The role of molecular modelling strategies in validating the effects of chrysin on sodium arsenite-induced chromosomal and DNA damage

Abstract

Chrysin (CHR) is a food-based bioactive ingredient whereas, sodium arsenite (SA) is one of the major contaminant in drinking water. When ingested, SA contributes to tissue damage due to bioactivation by S-adenosyl methionine (SAM)-dependent methyltransferase. Hence, the needs to nullify this effect by investigating the potentials of CHR on SA-induced genotoxicity in rats. The experiment was divided into two successive stages (ameliorative and preventive, curative studies) for 1 week. Rats were divided into four groups: distilled water, 10mg/kg SA, 10mg/kg CHR and co-administration. In stage 2, the experimental groups were given either CHR or SA for 1 week, and treated in reversed order for additional week. Lipid peroxidation, protein carbonyl and DNA fragmentation in liver, blood brain and bone marrow cells micronucleus were assayed for using standard protocols. Molecular docking of SAM-dependent methyltransferase in the presence of CHR was conducted. CHR significantly ( p < 0.05) decreased the level of lipid peroxidation, protein carbonyls and DNA fragmentation in blood, liver and brain tissues as against group treated with SA. It also significantly ( p<0.05) reduced the level of micronuclei generated in bone marrow cells. The effects of CHR were shown to be ameliorative, preventive and curative in nature. Furthermore, CHR was able to dock (with binding energy of -24.81 kcal/mol and predicted inhibition kinetic constant (Ki) of 0.959 µM) into the active site of SAM-dependent methyltransferase with strong hydrogen bond and hydrophobic interactions. The study might have unravelled the potentials of CHR against SA-induced chromosomal and DNA damage, which might be due to inhibition of SAM-dependent methyltransferase.

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

“…This can be scientifically supported from the facts obtained from our previous study that chrysin indeed had a strong affinity to proteins based on hydrophobic and hydrophilic interactions. 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.…”

“…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. Chrysin has also been reported to have a high bioavailability which enhances its antioxidant effects by virtue of the observed decrease in lipid peroxidation with a concomitant increase in GSH, CAT and SOD, 13,14,31,32 anti-inflammatory and protein stability effects which could be advantageous in combating SCD-associated oxidative stress, inflammation and decreased HbS stability. 14 These may as well mitigate and possibly converse painful vaso-occlusive episodes characterized by endothelial dysfunction and activation of the inflammatory and coagulation pathway recently reported in SCD.…”

“…12 In recent studies from our research laboratory, the antioxidant, anticlastogenic and DNA-protective properties of chrysin were conveyed at in vitro and in vivo levels. 13 Chrysin is reported to have a high bioavailability which enhances its anti-inflammatory and protein stability effects that could be beneficial to SCD-associated oxidative stress, inflammation and decreased HbS stability. 14 Chrysin has also been reported to have enzyme inhibitory effects 15,16 but has not yet been studied on sickling-suppressive effects, thus necessitating this study.…”

Sickling-preventive effects of rutin is associated with modulation of deoxygenated haemoglobin, 2,3-bisphosphoglycerate mutase, redox status and alteration of functional chemistry in sickle erythrocytes

“…Thus, targeting these proteins as clearly discovered from our in-silico studies might provide a viable strategy in combating and managing SCD in addition to offering a sign on the possible antisickling effects of rutin. This can be rationally supported based on the results from our previous study that flavonoids undoubtedly had a strong attraction to proteins via hydrophobic and hydrophilic interactions (Babangida et al., 2018). By implication, this might have exposed rutin's predisposition to allosterically bind to haemoglobin leading to possible adjustments on oxygen's affinity to haemoglobin thereby increasing cooperativity, favouring oxygenation buttressed by the observed sequestrating effects on 2,3-bisphophoglycerate mutase.…”

Nutraceuticals in the Treatment of Pulmonary Arterial Hypertension

“…The major natural sources of this flavonoid include passion fruit, honey, and propolis [ 184 ]. In the forest, honey may contain up to 5.3 mg/kg chrysin [ 185 ]. Currently, there are no reports on factors such as temperature or cooking methods that affect the content of chrysin in propolis (28 g/l), Passiflora edulis (0.012–0.120 mg/ml), molasses (5.3 mg/kg), or forest honey (0.10 mg/kg) [ 186 ].…”