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

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.