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.

Abstract

Abstract 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.