Natural Remedies for the Treatment of Beta-Thalassemia and Sickle Cell Anemia—Current Status and Perspectives in Fetal Hemoglobin Reactivation

Table 1

Classification of HbF inducers.

Category	Examples of Inducers	Mechanism of action
Chemotherapeutic agents (ribonucleotide reductase inhibitors)	HU	Inhibition of DNA analysis [13, 47]
Chemotherapeutic agents (DNA methyltransferase inhibitors)	5-Azacytidine, decitabine and citarabine	Hypomethylation of DNA [13, 47]
Short chain fatty acids and derivatives (histone deacetylase inhibitors)	Butyrates, tricostatin, apicidine, and scriptaid	Inhibition of histone deacetylase (HDAC) activity (applicable to some SCFAs only) [47, 56–65]
DNA binding agents	Mithramycin, cisplatin and analogues, tallimustine and analogues, and angelicin	DNA-binding activity [5, 50]
mTOR inhibitors	Rapamycin	FRAP-mTOR signal transduction targeting [49]
Immunomodulatory drugs	Thalidomide, revlimid, and Pomalidomide	Histone acetylation at γ-globin gene promoter [5, 66]
Cytokines	Erythropoietin (EPO), stem cell factor and TGF-β	Increase in the frequency of erythroid progenitors programmed to hemoglobin F [5, 47, 52, 53, 67, 68]