title: Echinacoside improves hematopoietic function in 5-FU-induced myelosuppression mice.
abstract: OBJECTIVE
  We aimed to investigate the effects of echinacoside (ECH) on hematopoietic function in 5-FU-induced bone marrow depression mice.
  
  
  METHODS
  In vitro, after stimulation with ECH, the proliferation ability of bone marrow (BM) cells and bone marrow stromal cells (BMSCs) derived from myelosuppression mice were assessed by CCK8 assay and morphology, respectively. In vivo, 5-FU-induced myelosuppression or control mice were intragastrically administrated with either ECH at 15 mg/kg or the equal volume of normal saline daily for 12 days before BM cells were isolated for colony-forming cell assay. Meanwhile, BMSCs were cultured for 4 weeks before cells were observed for growth pattern, cell culture supernatants were collected for GM-CSF secretion by ELISA, and RNA of the cells were extracted for EPO and GM-CSF RT-PCR. BM cells or BMSCs stimulated with ECH for 24 h or 48 h were collected for protein extraction and Western blotting.
  
  
  RESULTS
  ECH stimulated the growth of BM cells but not BMSCs derived from 5-FU treated mice. The intragastric administration of ECH in 5-FU treated mice could increase the number of total hematopoietic progenitor cells and GM progenitor cells to healthy control mice level, but not BFU progenitor cells. BMSCs from ECH treated myelosuppression mice grew more vigorously and expressed more GM-CSF, but not EPO. ECH activated the PI3K signaling pathway in 5-FU suppressed BM cells.
  
  
  CONCLUSIONS
  ECH could improve the hematopoietic function of bone marrow in 5-FU-induced myelosuppression mice. ECH can be considered as an alternative effective therapy for patients during chemotherapy or HSC transplantation.
authors.affiliation: Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China; Department of Medical Microbiology and Parasitology, Research Center of Infection and Immunity, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: Saisai
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Medical Microbiology and Parasitology, Research Center of Infection and Immunity, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Zheng
authors.affiliation: Engineering Technology Research Center of Glue of Traditional Medicine, Shandong Dongeejiao Co., Ltd, Shandong 252201, China.
authors.forename: Shousheng
authors.initials: S
authors.lastname: Tian
authors.affiliation: Engineering Technology Research Center of Glue of Traditional Medicine, Shandong Dongeejiao Co., Ltd, Shandong 252201, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Medical Microbiology and Parasitology, Research Center of Infection and Immunity, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: Yongchol
authors.initials: Y
authors.lastname: Pak
authors.affiliation: Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China; Department of Medical Microbiology and Parasitology, Research Center of Infection and Immunity, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Medical Microbiology and Parasitology, Research Center of Infection and Immunity, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China. Electronic address: jingqian@zju.edu.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Qian
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000187:drug effects / Q000502:physiology; D001855:Bone Marrow Diseases / Q000188:drug therapy* / Q000209:etiology; D049109:Cell Proliferation / Q000187:drug effects; D003114:Colony-Forming Units Assay; D017931:DNA Primers / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects*; D006027:Glycosides / Q000737:chemistry / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects*; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D006027:Glycosides; C060297:echinacoside; D005472:Fluorouracil
keywords: Echinacoside; GM-CSF; Hematopoietic; Myelosuppression; PI3K signaling pathway