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eCAM Advance Access published online on December 11, 2007
eCAM, doi:10.1093/ecam/nem139
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© 2007 The Author(s).
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Fetal Hemoglobin Inducers from the Natural World: A Novel Approach for Identification of Drugs for the Treatment of β-Thalassemia and Sickle-Cell Anemia

Nicoletta Bianchi1,2, Cristina Zuccato1, Ilaria Lampronti1,2, Monica Borgatti1 and Roberto Gambari1,2

1ER-GenTech, Department of Biochemistry and Molecular Biology, Section of Molecular Biology, University of Ferrara 2GenTech-for-Thal, Laboratory for the Development of Pharmacological and Pharmacogenomic Therapy of Thalassaemia, Biotechnology Centre, Ferrara, Italy

The objective of this review is to present examples of lead compounds identified from biological material (fungi, plant extracts and agro-industry material) and of possible interest in the field of a pharmacological approach to the therapy of β-thalassemia using molecules able to stimulate production of fetal hemoglobin (HbF) in adults. Concerning the employment of HbF inducers as potential drugs for pharmacological treatment of β-thalassemia, the following conclusions can be reached: (i) this therapeutic approach is reasonable, on the basis of the clinical parameters exhibited by hereditary persistence of fetal hemoglobin patients, (ii) clinical trials (even if still limited) employing HbF inducers were effective in ameliorating the symptoms of β-thalassemia patients, (iii) good correlation of in vivo and in vitro results of HbF synthesis and {gamma}-globin mRNA accumulation indicates that in vitro testing might be predictive of in vivo responses and (iv) combined use of different inducers might be useful to maximize HbF, both in vitro and in vivo. In this review, we present three examples of HbF inducers from the natural world: (i) angelicin and linear psoralens, contained in plant extracts from Angelica arcangelica and Aegle marmelos, (ii) resveratrol, a polyphenol found in grapes and several plant extracts and (iii) rapamycin, isolated from Streptomyces hygroscopicus.

Keywords: fetal hemoglobin – β-thalassemia – rapamycin – medicinal plants – resveratrol – red wine – psoralens

For reprints and all correspondence: Prof. Roberto Gambari, GenTech-for-Thal, Laboratory for the Development of Pharmacological and Pharmacogenomic Therapy of Thalassaemia, Biotechnology Centre, Ferrara, Italy. Tel: +39 0532 974443; Fax: +39 0532 974500; E-mail: gam{at}unife.it

Received June 14, 2007; accepted August 23, 2007


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