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

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 Effects of Quercetin may be Associated with Modulation of Deoxyhaemoglobin, 2, 3-bisphosphoglycerate mutase, Redox Homeostasis and Alteration of Functional Chemistry in Human Sickle Erythrocytes.

It is now glaring that sickle cell anaemia is still one of the highest leading inbred hemoglobinopathy amongst Africans. This study examined the antisickling effects of quercetin via modulation of deoxy-haemoglobin, redox homeostasis and alteration of functional chemistry in human sickle erythrocyte using in silico and in vitro models while espousing preventive and curative approaches. Quercetin was docked against deoxy-haemoglobin and 2, 3-bisphosphoglycerate mutase, with binding energies (−30.427 and −21.106 kcal/mol) and Ki of 0.988μM and 0.992μM at their catalytic sites via strong hydrophobic and hydrogen bond interactions. Induction of sickling was done using 2% metabisulphite at 3h. Treatment with quercetin prevented sickling outstandingly at 5.0μg/mL and reversed same at 7.5μg/mL, 83.6% and 75.9%, respectively. Quercetin also significantly (P<0.05) maintained the integrity of erythrocyte membrane apparently from the observed % haemolysis relative to untreated. Quercetin significantly (P<0.05) prevented and counteracted lipid peroxidation while stimulating GSH and CAT levels which were detected to considerably (P<0.05) increase with simultaneous significant (P<0.05) reduction in SOD level based on curative approach. Umpiring from our FTIR results, a favorable alteration in the part of functional chemistry in terms of shifts (bend and stretches) and functional groups were observed relative to the induced erythrocyte/untreated. Thus, antisickling effects of quercetin may be associated with modulation of deoxy-haemoglobin, redox homeostasis and alteration of functional chemistry in human sickle erythrocytes.