Research Center for Pharmacology & Toxicology, Institute of Medicinal Plant, Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Exp Biol Med (Maywood). 2011 Jun 1;236(6):729-35. doi: 10.1258/ebm.2011.010369.
Chemotherapy is the most common way to treat malignancies, but myelosuppression, one of its common side-effects, is a formidable problem. The present study described the protective role of dammarane sapogenins (DS), an active fraction from oriental ginseng, on myelosuppression induced by cyclophosphamide (CP) in mice. DS was orally administered at different dosages (37.5, 75, and 150 mg/kg) for 10 d after CP administration (200 mg/kg intraperitoneally). The results showed that DS increased the number of white blood cells (WBC) on day 3 and day 7 (P < 0.05), such that WBC levels were increased by 105.7 ± 29.5% at 75 mg/kg of DS on day 3 (P < 0.05, compared with the CP group). Similar results were observed in red blood cells and platelets in DS-treated groups. The colony-forming assay demonstrated that the depressed numbers of CFU-GM (colony-forming unit-granulocyte and macrophage), CFU-E (colony-forming unit-erythroid), BFU-E (burst-forming unit-erythroid), CFU-Meg (colony-forming unit-megakaryocyte) and CFU-GEMM (colony-forming unit-granulocyte, -erythrocyte, -monocyte and -megakaryocyte) induced by CP were significantly reversed after DS treatment. Moreover, the ameliorative effect of DS on myelosuppression was also observed in the femur by hematoxylin/eosin staining. In DS-treated groups, ConA-induced splenocyte proliferation was enhanced significantly at all the doses (37.5, 75, 150 mg/kg) on day 3 at the rate of 50.3 ± 8.0%, 77.6 ± 8.5% and 44.5 ± 8.4%, respectively, while lipopolysaccharide-induced proliferation was increased mainly on day 7 (P < 0.01), with an increased rate of 39.8 ± 5.6%, 34.9 ± 6.6% and 38.3 ± 7.3%, respectively. The thymus index was also markedly increased by 70.4% and 36.6% at 75 mg/kg on days 3 and 7, respectively, as compared with the CP group. In summary, DS has a protective function against CP-induced myelosuppression. Its mechanism might be related to stimulating hematopoiesis recovery, as well as enhancing the immunological function.
化疗是治疗恶性肿瘤最常用的方法，但骨髓抑制是其常见的副作用之一，是一个棘手的问题。本研究描述了达玛烷皂甙（DS），一种来自东方人参的活性成分，对环磷酰胺（CP）诱导的小鼠骨髓抑制的保护作用。CP 给药后（腹腔内 200mg/kg），DS 以不同剂量（37.5、75 和 150mg/kg）口服给药 10 天。结果表明，DS 在第 3 天和第 7 天增加白细胞（WBC）的数量（P<0.05），在第 3 天 75mg/kg 的 DS 组中，WBC 水平增加了 105.7±29.5%（P<0.05，与 CP 组相比）。在 DS 治疗组中，红细胞和血小板也观察到类似的结果。集落形成试验表明，CP 诱导的 CFU-GM（粒细胞-巨噬细胞集落形成单位）、CFU-E（红细胞集落形成单位）、BFU-E（红细胞爆式集落形成单位）、CFU-Meg（巨核细胞集落形成单位）和 CFU-GEMM（粒细胞、红细胞、单核细胞和巨核细胞集落形成单位）数量减少得到显著逆转。此外，在股骨通过苏木精/伊红染色也观察到 DS 对骨髓抑制的改善作用。在 DS 治疗组中，ConA 诱导的脾细胞增殖在第 3 天的所有剂量（37.5、75、150mg/kg）下均显著增强，分别为 50.3±8.0%、77.6±8.5%和 44.5±8.4%，而 LPS 诱导的增殖主要在第 7 天增加（P<0.01），分别增加了 39.8±5.6%、34.9±6.6%和 38.3±7.3%。与 CP 组相比，在第 3 天和第 7 天，75mg/kg 的 DS 组胸腺指数也分别显著增加了 70.4%和 36.6%。总之，DS 对 CP 诱导的骨髓抑制具有保护作用。其机制可能与刺激造血恢复以及增强免疫功能有关。
