Ginseng-derived panaxadiol saponins promote hematopoiesis recovery in cyclophosphamide-induced myelosuppressive mice: Potential novel treatment of chemotherapy-induced cytopenias

  • Xin Sun
  • Yan-na Zhao
  • Song Qian
  • Rui-lan Gao
  • Li-ming Yin
  • Li-pei Wang
  • Beng-hock Chong
  • Su-zhan Zhang
Original Article

Abstract

Objective

To investigate the potential efficacy of panaxadiol saponins component (PDS-C), a biologically active fraction isolated from total ginsenosides, to reverse chemotherapy-induced myelosuppression and pancytopenia caused by cyclophamide (CTX).

Methods

Mice with myelosuppression induced by CTX were treated with PDS-C at a low- (20 mg/kg), moderate- (40 mg/kg), or high-dose (80 mg/kg) for 7 consecutive days. The level of peripheral white blood cell (WBC), neutrophil (NEU) and platelet (PLT) were measured, the histopathology and colony formation were observed, the protein kinase and transcription factors in hematopoietic cells were determined by immunohistochemical staining and Western blot.

Results

In response to PDS-C therapy, the peripheral WBC, NEU and PLT counts of CTX-induced myelosuppressed mice were significantly increased in a dose-dependent manner. Similarly, bone marrow histopathology examination showed reversal of CTX-induced myelosuppression with increase in overall bone marrow cellularity and the number of hematopoietic cells (P<0.01). PDS-C also promoted proliferation of granulocytic and megakaryocyte progenitor cells in CTX-treated mice, as evidenced by significantly increase in colony formation units-granulocytes/monocytes and -megakaryocytes (P<0.01). The enhancement of hematopoiesis by PDS-C appears to be mediated by an intracellular signaling pathway, this was evidenced by the up-regulation of phosphorylated mitogen-activated protein kinase (p-MEK) and extracellular signal-regulated kinases (p-ERK), and receptor tyrosine kinase (C-kit) and globin transcription factor 1 (GATA-1) in hematopoietic cells of CTX-treated mice (P<0.05).

Conclusions

PDS-C possesses hematopoietic growth factor-like activities that promote proliferation and also possibly differentiation of hematopoietic progenitor cells in myelosuppressed mice, probably mediated by a mechanism involving MEK and ERK protein kinases, and C-kit and GATA-1 transcription factors. PDS-C may potentially be a novel treatment of myelosuppression and pancytopenia caused by chemotherapy.

Keywords

panaxadiol saponins component ginsenosides chemotherapy-induced myelosuppression mitogen-activated protein kinase extracellular signal-regulated kinase receptor tyrosine kinase globin transcription factor 1 Chinese medicine 

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Copyright information

© Chinese Association of the Integration of Traditional and Western Medicine and Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Xin Sun
    • 1
    • 2
  • Yan-na Zhao
    • 3
  • Song Qian
    • 3
  • Rui-lan Gao
    • 3
  • Li-ming Yin
    • 3
  • Li-pei Wang
    • 3
  • Beng-hock Chong
    • 4
  • Su-zhan Zhang
    • 1
  1. 1.Department of Oncology, The Second Affiliated HospitalMedical College of Zhejiang UniversityHangzhouChina
  2. 2.Department of OncologyZhejiang Provincial People’s HospitalHangzhouChina
  3. 3.Institution of Hematology ResearchThe First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhouChina
  4. 4.Department of HematologySt George Sutherland HospitalSydneyAustralia

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