Total ginsenosides enhance γ-globin expression and fetal hemoglobin production in β-thalassemia models

Introduction β-thalassemia is a genetic hemoglobinopathy characterized by defective β-globin synthesis and ineffective erythropoiesis. Pharmacological induction of fetal hemoglobin (HbF) via γ-globin gene activation represents a promising therapeutic strategy. Total ginsenosides (TG), the principal active constituents of Panax ginseng , have shown epigenetic and transcriptional modulatory properties, yet their role in HbF induction remains unexplored. Methods We evaluated the HbF-inducing potential of TG using human erythroleukemia cell line (K562), primary erythroid precursor cells (ErPCs) derived from CD34 + umbilical cord blood, and Townes transgenic mice. TG was administered at varying concentrations in vitro (25–400 μg/mL) and in vivo (50–800 mg/kg/day for 14 days). HbF and γ-globin expression were quantified by flow cytometry, immunofluorescence, and RT-qPCR. Hemoglobin content, cell viability, and hepatic histology were also assessed. Results TG significantly induced HbF production and γ-globin gene expression in both cellular models in a dose-dependent manner. In K562 cells, 200 μg/mL TG elevated γ-globin mRNA by 4.29-fold; in ErPCs, the increase was 1.46-fold. HbF-positive cell populations rose markedly without impairing cell viability or morphology. In vivo, TG treatment at 200 and 400 mg/kg led to 2.8- and 3.1-fold increases in F-cell proportions, respectively, surpassing hydroxyurea controls. No hepatotoxicity was observed upon histopathological examination. Discussion These findings establish TG as a potent, well-tolerated inducer of HbF through transcriptional activation of the γ-globin gene. Its efficacy across erythroid cell lines, primary progenitor cells, and transgenic mouse models underscores its translational potential as a natural therapeutic agent for β-thalassemia.