Epigallocatechin promotes megakaryocyte differentiation via ERα-dependent SRC/PI3K/AKT signaling for thrombocytopenia treatment.

ETHNOPHARMACOLOGICAL RELEVANCE: Sanguisorba officinalis L., a traditional Chinese hemostatic herb, is described in classical texts as having the dual function of "cooling and tonifying the blood." Modern clinical studies have confirmed its significant efficacy against myelosuppression induced by cancer therapy, notably in elevating platelet counts in patients. However, the specific active components responsible for this effect and their underlying mechanisms remain unelucidated.

AIM OF THE STUDY: Building on the traditional hemostatic efficacy of Sanguisorba officinalis L., this study elucidates the effects and mechanisms of its active monomer, epigallocatechin (EGC), in promoting megakaryocyte differentiation and platelet production for the treatment of thrombocytopenia.

MATERIALS AND

METHODS

In this study we evaluated the ability of EGC to promote megakaryocyte differentiation of model cells in vitro. Its hematopoietic effects in vivo were further assessed using zebrafish and mouse models of RIT. To pinpoint the core targets of EGC against RIT, we utilized network pharmacology, complemented by experimental validation with molecular biology techniques to elucidate its pro-hematopoietic mechanisms mediated through the estrogen receptor.

RESULTS

EGC effectively enhanced megakaryocyte differentiation and platelet production in vitro and in vivo, without detectable toxicity. Integrated network pharmacology and molecular validation revealed ERα-mediated signaling as the primary mechanism underlying EGC's activity. Mechanistically, EGC promoted megakaryocyte differentiation by activating ERα-mediated SRC/PI3K/AKT signaling and modulating hematopoietic transcription factors.

CONCLUSIONS

EGC promotes megakaryocyte differentiation via ERα-mediated activation of the SRC/PI3K/AKT pathway and subsequent regulation of hematopoietic transcription factors for the treatment of thrombocytopenia.