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Panaxdiol Saponins Component Promotes Hematopoiesis and Modulates T Lymphocyte Dysregulation in Aplastic Anemia Model Mice

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Abstract

Objective

To investigate the potential efficacy of panaxadiol saponins component (PDS-C) in the treatment of aplastic anemia (AA) model mice.

Methods

Totally 70 mice were divided into 7 groups as follows: normal, model, low-, medium-, high-dose PDS-C (20, 40, 80 mg/kg, namely L-, M-, H-PDS-C), cyclosporine (40 mg/kg), and andriol (25 mg/kg) groups, respectively. An immune-mediated AA mouse model was established in BALB/c mice by exposing to 5.0 Gy total body irradiation at 1.0 Gy/min, and injecting with lymphocytes from DBA mice. On day 4 after establishment of AA model, all drugs were intragastrically administered daily for 15 days, respectively, while the mice in the normal and model groups were administered with saline solution. After treatment, the peripheral blood counts, bone marrow pathological examination, colony forming assay of bone marrow culture, T lymphocyte subpopulation analysis, as well as T-bet, GATA-3 and FoxP3 proteins were detected by flow cytometry and Western blot.

Results

The peripheral blood of white blood cell (WBC), platelet, neutrophil counts and hemoglobin (Hb) concentration were significantly decreased in the model group compared with the normal group (all P<0.01). In response to 3 dose PDS-C treatment, the WBC, platelet, neutrophil counts were significantly increased at a dose-dependent manner compared with the model group (all P<0.01). The myelosuppression status of AA was significantly reduced in M-, H-PDS-C groups, and hematopoietic cell quantity of bone marrow was more abundant than the model group. The colony numbers of myeloid, erythroid and megakaryocytic progenitor cells in the model group were less than those of the normal mice in bone marrow culture, while, PDS-C therapy enhanced proliferation of hematopoietic progenitor cells by significantly increasing colony numbers (all P<0.01). Furthermore, PDS-C therapy increased peripheral blood CD3+ and CD3+CD4+ cells and reduced CD3+CD8+ cells (P<0.05 or P<0.01). Meanwhile, PDS-C treatment at medium- and high doses groups also increased CD4+CD25+FoxP3+ cells, downregulated T-bet protein expression, and upregulated GATA-3 and FoxP3 protein expressions in spleen cells (P<0.05).

Conclusion

PDS-C possesses dual activities, promoting proliferation hematopoietic progenitor cells and modulating T lymphocyte immune functions in the treatment of AA model mice.

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Authors and Affiliations

  1. Institution of Hematology Research, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006, China

    Zhi-yin Zheng, Xiao-ling Yu, Tie-ying Dai, Li-ming Yin, Yan-na Zhao, Min Xu, Hai-feng Zhuang & Rui-lan Gao

  2. Department of Hematology, St George Hospital, St George Clinical School, University of New South Wales, Kogarah, NSW, 2217, Australia

    Beng Hock Chong

Authors
  1. Zhi-yin Zheng
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  2. Xiao-ling Yu
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  3. Tie-ying Dai
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  4. Li-ming Yin
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  5. Yan-na Zhao
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  6. Min Xu
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  7. Hai-feng Zhuang
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  8. Beng Hock Chong
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  9. Rui-lan Gao
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Contributions

Gao RL, Zheng ZY and Chong BH conceived of the study, designed, supervised the experiments and wrote the manuscript. Yu XL performed preparation and analysis of PDS-C. Dai TY, Yin LM, Zhao YN, Xu M and Zhuang HF performed animal and cell experiments.

Corresponding author

Correspondence to Rui-lan Gao.

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Conflict of Interest

The authors declare that they have no conflict of interest

Supported by the National Natural Science Foundation of China (No. 81774068), Medical and Health Key Project of Zhejiang Province (No. 2011ZDA021), Zhejiang Provincial Natural Science Foundation of China (No. LY14H280004)

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Zheng, Zy., Yu, Xl., Dai, Ty. et al. Panaxdiol Saponins Component Promotes Hematopoiesis and Modulates T Lymphocyte Dysregulation in Aplastic Anemia Model Mice. Chin. J. Integr. Med. 25, 902–910 (2019). https://doi.org/10.1007/s11655-019-3049-z

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  • DOI: https://doi.org/10.1007/s11655-019-3049-z

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