A reduced curcuminoid analog as a novel inducer of fetal hemoglobin.

Thalassemia is an inherited disorder of hemoglobin molecules that is characterized by an imbalance of α- and ß-globin chain synthesis. Accumulation of unbound α-globin chains in erythroid cells is the major cause of pathology in ß-thalassemia. Stimulation of γ-globin production can ameliorate disease severity as it combines with the α-globin to form fetal hemoglobin. We examined γ-globin-inducing effect of curcuminoids extracted from Curcuma longa L. and their metabolite reduced forms in erythroid leukemia K562 and human primary erythroid precursor cells. The results showed that curcuminoid compounds, especially bisdemethoxycurcumin are potential γ-globin enhancers. We also demonstrated that its reduced analog, hexahydrobisdemethoxycurcumin (HHBDMC), is most effective and leads to induction of γ-globin mRNA and HbF in primary erythroid precursor cells for 3.6 ± 0.4- and 2.0 ± 0.4-folds, respectively. This suggested that HHBDMC is the potential agent to be developed as a new therapeutic drug for ß-thalassemia and related ß-hemoglobinopathies.

Labdane diterpenes from the aerial parts of Curcuma comosa enhance fetal hemoglobin production in an erythroid cell line.

Three new labdane diterpenes, curcucomosins A-C (1-3), four known labdane diterpenes, 4-7, and a known diarylheptanoid, 8, were isolated from the aerial parts of Curcuma comosa. The structures of the new diterpenes were elucidated by spectroscopic data analysis. The fetal hemoglobin (Hb F) induction potency of the isolated compounds was examined using a K562 reporter cell line harboring the enhanced green fluorescence protein (EGFP) gene under the control of a (G)gamma-globin promoter. Compound 6, isocoronarin D, exhibited the highest Hb F induction effect of 1.6-fold at 20 microM.