Revisiting fetal hemoglobin inducers in beta-hemoglobinopathies: a review of natural products, conventional and combinatorial therapies

Mukherjee, Mandrita; Rahaman, Motiur; Ray, Suman; Shukla, Praphulla Chandra; Dolai, Tuphan Kanti; Chakravorty, Nishant

doi:10.1007/s11033-021-06977-8

Cited by 10 publications

(7 citation statements)

References 114 publications

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“…These data confirm the already-reported effects of these Cinchona alkaloids on the K562 cell system [28]. The induction of K562 differentiation was found to be associated, as expected, with the inhibition of cell proliferation, as reported in the K562 cell system for several other HbF inducers, such as hydroxyurea, mithramycin, rapamycin, cisplatin analogues and trimethylangelicin [25][26][27]37,[56][57][58][59]. This effect of cinchonidine, quinidine and cinchonine on K562 cell proliferation is presented and comparatively analyzed in Supplementary Figures S1 and S2.…”

Section: Cinchonidine Quinidine and Cinchonine Induce Differentiation...supporting

confidence: 91%

“…Accordingly, the validation of the clinical relevance of already-known HbF inducers and the characterization of novel HbF inducers are still projects of great interest [24][25][26][27]. In this context, a paper was recently published by Iftikhar et al on the effects of Cinchona alkaloids (cinchonidine and quinidine) as natural fetal hemoglobin-inducing agents in human erythroleukemia cells [28].…”

Section: Discussionmentioning

confidence: 99%

“…Accordingly, the validation of clinical relevance of already known HbF inducers and the characterization of novel HbF inducers are still projects of great interest [24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

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Treatment of Erythroid Precursor Cells from β-Thalassemia Patients with Cinchona Alkaloids: Induction of Fetal Hemoglobin Production

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Zurlo

et al. 2021

IJMS

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β-thalassemias are among the most common inherited hemoglobinopathies worldwide and are the result of autosomal mutations in the gene encoding β-globin, causing an absence or low-level production of adult hemoglobin (HbA). Induction of fetal hemoglobin (HbF) is considered to be of key importance for the development of therapeutic protocols for β-thalassemia and novel HbF inducers need to be proposed for pre-clinical development. The main purpose on this study was to analyze Cinchona alkaloids (cinchonidine, quinidine and cinchonine) as natural HbF-inducing agents in human erythroid cells. The analytical methods employed were Reverse Transcription quantitative real-time PCR (RT-qPCR) (for quantification of γ-globin mRNA) and High Performance Liquid Chromatography (HPLC) (for analysis of the hemoglobin pattern). After an initial analysis using the K562 cell line as an experimental model system, showing induction of hemoglobin and γ-globin mRNA, we verified whether the two more active compounds, cinchonidine and quinidine, were able to induce HbF in erythroid progenitor cells isolated from β-thalassemia patients. The data obtained demonstrate that cinchonidine and quinidine are potent inducers of γ-globin mRNA and HbF in erythroid progenitor cells isolated from nine β-thalassemia patients. In addition, both compounds were found to synergize with the HbF inducer sirolimus for maximal production of HbF. The data obtained strongly indicate that these compounds deserve consideration in the development of pre-clinical approaches for therapeutic protocols of β-thalassemia.

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Section: Cinchonidine Quinidine and Cinchonine Induce Differentiation...supporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

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Treatment of Erythroid Precursor Cells from β-Thalassemia Patients with Cinchona Alkaloids: Induction of Fetal Hemoglobin Production

Zuccato

Cosenza

Zurlo

et al. 2021

IJMS

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“…Another positive effect of resveratrol on fetal outcomes is its ability to increase fetal hemoglobin levels (HbF) [208]. Among the hemoglobinopathies, beta-thalassemia is characterized by a reduced synthesis of the beta-globin chain, with an unbalanced production of the globin chain, ineffective erythropoiesis, and anemia.…”

Section: Fetus and Resveratrolmentioning

confidence: 99%

Effect of Resveratrol on Pregnancy, Prenatal Complications and Pregnancy-Associated Structure Alterations

et al. 2023

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Adverse pregnancy outcomes are considered significant health risks for pregnant women and their offspring during pregnancy and throughout their lifespan. These outcomes lead to a perturbated in-utero environment that impacts critical phases of the fetus’s life and correlates to an increased risk of chronic pathological conditions, such as diabetes, obesity, and cardiovascular diseases, in both the mother's and adult offspring’s life. The dietary intake of naturally occurring antioxidants promotes health benefits and disease prevention. In this regard, maternal dietary intake of polyphenolic antioxidants is linked to a reduced risk of maternal obesity and cardio-metabolic disorders, positively affecting both the fetus and offspring. In this work, we will gather and critically appraise the current literature highlighting the effect/s of the naturally occurring polyphenol antioxidant resveratrol on oxidative stress, inflammation, and other molecular and physiological phenomena associated with pregnancy and pregnancy conditions, such as gestational diabetes, preeclampsia, and preterm labor. The resveratrol impact on prenatal complications and pregnancy-associated structures, such as the fetus and placenta, will also be discussed. Finally, we will draw conclusions from the current knowledge and provide future perspectives on potentially exploiting resveratrol as a therapeutic tool in pregnancy-associated conditions.

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“…In recent years, progress on the knowledge of molecular mechanisms involved in Hb switching, the concept of HPHF, combined with epidemiological and clinical observations has provided important evidence on the beneficial role of increasing HbF levels in ameliorating the clinical complications of β-thalassemia and SCD [17]. This can be achieved by either classic drug-modulating approaches or by gene therapy and genome-editing approaches [18][19][20][21][22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Pharmacological Induction of Fetal Hemoglobin in β-Thalassemia and Sickle Cell Disease: An Updated Perspective

et al. 2022

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A significant amount of attention has recently been devoted to the mechanisms involved in hemoglobin (Hb) switching, as it has previously been established that the induction of fetal hemoglobin (HbF) production in significant amounts can reduce the severity of the clinical course in diseases such as β-thalassemia and sickle cell disease (SCD). While the induction of HbF using lentiviral and genome-editing strategies has been made possible, they present limitations. Meanwhile, progress in the use of pharmacologic agents for HbF induction and the identification of novel HbF-inducing strategies has been made possible as a result of a better understanding of γ-globin regulation. In this review, we will provide an update on all current pharmacological inducer agents of HbF in β-thalassemia and SCD in addition to the ongoing research into other novel, and potentially therapeutic, HbF-inducing agents.

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Revisiting fetal hemoglobin inducers in beta-hemoglobinopathies: a review of natural products, conventional and combinatorial therapies

Cited by 10 publications

References 114 publications

Treatment of Erythroid Precursor Cells from β-Thalassemia Patients with Cinchona Alkaloids: Induction of Fetal Hemoglobin Production

Treatment of Erythroid Precursor Cells from β-Thalassemia Patients with Cinchona Alkaloids: Induction of Fetal Hemoglobin Production

Effect of Resveratrol on Pregnancy, Prenatal Complications and Pregnancy-Associated Structure Alterations

Pharmacological Induction of Fetal Hemoglobin in β-Thalassemia and Sickle Cell Disease: An Updated Perspective

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