Monodora myristica(African nutmeg) modulates redox homeostasis and alters functional chemistry in sickled erythrocytes

Abstract

The antioxidative effect of Monodora myristica seed acetone extract and its effect on chemical functional groups were investigated in sickled erythrocytes as well as molecular modeling of the antisickling potentials of its secondary metabolites. The extract was subjected to gas chromatography-mass spectrometry to identify the compounds present, which were then docked into the allosteric-binding site of deoxy-hemoglobin. The extract was incubated with sickled erythrocytes at 37°C for 6, 12, and 24 h and were subjected to antioxidative analysis for reduced glutathione (GSH), superoxide dismutase (SOD), catalase, and lipid peroxidation (LPO). Chemical functional group of the treated cells was analyzed via Fourier transform infrared spectroscopy (FTIR). The predominant compounds identified were 17-octadecynoic acid; oleic acid, androstan-3-one, 17-hydroxy-2-methyl- (2.beta.,5.beta.,17.beta.)-; estran-3-one, 17-(acetyloxy)-2-methyl-, (2.alpha., 5.alpha., 17.beta.), and (+)-3-carene, 10-(acetylmethyl)-. They all fitted well within the active site of Hb with good binding affinity, as evidenced by the negative CDocker interaction energies of their complexes ranging between -54.4 and -26.7 kcal/mol. Treatment with the extract exacerbated SOD and catalase activities as well as GSH level, while LPO was suppressed. This antioxidative activity was time and/or dose dependent, with 6 and 12 h incubation showing the optimum activity. FTIR analysis of the treated cells showed the presence of hydrophobic functional groups. The synergetic molecular interaction of the major compounds of the extract with the α-dimer of Hb depicts an antisickling effect of M. myristica acetone extract. This is accompanied by exacerbation of endogenous antioxidant enzymes activity and modification of the functional chemistry of the cells.

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.

“…Sickle cell disease (SCD) remains a major inherited hemoglobinopathy amongst Africans, with sub-Saharan Africa among the most affected (Erukainure et al, 2017). It is an inherently inbred ailment in which the "SS" individual possesses a nonconforming beta globin gene.…”

“…Corroborating our docking results, pre and post-treatment with quercetin decreased the number of sickle erythrocytes suggesting a protective and curative role of quercetin against sickling of erythrocytes. This is possible because, the sickling process in SCD patients is characterized by continuous polymerization of erythrocytes due to oxidative stress in addition to inadequate oxygen supply typical of sickle erythrocytes (Erukainure et al, 2017;Ngozi, 2013;Poillon et al, 1995). The antioxidant properties of quercetin can protect against oxidative stress that further contribute to the stability of sickle erythrocyte membranes (Zheng et al, 2017).…”

“…The best concentrations (5.0µg/mL for preventive and 7.5µg/mL for curative studies) with highest antisickling percentage were incubated with 100 µL sickle erythrocyte for 3 hours at 370C as previously explicated in the above section, while adopting the methods as explained elsewhere (Erukainure et al, 2017). When treated, the samples were dehydrated under pressure and sandwiched between potassium bromide.…”

Phaseolus lunatus(lima beans) abates Fe2+‐induced hepatic redox imbalance; inhibits intestinal glucose absorption and major carbohydrate catabolic enzymes; and modulates muscle glucose uptake

“…Abundant levels of SOD and catalase levels have been reported in hepatic tissues (Davari, Talaei, & Alaei, ). SOD catalyzes the dismutation of O 2 − to H 2 O 2 , which is then converted to O 2 and H 2 O (Erukainure, Ajiboye et al, ). Thus, their depleted activities in the hepatic tissue on incubation with FeSO 4 depict an incidence of oxidative hepatic injury (Figure b,c).…”

“…The inhibitory effect of the extract on glucose‐6‐phosphatase activity was determined in hepatic tissue homogenates ex vivo (as described in ex vivo antioxidative activity) using the methods of Mahato, Bhattacharya, and Shanthi (), and Zhang et al () as modified by Erukainure, Mopuri et al ().…”