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 β-globin chain synthesis. Accumulation of unbound α-globin chains in erythroid cells is the major cause of pathology in β-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 β-thalassemia and related β-hemoglobinopathies.
Institute of Nutrition, Mahidol University, Nakhonpathom, 73170, Thailand.
Nattawara
N
Chaneiam
Chatchawan
C
Changtam
Thongperm
T
Mungkongdee
Umaporn
U
Suthatvoravut
Pranee
P
Winichagoon
Jim
J
Vadolas
Apichart
A
Suksamrarn
Suthat
S
Fucharoen
Saovaros
S
Svasti
D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003474:Curcumin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D036381:Diarylheptanoids; D041905:Erythroid Cells / Q000187:drug effects / Q000378:metabolism; D005319:Fetal Hemoglobin / Q000819:agonists / Q000096:biosynthesis*; D006801:Humans; D020014:K562 Cells; D055545:gamma-Globins / Q000819:agonists / Q000096:biosynthesis
D036381:Diarylheptanoids; D055545:gamma-Globins; C034786:bisdemethoxycurcumin; D005319:Fetal Hemoglobin; D003474:Curcumin; C050229:demethoxycurcumin