Sickling-suppressive effects of chrysin may be associated with sequestration of deoxy-haemoglobin, 2,3-bisphosphoglycerate mutase, alteration of redox homeostasis and functional chemistry of sickle erythrocytes

Abstract

Sickle cell disease (SCD) is a medical condition caused by mutation in a single nucleotide in the β-globin gene. It is a health problem for people in sub-Saharan Africa, the Middle East and India. Orthodox drugs developed so far for SCD focus largely on symptomatic respite of pain and crisis mitigation. We investigated the antisickling effects of chrysin via modulation of deoxy-haemoglobin, 2,3-bisphosphoglycerate mutase, redox homeostasis and alteration of functional chemistry in human sickle erythrocytes. In silico and in vitro methods were adopted for the studies. Chrysin was docked against deoxy-haemoglobin and 2,3-bisphosphoglycerate mutase, with binding energies (−24.064 and −18.171 kcal/mol) and inhibition constant ( K i) of 0.990 µM and 0.993 µM at their active sites through strong hydrophobic and hydrogen bond interactions. Sickling was induced with 2% metabisulphite at 3 h. Chrysin was able to prevent sickling maximally at 2.5 µg/mL and reversed the same at 12.5 µg/mL, by 66.5% and 69.6%, respectively. Treatment with chrysin significantly ( p < 0.05) re-established the integrity of erythrocytes membrane as evident from the observed percentage of haemolysis relative to induced erythrocytes. Chrysin also significantly ( p < 0.05) prevented and reversed lipid peroxidation. Similarly, glutathione and catalase levels were observed to significantly ( p < 0.05) increase with concomitant significant ( p < 0.05) decrease in superoxide dismutase activity relative to untreated. From Fourier-transform infrared results, treatment with chrysin was able to favourably alter the functional chemistry, judging from the shifts and functional groups observed. Sickling-suppressive effects of chrysin may therefore be associated with sequestration of deoxy-haemoglobin, 2,3-bisphosphoglycerate mutase, alteration of redox homeostasis and functional chemistry of sickle erythrocytes.

Antisickling effect of chrysin is associated with modulation of oxygenated and deoxygenated haemoglobin via alteration of functional chemistry and metabolic pathways of human sickle erythrocytes

“…5 To this end, the observed alterations of the functional chemistry may potentially be related to membrane stabilizing effects of chrysin in an induced versus treated erythrocytes by virtue of the fact that erythrocytes, like other cells, are composed of lipids, proteins and carbohydrates peripherally, integral and/or intracellularly. 5…”

“…This is in addition to the observed decrease in the number of sickle erythrocytes upon treatment with chrysin in vitro , which was a similar observation based on other studies with rutin and quercetin. 5 To this end, the observed alterations of the functional chemistry may potentially be related to membrane stabilizing effects of chrysin in an induced versus treated erythrocytes by virtue of the fact that erythrocytes, like other cells, are composed of lipids, proteins and carbohydrates peripherally, integral and/or intracellularly. 5…”

“…Each well was then filled with the washing solution, put aside for 1 min after which the liquid was drained again. This was repeated for five 5 times. For color development, 50 µl chromogen solution A was added to each well, followed by 50 µl chromogen solution B.…”

“…Our research group previously demonstrated the potential of chrysin to suppress erythrocyte sickling using in silico and in vitro approaches. 5 However, the mechanism of this antisickling effects is yet to be elucidated. The present study aims at investigating this potential and unveiling the mechanism of action of this compound not only in preventing the sickling of erythrocytes but also in reversing the anomaly during crisis.…”

Oxidation of Erythrocytes Enhance the Production of Reactive Species in the Presence of Artemisinins

“…), thereby suppressing this auto-catalytic expansion of free iron, allowing them to circulate for 120 days before oxidative stress begins to promote their demise. In the case of hemoglobinopathies, antioxidant compounds were reported as a therapeutic strategy [ 6 , 7 , 8 ].…”