Institute of Nutrition, Mahidol University, Nakhonpathom, 73170, Thailand.
Ann Hematol. 2013 Mar;92(3):379-86. doi: 10.1007/s00277-012-1604-1. Epub 2012 Oct 19.
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.
地中海贫血是一种血红蛋白分子的遗传性疾病，其特征是α-和β-球蛋白链合成失衡。未结合的α-珠蛋白链在红细胞中的积累是β-地中海贫血病理的主要原因。刺激γ-珠蛋白的产生可以改善疾病的严重程度，因为它与α-珠蛋白结合形成胎儿血红蛋白。我们研究了从姜黄中提取的姜黄素及其代谢还原形式对红细胞白血病 K562 和人原代红细胞前体细胞中γ-珠蛋白的诱导作用。结果表明，姜黄素化合物，特别是双去甲氧基姜黄素，是潜在的γ-珠蛋白增强剂。我们还表明，其还原类似物六氢双去甲氧基姜黄素（HHBDMC）最为有效，可分别诱导原代红细胞前体细胞中γ-珠蛋白 mRNA 和 HbF 的表达增加 3.6±0.4-和 2.0±0.4 倍。这表明 HHBDMC 是一种有潜力的药物，可以开发为治疗β-地中海贫血和相关β-血红蛋白病的新药。
