title: Ginsenoside Rg1 improves bone marrow haematopoietic activity via extramedullary haematopoiesis of the spleen.
abstract: Cyclophosphamide (CY) is a chemotherapeutic agent used for cancer and immunological diseases. It induces cytotoxicity of bone marrow and causes myelosuppression and extramedullary haematopoiesis (EMH) in treated patients. EMH is characterized with the emergence of multipotent haematopoietic progenitors most likely in the spleen and liver. Previous studies indicated that a Chinese medicine, ginsenoside Rg1, confers a significant effect to elevate the number of lineage (Lin(-) ) Sca-1(+) c-Kit(+) haematopoietic stem and progenitor cells (HSPCs) and restore the function of bone marrow in CY-treated myelosuppressed mice. However, whether the amelioration of bone marrow by Rg1 accompanies an alleviation of EMH in the spleen was still unknown. In our study, the cellularity and weight of the spleen were significantly reduced after Rg1 treatment in CY-treated mice. Moreover, the number of c-Kit(+) HSPCs was significantly decreased but not as a result of apoptosis, indicating that Rg1 alleviated EMH of the spleen induced by CY. Unexpectedly, the proliferation activity of c-Kit(+) HSPCs was only up-regulated in the spleen, but not in the bone marrow, after Rg1 treatment in CY-treated mice. We also found that a fraction of c-Kit(+) /CD45(+) HSPCs was simultaneously increased in the circulation after Rg1 treatment. Interestingly, the effects of Rg1 on the elevation of HSPCs in bone marrow and in the peripheral blood were suppressed in CY-treated splenectomized mice. These results demonstrated that Rg1 improves myelosuppression induced by CY through its action on the proliferation of HSPCs in EMH of the spleen and migration of HSPCs from the spleen to the bone marrow.
authors.affiliation: Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung, Taiwan.
authors.forename: Hua-Hsing
authors.initials: HH
authors.lastname: Liu
authors.affiliation: Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung, Taiwan.
authors.forename: Fei-Peng
authors.initials: FP
authors.lastname: Chen
authors.affiliation: Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung, Taiwan.
authors.forename: Rong-Kai
authors.initials: RK
authors.lastname: Liu
authors.affiliation: Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung, Taiwan.
authors.forename: Chun-Lin
authors.initials: CL
authors.lastname: Lin
authors.affiliation: Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung, Taiwan.
authors.forename: Ko-Tung
authors.initials: KT
authors.lastname: Chang
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D001853:Bone Marrow / Q000503:physiopathology*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003520:Cyclophosphamide / Q000494:pharmacology*; D036145:Ginsenosides / Q000008:administration & dosage* / Q000627:therapeutic use; D006410:Hematopoiesis; D006411:Hematopoiesis, Extramedullary / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D051379:Mice; D013154:Spleen / Q000503:physiopathology*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D036145:Ginsenosides; D003520:Cyclophosphamide; C035054:ginsenoside Rg1
keywords: bone marrow; cyclophosphamide; extramedullary hematopoiesis; haematopoietic stem cells; spleen