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Total saponins of Panax ginseng (TSPG) promote erythroid differentiation of human CD34⁺ cells via EpoR-mediated JAK₂/STAT₅ signaling pathway

Chen, D., Zuo, G., Li, C., Hu, X., Guan, T., Jiang, R., Li, J., Lin, X., Li, F., Luo, C., Wang, H., Lei, C., Long, X., Wang, Y., Wang, J.
Journal of ethnopharmacology 2009 v.126 no.2 pp. 215-220
Panax ginseng, medicinal plants, herbal medicines, medicinal properties, saponins, plant extracts, hematopoiesis, mechanism of action, cell differentiation, stem cells, erythrocytes, umbilical cord, flow cytometry, hemoglobin, reverse transcriptase polymerase chain reaction, messenger RNA, protein synthesis, gene expression, biochemical pathways, signal transduction, cultured cells, cell lines, in vitro studies
Ethnopharmacological relevance: Total saponins of Panax ginseng (TSPG), main constituents extracted from Panax ginseng, a highly valued traditional Chinese medicine, have been shown to be an effective agent on hematopoiesis. Objective: To investigate the effect and mechanism underlying in which TSPG promote human CD34⁺ hematopoietic stem and progenitor cells to differentiate into erythroid-lineage cells. Materials and methods: The effect of TSPG on erythroid differentiation of purified CD34⁺ cells derived from umbilical cord blood (UCB) was determined by methylcellulose assay system and colorimetry for hemoglobin content. The changes of EpoR expression in umbilical cord blood mononuclear cells (UCB-MNCs) and purified CD34⁺ cells were detected with Western blotting and flow cytometry, respectively, and observed under laser scanning confocal microscope (LSCM). RT-PCR was performed to examine EpoR mRNA expression in CD34⁺ cells. The effects of TSPG-pretreatment on Epo-induced JAK₂ and STAT₅ tyrosine phosphorylation were analyzed by immunoprecipitation. Results: The addition of TSPG (20-70mg/L) increased the colony formation rate of BFU-E. TSPG (50mg/L) alone used significantly increased the hemoglobin content, the addition of AG490 evidently reduced TSPG-induced elevation of hemoglobin content. TSPG increased the expression of EpoR on the surface membrane of CD34⁺ cells but did not change the expression of EpoR in total UCB-MNCs. TSPG also increased the expression of EpoR mRNA in CD34⁺ cells. TSPG markedly enhanced Epo-induced tyrosine phosphorylation of JAK₂ and STAT₅ in UCB-MNCs. Conclusion: These findings suggest that TSPG may enhance the erythroid differentiation of hematopoietic stem and progenitor cells via Epo/EpoR-mediated JAK₂/STAT₅ signaling pathway.