Abstract
Sarcodon imbricatus, a rare medicinal and edible fungus, has various pharmacological bioactivities. We investigated the effects of S. imbricatus polysaccharides (SIPS) on hematopoietic function and identified the underlying mechanisms using in vitro experiments with CHRF, K562, and bone marrow mononuclear cells (BMMNCs) and in vivo experiments with a mouse model of cyclophosphamide-induced hematopoietic dysfunction. We found that SIPS induced proliferation and differentiation of CHRF and K562 cells and upregulated the expression of hematopoietic-related proteins, including p90 ribosomal S6 kinases (RSK1p90), c-Myc, and ETS transcription factor, in the two cell lines. After 28 days of treatment, SIPS enhanced the bodyweight and thymus indices of the mice, alleviated enlargement of the spleen and liver, and contributed to the recovery of peripheral blood to normal levels. More importantly, the percentages of B lymphocytes and hematopoietic stem cells or hematopoietic progenitor cells were significantly elevated in bone marrow. Based on an antibody chip analysis and enzyme-linked immunosorbent assay, SIPS were found to successfully regulate 12 cytokines to healthy levels in serum and spleen. The cytokines included the following: interleukins 1Ra, 2, 3, 4, 5, and 6, tumor necrosis factor α, interferon−γ, granulocyte colony-stimulating factor (G-CSF) and macrophage colony-stimulating factor (M-CSF), C-C motif chemokine1, and monocyte chemoattractant protein−1. Moreover, SIPS upregulated the phosphorylation levels of janus kinase 2 (JAK2) and the signal transducer and activator of transcription 3 (STAT3) in the spleen, and similar results were validated in CHRF cells, K562 cells, and BMMNCs. The data indicate that SIPS activated the JAK2/STAT3 pathway, possibly by interactions among multiple cytokines, particularly G-CSF. We found that SIPS was remarkably beneficial to the bone marrow hematopoietic system, and we anticipate that it could improve myelosuppression induced by long-term radiotherapy or chemotherapy.
Highlights
Chemotherapy and radiotherapy are the main treatments for cancer, but they do not kill only cancer cells
To further reveal the role of S. imbricatus polysaccharides (SIPS) in promoting hematopoietic recovery, we investigated the effects of the G-CSFmediated janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway
Effects of SIPS on bodyweight and organ indices in mice with hematopoietic dysfunction Compared to the control mice, the mice that received continual injections of CTX had a sharp decrease in bodyweight, splenomegaly, enlargement of the liver, and reduction of the thymus (P < 0.001; Table 1)
Summary
Chemotherapy and radiotherapy are the main treatments for cancer, but they do not kill only cancer cells They destroy healthy cells[1] or, worse, damage the hematopoietic system[2]. Chemosynthetic myeloprotective agents cause adverse reactions, such as peripheral leucopenia and myelosuppression[11] Because of their pharmacologic properties and low level of adverse effects, effective active ingredients from herbs and/or fungi have recently been applied to promote recovery of hematopoietic function[12,13]. Angelica sinensis polysaccharides ameliorate stress-induced premature senescence by protecting bone marrow stromal cells from chemotherapeutic injury, and further improve their hematopoietic function by mitigating oxidative damage to stromal cells[15]
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