Effect of salidroside on bone marrow haematopoiesis in a mouse model of myelosuppressed anaemia

Abstract

This study was designed to investigate the effect of salidroside (SAL) on bone marrow haematopoiesis in a mouse model of myelosuppressed anemia. After the mouse model was established by 60Co γ irradiation and cyclophosphamide, pancytopenia and a sharp reduction in bone marrow stromal cells and bone marrow haematopoietic stem cells (lineage-Sca1+c-kit+) were observed. This was greatly alleviated by SAL (25 mg/kg, 50 mg/kg, 100 mg/kg) in a dose-dependent manner (50% effective dose value of 35.7 mg/kg and 61.2 mg/kg, respectively), followed by a distinct increment in anti-apoptotic protein Bcl-2. For cell culture in vitro, treatment with SAL resulted in a significant recovery of burst-forming unit-erythroids, and colony-forming unit-granulocyte macrophages on Day 7, and colony-forming unit-erythroids on Day 3, dose-dependently, but not of colony-forming unit-megakaryocyte macrophages. Inoculation of bone marrow cells derived from SAL-administrated donor mice resulted in a 60% survival of recipient mice at the high dose of 100 mg/kg SAL at 2 months after surgery. SAL appeared to be able to stimulate the restoration of bone marrow haemopoietic regulation in myelosuppressed anemia. Based on the downregulation of Fas ligand associated with the expression of Caspase-3 at the protein level, it was suggested that SAL might have an anti-apoptotic effect on bone marrow cells in the Fas-apoptotic pathway of Fas/FasL-caspase-3.

Keywords: bone marrow haematopoiesis; hematopoietic progenitors; myelosuppressed anemia; salidroside.

Fig. 1.

Effects of SAL on pancytopenia in an irradiated mouse model of myelosuppressed anemia (A: PLT, platelet; B: RBC, red blood cells; C: WBC, white blood cells; D: molecular structure of SAL).

Fig. 2.

Effects of SAL on the recovery of hematopoietic progenitors in the bone marrow (A: CFU-E; B: BFU-E; C: CFU-GM; D: CFU-Meg; E: the counting of colony-forming units). All data represented in the form of mean ± SEM (Norm: n = 10; vehicle: n = 7; 25 mg/kg SAL: n = 9; 50 mg/kg SAL: n = 10, 100 mg/kg SAL: n = 10). ‘a’ indicates a significant difference compared with the normal group, ‘b’ indicates a significant difference compared with the vehicle group.

Fig. 3.

Effect of SAL on the proliferation of BMSCs and the number of HSC lineage⁻Sca1⁺c-kit⁺ cells (A: cell counting of BMSCs; B: ED₅₀ of BMSCs; C: cell counting of HSC c-kit⁺ cells; D: ED₅₀ of HSC c-kit⁺ cells). ‘a’ indicates a significant difference compared with the normal group, ‘b’ indicates a significant difference compared with the vehicle group.

Fig. 4.

The expressions of apoptins (A: Bcl-2 and Bax, B: Caspase-3 and FasL) in modeling mice after dose-dependent treatment. Data were normalized on the basis of β-actin levels. All data are represented in the form of mean ± SEM (Vehicle: n = 7; 25 mg/kg SAL: n = 9; 50 mg/kg SAL: n = 10, 100 mg/kg SAL: n = 10). ‘b’ indicates a significant difference compared with the vehicle group.

Fig. 5.

Effects of SAL on the relative survival rate of myelosuppressed anemic mice after bone marrow transplantation (n = 10).