A reduced curcuminoid analog as a novel inducer of fetal hemoglobin
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ORIGINAL ARTICLE
A reduced curcuminoid analog as a novel inducer of fetal hemoglobin Nattawara Chaneiam & Chatchawan Changtam & Thongperm Mungkongdee & Umaporn Suthatvoravut & Pranee Winichagoon & Jim Vadolas & Apichart Suksamrarn & Suthat Fucharoen & Saovaros Svasti
Received: 11 May 2012 / Accepted: 7 October 2012 / Published online: 19 October 2012 # Springer-Verlag Berlin Heidelberg 2012
Abstract Thalassemia is an inherited disorder of hemoglobin molecules that is characterized by an imbalance of α- and βglobin chain synthesis. Accumulation of unbound α-globin chains in erythroid cells is the major cause of pathology in βthalassemia. 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 γglobin 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±0.4folds, respectively. This suggested that HHBDMC is the potential agent to be developed as a new therapeutic drug for βthalassemia and related β-hemoglobinopathies.
Keywords Hemoglobin F . Thalassemia . Curcumin . Reduced curcuminoid analog Abbreviations Hb Hemoglobin BDMC Bisdemethoxycurcumin THBDMC Tetrahydrobisdemethoxycurcumin HHBDMC Hexahydrobisdemethoxycurcumin OHBDMC Octahydrobisdemethoxycurcumin
Introduction β-Thalassemia is an inherited disorder of hemoglobin synthesis characterized by the absence or reduction of β-globin chains in erythroid cells [1, 2]. The continued synthesis of α-globin chains, in normal amount, leads to excess αglobins, which do not bind with β-globins and accumulate
Electronic supplementary material The online version of this article (doi:10.1007/s00277-012-1604-1) contains supplementary material, which is available to authorized users. N. Chaneiam Institute of Nutrition, Mahidol University, Nakhonpathom 73170, Thailand N. Chaneiam : T. Mungkongdee : P. Winichagoon : S. Fucharoen : S. Svasti Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Nakhonpathom 73170, Thailand C. Changtam : A. Suksamrarn Department of Chemistry and Center for Innovation in Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok 10240, Thailand
U. Suthatvoravut Department of Pediatric, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand J. Vadolas CAGT Research Group, The Murdoch Childrens Research Institute, Royal Children’s Hospital, Melbourne, VIC 3052, Australia S. Svasti (*) Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand e-mail: [email protected]
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within erythroid precursors and mature red blood cells.
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