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

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.

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

“…3,11,33 Flavonoids like rutin and quercetin have also been favourable reported with antisickling effects via modulation of sickling active molecules (haemoglobin and 2,3-bisphophoglycerate mutase), modulation of redox homeostasis and biochemical alteration in relation to functional chemistry of sickle erythrocytes. 28,29 Again, these further confirmed the observed antisickling properties of chrysin as clearly demonstrated from our current studies.…”

“…13 These findings agree with similar studies on other flavonoids like rutin and quercetin that exhibited strong affinities to deoxy-haemoglobin and 2,3-bisphophoglycerate mutase. 28,29 By implication, this might have revealed chrysin's tendency to allosterically bind to haemoglobin with good binding affinity that may potentially alter oxygen's affinity to haemoglobin towards oxygenation due to supportive potential inhibitory effects on 2,3-bisphophoglycerate mutase by chrysin.…”

“…This is in addition to the observed decrease on the number of sickle erythrocytes upon treatment with chrysin in vitro, which was a similar observation based on other studies with rutin and quercetin. 28,29 As a sequel to the observed increase in lipid peroxidation and objectionable effects on the part of enzymatic and non-enzymatic antioxidant system vis-à-vis higher haemolysis percentage due to sickling induction, it will be practically impossible to assume that the 3D structure of membrane lipid bilayer and associated macromolecules would not be affected, including their functional chemistry. 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 or/and intracellularly.…”

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

“…The same phenomenon is described in pro-oxidant mutations, such as SCD, where accelerated denaturation of Hemoglobin S hemichrome formation and release of heme may collectively induce oxidative stress within the RBC. Antioxidant compounds have been produced in order to prevent oxidative stress presenting antisickling effects [ 7 , 8 , 42 ].…”

“…), 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 ].…”