ZhenQi FuZheng Formula Improves Mouse Hematopoietic Function after Cyclophosphamide-Induced Damage via Enhancing Macrophage Colony-Stimulating Factor Concentrations

Abstract Background: Among the hematopoietic system, bone marrow has been recognized as the major source of hematopoietic progenitor cells (HPCs). Immuosuppression can inhibit the growth of bone marrow cells and cyclophosphamide (CTX) has been reported to induce myelosuppression. Regeneration of the immune system and hematopoietic function has become a primary problem in tumor adjuvant therapy. The present study investigated the effects of ZhenQi FuZheng formula (ZQFZ) on hematopoietic function in cells and murine models of cyclophosphamide(CTX)-induced immunosuppression and hematopoietic dysfunction. Methods: According to antibody chip analysis and enzyme-linked immunosorbent assay, ZQFZ regulated seven cytokines in serum and the spleen. Results: In Nrf2-siRNA transfected K562 cells, the regulatory effects of ZQFZ on the expression concentrations of macrophage colony-stimulating factor (M-CSF) and hematopoietic related proteins were strongly abolished. In immunosuppressed mice, ZQFZ enhanced the NK cell activities and regulated the concentrations of cytokines related to immune function. ZQFZ induced proliferation and differentiation, and upregulated the expression of hematopoietic-related proteins, including p90 ribosomal S6 kinases 1 (RSK1p90), c-Myc, and ETS transcription factor in CHRF and/or K562 cells. In mice with hematopoietic dysfunction, ZQFZ contributed to the recovery of blood cell concentrations in peripheral blood to normal values and enhanced the percentages of B lymphocytes (LYs) and juvenile cells in the bone marrow.Conclusions: In spleens of hematopoiesis damaged mice and primary cultured bone marrow cells, ZQFZ upregulated the expression concentrations of NF-E2-related Factor 2 (Nrf2) and its downstream proteins, and the activation of nuclear factor kappa-B. ZQFZ showed remarkably beneficial effects on the bone marrow hematopoietic system, at least partially, by enhancing the concentrations of M-CSF.