophoresis (CE), nuclear magnetic resonance (NMR) spectroscopy, and spectrophotometric methods.
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              Cellular senescence, cancer and aging: the telomere connection.

              Telomeres are the repetitive DNA sequences and specialized proteins that form the distinctive structure that caps the ends of linear chromosomes. Telomeres allow cells to distinguish the chromosome ends from double strand DNA breaks. The telomeric structure prevents the degradation or fusion of chromosome ends, and thus is essential for maintaining the integrity and stability of eukaryotic genomes. In addition, and perhaps less widely appreciated, telomeres may also indirectly influence gene expression. The length, structure and organization of telomeres are regulated by a host of telomere-associated proteins, and can be influenced by basic cellular processes such as cell proliferation, differentiation, and DNA damage. In mammalian cells, telomere length and/or telomere structure have been linked to both cancer and aging. Here, we briefly review what is known about mammalian telomeres and the proteins that associate with them, and discuss the cellular and organismal consequences of telomere dysfunction and the evidence that cells with dysfunctional telomeres can contribute to cancer and aging phenotypes.
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                Author and article information

                Contributors
                Journal
                J Ginseng Res
                J Ginseng Res
                Journal of Ginseng Research
                Elsevier
                1226-8453
                2093-4947
                30 August 2018
                October 2019
                30 August 2018
                : 43
                : 4
                : 618-624
                Affiliations
                [1]College of Chinese Medicinal Material, Jilin Agricultural University, Changchun, China
                Author notes
                []Corresponding author. College of Chinese Medicinal Material, Jilin Agricultural University, 2888 Xincheng Street, Changchun, Jilin province, 130118, China. zhanglianxue126621@ 123456126.com
                [∗∗ ]Corresponding author. College of Chinese Medicinal Material, Jilin Agricultural University, Xincheng Street No. 2888, Changchun, Jilin province, 130118, China.
                [☆]

                Jiahong Han and Jing Xia contributed equally to this work.

                Article
                S1226-8453(18)30223-9
                10.1016/j.jgr.2018.07.009
                6823735
                31695568
                e8e334c1-3c6c-4103-9c85-582cd4f29d27
                © 2018 The Korean Society of Ginseng, Published by Elsevier Korea LLC.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 21 June 2018
                : 30 July 2018
                Categories
                Research Article

                chemotherapy,ginsenoside re,ginsenoside rk3,myelosuppression

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