Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, PR China.
BMC Complement Altern Med. 2010 Dec 21;10:79. doi: 10.1186/1472-6882-10-79.
Dozens of Traditional Chinese Medicine (TCM) formulas have been used for promotion of "blood production" for centuries, and we are interested in developing novel thrombopoietic medicines from these TCMs. Our previous studies have demonstrated the hematopoietic effects of DangGui BuXue Tong (DBT), a formula composed of Radix Angelicae Sinensis and Radix Astragali in animal and cellular models. As a step further to identify and characterize the active chemical components of DBT, we tested the hematopoietic and particularly, thrombopoietic effects of polysaccharide-enriched fractions from the root of Radix Angelicae Sinensis (APS) in this study.
A myelosuppression mouse model was treated with APS (10 mg/kg/day). Peripheral blood cells from APS, thrombopoietin and vehicle-treated samples were then counted at different time-points. Using the colony-forming unit (CFU) assays, we determined the effects of APS on the proliferation and differentiation of hematopoietic stem/progenitor cells and megakaryocytic lineages. Using a megakaryocytic cell line M-07e as model, we analyzed the cellular apoptosis progression with and without APS treatment by Annexin V, Mitochondrial Membrane Potential and Caspase 3 assays. Last, the anti-apoptotic effect of APS on cells treated with Ly294002, a Phosphatidylinositol 3-Kinse inhibitor (PI3K) was also tested.
In animal models, APS significantly enhanced not only the recovery of platelets, other blood cells and their progenitor cells, but also the formation of Colony Forming Unit (CFU). In M-07e cells, we observed the anti-apoptotic effect of APS. Treatment by Ly294002 alone increased the percentage of cells undergoing apoptosis. However, addition of APS to Ly294002-treated cells significantly reduced the percentage of cells undergoing apoptosis.
APS promotes hematopoiesis and thrombopoiesis in the mouse model. This effect likely resulted from the anti-apoptosis activity of APS and is likely to involve the PI3K/AKT pathway.
数十种中药方剂已被用于促进“生血”达数百年之久，我们有兴趣从这些中药方剂中开发新型促血小板生成药物。我们之前的研究已经在动物和细胞模型中证明了当归补血汤（DBT）的造血作用，DBT 是由当归和黄芪组成的方剂。作为进一步鉴定和描述 DBT 中活性化学成分的步骤，我们在这项研究中测试了当归根多糖富集部分（APS）的造血作用，尤其是促血小板生成作用。
用 APS（10mg/kg/天）处理骨髓抑制小鼠模型。然后在不同时间点计数 APS、血小板生成素和载体处理样品的外周血细胞。通过集落形成单位（CFU）测定，我们确定 APS 对造血干细胞/祖细胞和巨核细胞系增殖和分化的影响。使用巨核细胞系 M-07e 作为模型，我们通过 Annexin V、线粒体膜电位和 Caspase 3 测定分析有无 APS 处理时细胞凋亡的进展。最后，还测试了 APS 对用磷脂酰肌醇 3-激酶抑制剂（PI3K）Ly294002 处理的细胞的抗凋亡作用。
在动物模型中，APS 不仅显著增强了血小板、其他血细胞及其祖细胞的恢复，而且还增强了集落形成单位（CFU）的形成。在 M-07e 细胞中，我们观察到 APS 的抗凋亡作用。单独用 Ly294002 处理会增加细胞凋亡的百分比。然而，向 Ly294002 处理的细胞中加入 APS 可显著降低细胞凋亡的百分比。
APS 促进了小鼠模型中的造血和血小板生成。这种作用可能是由于 APS 的抗凋亡活性所致，可能涉及 PI3K/AKT 途径。
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