Ginsenoside Rg1 promotes fetal hemoglobin production in vitro: A potential therapeutic avenue for β-thalassemia

β-thalassemia, a globally prevalent genetic disorder, urgently requires innovative treatment options. Fetal hemoglobin (HbF) induction stands as a key therapeutic approach. This investigation focused on Ginsenoside Rg1 from the Panax genus for HbF induction. Employing K562 cells and human erythroid precursor cells (ErPCs) derived from neonatal cord blood, the study tested Rg1 at different concentrations. We measured its effects on γ-globin mRNA levels and HbF expression, alongside assessments of cell proliferation and differentiation. In K562 cells, Rg1 at 400 μM significantly increased γ-globin mRNA expression by 4.24 ± 1.08-fold compared to the control. In ErPCs, the 800 μM concentration was most effective, leading to an over 80% increase in F-cells and a marked upregulation in HbF expression. Notably, Rg1 did not adversely affect cell proliferation or differentiation, with the 200 μM concentration showing an increase in γ-globin mRNA by 2.33 ± 0.58-fold, and the 800 μM concentration enhancing HbF expression by 2.59 ± 0.03-fold in K562 cells. Our results underscore Rg1's potential as an effective and safer alternative for β-thalassemia treatment. By significantly enhancing HbF levels without cytotoxicity, Rg1 offers a notable advantage over traditional treatments like Hydroxyurea. While promising, these in vitro findings warrant further in vivo exploration to confirm Rg1's therapeutic efficacy and to unravel its underlying mechanistic pathways. [Display omitted] •Ginsenoside Rg1 identified as a potent HbF inducer for β-thalassemia.•Ginsenoside Rg1 boosts γ-globin and HbF expression without hindering K562 growth.•Ginsenoside Rg1 elevates γ-globin and HbF in ErPCs without affecting proliferation.•Ginsenoside Rg1 promotes erythroid differentiation similarly to HU, minus the cytotoxicity.