Induction of foetal haemoglobin synthesis in erythroid progenitor stem cells: mediated by water‐soluble components of Terminalia catappa

Abstract

Current novel therapeutic agents for the treatment of sickle cell anaemia (SCA) focus on increasing foetal haemoglobin (HbF) levels in SCA patients. Unfortunately, the only approved HbF-inducing agent, hydroxyurea, has long-term unpredictable side effects. Studies have shown the potential of plant compounds to modulate HbF synthesis in primary erythroid progenitor stem cells. We isolated a novel HbF-inducing Terminalia catappa distilled water active fraction (TCDWF) from Terminalia catappa leaves that induced the commitment of erythroid progenitor stem cells to the erythroid lineage and relatively higher HbF synthesis of 9.2- and 6.8-fold increases in both erythropoietin (EPO)-independent and EPO-dependent progenitor stem cells respectively. TCDWF was differentially cytotoxic to EPO-dependent and EPO-independent erythroid progenitor stem cell cultures as revealed by lactate dehydrogenase release from the cells. TCDWF demonstrated a protective effect on EPO-dependent and not EPO-independent progenitor cells. TCDWF induced a modest increase in caspase 3 activity in EPO-independent erythroid progenitor stem cell cultures compared with a significantly higher (P˂0.05) caspase 3 activity in EPO-dependent ones. The results demonstrate that TCDWF may hold promising HbF-inducing compounds, which work synergistically, and suggest a dual modulatory effect on erythropoiesis inherent in this active fraction.

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

“…Recently, it is reported that an Indian almond, called Terminalia catappa , has long been used as a traditional herbal treatment for SCA in Nigeria [ 78 ]. Aimola et al has then demonstrated Terminalia catappa distilled water active fraction (TCDWF) from Terminalia catappa leaves exhibit a stimulatory effect on the HbF production in primary erythroid prohenitor stem cells (EPSCs) [ 77 ]. Terminalia catappa consists of flavonoids, alkaloids, and anthraquinones.…”

“…Terminalia catappa consists of flavonoids, alkaloids, and anthraquinones. Also, through gas chromatography-mass spectrometry (GCMS), it is shown that a group of highly related long-chain fatty acids, for example, hexadecanoic acid, 10-octadecenoic acid, and octadecenoic acid, are present in the TCDWF [ 77 ]. Yet, further investigation is required in order to confirm the biological activities of these active compounds present in the TCDWF.…”

An updated review of Terminalia catappa

“…Aimola et al [10] isolated a novel fetal hemoglobin-inducing compound ( T. catappa distilled water active fraction) from the leaves of T. catappa , which work synergistically, and recommended a dual modulatory effect on inherent erythropoiesis. Ratnasooriya et al [11] found that the extract form of tender leaves have anti-inflammatory as well as analgesic activities without affecting the estrous cycle, and also found that dosage does not induce sedation.…”

Cis-vaccenic acid induces differentiation and up-regulates gamma globin synthesis in K562, JK1 and transgenic mice erythroid progenitor stem cells

“…Increase in RBC membrane CVA content has been shown to protect humans against coronary heart disease (Djoussé et al, 2012), However, very little is known about the link between CVA metabolism and hemoglobin expression. We have previously reported the fetal hemoglobin inducing activity of a water purified fraction of Terminalia catappa leaf extract on primary hematopoietic progenitor cells (Aimola et al, 2014). Further chromatographic studies on this fraction revealed that this fraction contained CVA (un-published data).…”