Nanocurcumin as a novel stimulator of megakaryopoiesis that ameliorates chemotherapy-induced thrombocytopenia in mice

Aims: Platelet production improvement can resolve concerns about the limitations of external platelet supply and platelet transfusion in thrombocytopenia patients. To this end, scientists encourage to induce the generation of megakaryocyte and platelet. Curcumin is a safe ingredient of turmeric that affects various cellular pathways. The effect of this component on platelet production has not been yet reported. Main methods: Our in vitro experiments include the investigation of the effects of nanocurcumin on megakaryocytes production from K562 cells and hematopoietic stem cells via megakaryocyte markers expression, DNA content, ROS, and morphologic analysis, and CFC assay. The regulatory functions of MAPKs pathways were also determined. In the in vivo study tissue distribution of nanocurcumin was determined and two treatment schedules were used to evaluate the capability of nanocurcumin to prevent the occurrence of Busulfan-induced thrombocytopenia in the mouse model. Key finding: In vitro evidences demonstrated that nanocurcumin can induce MK production from K562 cells and hematopoietic stem cells. Inhibition of ERK1/2 and JNK pathways arrested this activity. In vivo experiments showed the uptake of nanocurcumin by tissues in mice. Administration of nanocurcumin could preserve bone marrow integrity and increase of the number of circulating platelets in the Busulfan-treated mice models. Significance: Our results have demonstrated that nanocurcumin administration can be useful for the improvement of megakaryocytes and platelet generation in vitro. This component may be exerting these beneficial effects on megakaryopoiesis by modulating ERK1/2 and JNK pathways. As well as nanocurcumin has the potential to prevent thrombocytopenia in chemotherapy threated mice.