title: Protective effect of dammarane sapogenins against chemotherapy-induced myelosuppression in mice.
abstract: 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.
authors.affiliation: Research Center for Pharmacology & Toxicology, Institute of Medicinal Plant, Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Yang
authors.forename: Shuping
authors.initials: S
authors.lastname: Xu
authors.forename: Qiuxia
authors.initials: Q
authors.lastname: Xu
authors.forename: Xinmin
authors.initials: X
authors.lastname: Liu
authors.forename: Yue
authors.initials: Y
authors.lastname: Gao
authors.forename: Andre
authors.initials: A
authors.lastname: Steinmetz
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.forename: Tianshan
authors.initials: T
authors.lastname: Wang
authors.forename: Guosong
authors.initials: G
authors.lastname: Qiu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D003114:Colony-Forming Units Assay / Q000379:methods; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects*; D064420:Drug-Related Side Effects and Adverse Reactions; D005269:Femur / Q000473:pathology; D006651:Histocytochemistry; D007958:Leukocyte Count; D051379:Mice; D019653:Myeloablative Agonists / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D005894:Panax / Q000737:chemistry; D020011:Protective Agents / Q000008:administration & dosage* / Q000302:isolation & purification; D012502:Sapogenins / Q000008:administration & dosage* / Q000302:isolation & purification; D013234:Stem Cells; D014315:Triterpenes / Q000008:administration & dosage* / Q000302:isolation & purification; D000097669:Dammaranes
chemical_list: D003520:Cyclophosphamide; D019653:Myeloablative Agonists; D020011:Protective Agents; D012502:Sapogenins; D014315:Triterpenes; D000097669:Dammaranes