Enhancing Erythropoiesis by a Phytoestrogen Diarylheptanoid from Curcuma comosa

Abstract

Erythropoietin (Epo) is widely used for the treatment of anemia; however, non-hematopoietic effects and cancer risk limit its clinical applications. Therefore, alternative molecules to improve erythropoiesis in anemia patients are urgently needed. Here, we investigated the potential effects of a phytoestrogen diarylheptanoid (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol, (ASPP 049) isolated from Curcuma comosa on promoting erythropoiesis. Treatment with C. comosa extract improved anemia symptoms demonstrated by increasing red blood cell numbers, hematocrit, and hemoglobin content in anemic mice. In addition, ASPP 049, the major compound isolated from C. comosa, enhanced the suboptimal Epo dosages to improve erythroid cell differentiation from hematopoietic stem cells, which was inhibited by the estrogen receptor (ER) antagonist, ICI 182,780. Moreover, the ASPP 049-activated Epo-Epo receptor (EpoR) complex subsequently induced phosphorylation of EpoR-mediated erythropoiesis pathways: STAT5, MAPK/ERK, and PI3K/AKT in Epo-sensitive UT-7 cells. Taken together, these results suggest that C. comosa extract and ASPP 049 increased erythropoiesis through ER- and EpoR-mediated signaling cascades. Our findings provide insight into the specific interaction between a phytoestrogen diarylheptanoid and Epo-EpoR in a hematopoietic system for the potential treatment of anemia.

Improving hematopoietic differentiation from human induced pluripotent stem cells by the modulation of Hippo signaling with a diarylheptanoid derivative

“…Magnetically sorted hiPSC-derived CD34 + cells were washed three times with cold PBS, lysed in protein-preservative buffers, and stepwise prepared for polyacrylamide gel electrophoresis, subsequently transferred to membranes by electroblotting as previously described [ 30 ]. Afterward, membranes were incubated with the primary antibodies: p-YAP1 (phospho-Ser127, 1:500, Abcam), YAP1 (1:1000, Abcam), p-WWTR1 (phospho-Ser89, 1:500, Invitrogen), WWTR1 (1:1000, Invitrogen), and GAPDH (1:20,000, Invitrogen), overnight at 4 °C.…”

“…Previous studies have revealed the constructive effects of ASPP 049, a diarylheptanoid isolated from Curcuma comosa [ 27 , 28 ], on an ex vivo CD34 + CD38 − CD90 + human HSC-culturing system. This compound potentially induces the cultured HSCs to have multi-lineage differentiation abilities in vitro, long-term reconstitution in vivo [ 29 ], as well as hematopoiesis improvement in an anemic mouse model [ 30 ]. However, the potential of HSC derivation from hiPSCs has not been investigated.…”