Echinacoside improves hematopoietic function in 5-FU-induced myelosuppression mice

Abstract

Aims: We aimed to investigate the effects of echinacoside (ECH) on hematopoietic function in 5-FU-induced bone marrow depression mice.

Main 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.

Key findings: 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.

Significance: 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.

Keywords: Echinacoside; GM-CSF; Hematopoietic; Myelosuppression; PI3K signaling pathway.