Studies of the effects and mechanisms of ginsenoside Re and Rk₃ on myelosuppression induced by cyclophosphamide

Jiahong Han,Jing Xia,Lianxue Zhang,Enbo Cai,Yan Zhao,Xuan Fei,Xiaohuan Jia,He Yang,Shuangli Liu 고려인삼학회 2019 Journal of Ginseng Research Vol.43 No.4

Background: Ginsenoside Re (Re) is one of the major components of Panax ginseng Meyer. Ginsenoside Rk₃ (Rk₃) is a secondary metabolite of Re. The aim of this study was to investigate and compare the effects and underlying mechanisms of Re and Rk₃ 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 Rk₃ 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 G₀/G₁ phase cells, and increase the proliferation index. Finally, Re and Rk₃ could upregulate the expression of bcl-2, whereas they could downregulate the expression of bax and caspase-3. Conclusion: Re and Rk₃ could improve the hematopoietic function of myelosuppressed mice. The effect of Rk₃ 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 Rk₃ on myelosuppression.

Compatibility effects of ginseng and Ligustrum lucidum Ait herb pair on hematopoietic recovery in mice with cyclophosphamide-induced myelosuppression and its material basis

Jiahong Han,Min Dai,Yan Zhao,Enbo Cai,Lianxue Zhang,Xiaohuan Jia,Nian Sun,Xuan Fei,Hui Shu 고려인삼학회 2020 Journal of Ginseng Research Vol.44 No.2

Background: Ginseng (G) and Ligustrum lucidum Ait (LLA) are core traditional Chinese medicines intreating myelosuppression formula. The present study was designed to profile effect of G and LLA herbpair (G-LLA) on myelosuppressed mice. Methods: The mice myelosuppression model was established by intraperitoneal (i.p.) injection ofcyclophosphamide (Cy). Hematopoietic function of bone marrow was measured by hemopoietic progenitorcell culture and peripheral blood count, and serum hemopoietic factors were tested by enzymelinkedimmunosorbent assay. Bone marrow cell cycle was performed by flow cytometry. HPLC was usedto measure 20 potential chemical components related to myelosuppression, including ginsenoside Rg1,Re, Rb1, Rc, Rb2, Rb3, Rd, Rk3, Rh4, 20 (S)-Rg3, 20 (R)-Rg3, Rk1, Rg5, salidroside, and so on. Results: G, LLA, and G-LLA improved the amount of peripheral blood cells and bone marrow cellsof myelosuppressed mice (P < 0.01). They significantly increased the colony quantity of colony-formingunitegranulocyte macrophage, burst-forming unit erythroid, colony-forming unit erythroid, and colony-forming unit megakaryocyte and amount of G2/M and S phase cells (P < 0.01). They also significantlydecreased the amount of hematopoiesis-related cytokines (P < 0.01). The content of chemicalcomponents in G-LLA changed, and the change of rare saponin was the most obvious. Conclusion: These results show that G-LLA herb pair might produce synergistic or complementarycompatibility effects on bone marrow suppression after chemotherapy. It suggests that the substancebasis of G-LLA for treating bone marrow suppression may be effective chemical components.

Studies of the effects and mechanisms of ginsenoside Re and Rk₃ on myelosuppression induced by cyclophosphamide

Han, Jiahong,Xia, Jing,Zhang, Lianxue,Cai, Enbo,Zhao, Yan,Fei, Xuan,Jia, Xiaohuan,Yang, He,Liu, Shuangli The Korean Society of Ginseng 2019 Journal of Ginseng Research Vol.43 No.4

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.

Compatibility effects of ginseng and Ligustrum lucidum Ait herb pair on hematopoietic recovery in mice with cyclophosphamide-induced myelosuppression and its material basis

Han, Jiahong,Dai, Min,Zhao, Yan,Cai, Enbo,Zhang, Lianxue,Jia, Xiaohuan,Sun, Nian,Fei, Xuan,Shu, Hui The Korean Society of Ginseng 2020 Journal of Ginseng Research Vol.44 No.2

Background: Ginseng (G) and Ligustrum lucidum Ait (LLA) are core traditional Chinese medicines in treating myelosuppression formula. The present study was designed to profile effect of G and LLA herb pair (G-LLA) on myelosuppressed mice. Methods: The mice myelosuppression model was established by intraperitoneal (i.p.) injection of cyclophosphamide (Cy). Hematopoietic function of bone marrow was measured by hemopoietic progenitor cell culture and peripheral blood count, and serum hemopoietic factors were tested by enzyme-linked immunosorbent assay. Bone marrow cell cycle was performed by flow cytometry. HPLC was used to measure 20 potential chemical components related to myelosuppression, including ginsenoside Rg₁, Re, Rb₁, Rc, Rb₂, Rb₃, Rd, Rk₃, Rh₄, 20 (S)-Rg₃, 20 (R)-Rg₃, Rk₁, Rg₅, salidroside, and so on. Results: G, LLA, and G-LLA improved the amount of peripheral blood cells and bone marrow cells of myelosuppressed mice (P < 0.01). They significantly increased the colony quantity of colony-forming unit-granulocyte macrophage, burst-forming unit-erythroid, colony-forming unit-erythroid, and colony-forming unit-megakaryocyte and amount of G₂/M and S phase cells (P < 0.01). They also significantly decreased the amount of hematopoiesis-related cytokines (P < 0.01). The content of chemical components in G-LLA changed, and the change of rare saponin was the most obvious. Conclusion: These results show that G-LLA herb pair might produce synergistic or complementary compatibility effects on bone marrow suppression after chemotherapy. It suggests that the substance basis of G-LLA for treating bone marrow suppression may be effective chemical components.