Background The devastating public health impact of malaria has prompted the need for effective interventions. Malaria control gained traction after the introduction of artemisinin-based combination therapy (ACT). However, the emergence of artemisinin (ART) partial resistance in Southeast Asia and emerging reports of delayed parasite sensitivity to ACT in African parasites signal a gradual trend towards treatment failure. Monitoring the prevalence of mutations associated with artemisinin resistance in African populations is necessary to stop resistance in its tracks. Mutations in Plasmodium falciparum genes pfk13, pfcoronin and pfatpase6 have been linked with ART partial resistance. Methods Findings from published research articles on the prevalence of pfk13, pfcoronin and pfatpase6 polymorphisms in Africa were collated. PubMed, Embase and Google Scholar were searched for relevant articles reporting polymorphisms in these genes across Africa from 2014 to August 2021, for pfk13 and pfcoronin. For pfatpase6, relevant articles between 2003 and August 2021 were retrieved. Results Eighty-seven studies passed the inclusion criteria for this analysis and reported 742 single nucleotide polymorphisms in 37,864 P. falciparum isolates from 29 African countries. Five validated-pfk13 partial resistance markers were identified in Africa: R561H in Rwanda and Tanzania, M476I in Tanzania, F446I in Mali, C580Y in Ghana, and P553L in an Angolan isolate. In Tanzania, three (L263E, E431K, S769N) of the four mutations (L263E, E431K, A623E, S769N) in pfatpase6 gene associated with high in vitro IC50 were reported. pfcoronin polymorphisms were reported in Senegal, Gabon, Ghana, Kenya, and Congo, with P76S being the most prevalent mutation. Conclusions This meta-analysis provides an overview of the prevalence and widespread distribution of pfk13, pfcoronin and pfatpase6 mutations in Africa. Understanding the phenotypic consequences of these mutations can provide information on the efficacy status of artemisinin-based treatment of malaria across the continent. Graphical Abstract

This study was done to investigate the effects of common food additives such as sodium benzoate (SB) and ascorbic acid (AA) on haematological parameters of male Wistar rats. Forty-eight (48) male albino rats with an average weight of 105 g were grouped into twelve (n = 4) of Basal Control and other 11 groups orally administered 1 mg of SB, 10 mg of SB, 10 mg of AA, 0.2 mg of AA + 0.5 mg of SB, 0.2 mg of AA + 1 mg of SB, 0.2 mg of AA + 10 mg of SB, 0.2 mg of SB + 0.1 mg of AA, 0.2 mg of SB + 0.5 mg of AA, carbonated soft drinks (CSD)+ 0.1 mg of AA, CSD + 1 mg of AA and CSD + 10 mg of AA, respectively for 21 non-consecutive days. At the end of the experiment, blood samples were collected in EDTA anticoagulant tubes, haematological parameters were evaluated, and data were analyzed. There was a dose-dependent increase (p < 0.05) in White Blood Cell counts of SB treated rats compared with the control group. The lymphocyte exhibited significant reduction (p < 0.05) in the groups treated with 1mg SB and 10mg SB/kg bodyweight of 67 ± 2.96 and 58 ± 4.18%, respectively. The mean corpuscular haemoglobin showed no significant difference at 95% confidence interval. However, mean corpuscular haemoglobin concentration, haematocrit and platelet were affected by an increase in the concentrations of SB. High SB concentrations increased the destruction of erythrocytes, which directly increased the catabolism of haemoglobin. However, AA administration mitigated the adverse effects of SB on the haematological parameters of the animal.

Antimalarial drug resistance has thrown a spanner in the works of malaria elimination. New drugs are required for ancillary support of existing malaria control efforts. Plasmodium falciparum requires host glucose for survival and proliferation. On this basis, P. falciparum hexose transporter 1 (PfHT1) protein involved in hexose permeation is considered a potential drug target. In this study, we tested the antimalarial activity of some compounds against PfHT1 using computational techniques. We performed high throughput virtual screening of 21,352 small-molecule compounds against PfHT1. The stability of the lead compound complexes was evaluated via molecular dynamics (MD) simulation for 100 nanoseconds. We also investigated the pharmacodynamic, pharmacokinetic and physiological characteristics of the compounds in accordance with Lipinksi rules for drug-likeness to bind and inhibit PfHT1. Molecular docking and free binding energy analyses were carried out using Molecular Mechanics with Generalized Born and Surface Area (MMGBSA) solvation to determine the selectivity of the hit compounds for PfHT1 over the human glucose transporter (hGLUT1) orthologue. Five important PfHT1 inhibitors were identified: Hyperoside (CID5281643); avicularin (CID5490064); sylibin (CID5213); harpagoside (CID5481542) and quercetagetin (CID5281680). The compounds formed intermolecular interaction with the binding pocket of the PfHT1 target via conserved amino acid residues (Val314, Gly183, Thr49, Asn52, Gly183, Ser315, Ser317, and Asn48). The MMGBSA analysis of the complexes yielded high free binding energies. Four (CID5281643, CID5490064, CID5213, and CID5481542) of the identified compounds were found to be stable within the PfHT1 binding pocket throughout the 100 nanoseconds simulation run time. The four compounds demonstrated higher affinity for PfHT1 than the human major glucose transporter (hGLUT1). This investigation demonstrates the inhibition potential of sylibin, hyperoside, harpagoside, and avicularin against PfHT1 receptor. Robust preclinical investigations are required to validate the chemotherapeutic properties of the identified compounds.

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Aim: This study aimed to investigate the antiplasmodial activity and effect of stem bark of Terminalia avicennioides made as dietary feed fed to mice infected with Plasmodium berghei, on some serum biochemistry. Methodology: Twenty (20) mice were divided into four groups. Group 1 was not infected with Plasmodium berghei (normal control), Group 2 was infected with P. berghei but not treated (negative control). Group 3 was infected and treated with 5.0 mg/kg of Arthemeter-Lumefantrine (positive control). Groups 4 was infected and fed with treated feed (T. avicennioides). Treatments were carried out for five days. Blood was taken daily from the tail of the mice before treatment for the assessment of parasitaemia. The animals were sacrificed on the fifth day and the whole blood was collected into EDTA bottle. Serum obtained was used to assay for biochemical parameters. Results: Parasitaemia count was significantly lower (p<0.05) in all the treated groups when compared with the negative control group. The high-density lipoprotein was significantly higher (P<0.05) in the normal control (123.14±3.19) when compared with the positive control (99.18±2.76), negative control (85.29±0.85) and the group treated with T avicennioides (86.14±3.21). The serum alanine aminotransferase, alkaline phosphatase and aspartate aminotransferase level in the group treated with T. avicennioides (167.90±4.13, 15.87±1.32 and 17.50±1.95) respectively were significantly reduced (p<0.05) when compared with the negative control (197.25±5.44, 20.01±1.32 and 26.71±0.45) respectively. The mean bilirubin and albumin level in the negative control showed no significant difference when compared with the group fed with T. avicennioides. Conclusion: The study concluded that T. avicennioides have antiplasmodial activity with a mild adverse effect on liver function.

Sodium benzoate and ascorbic acid are the most significant additives in carbonated soft drink. The effect of consuming these additives singly and simultaneous consumption of carbonated soft drink with ascorbic acid were investigated to understand histopathological alterations in both liver cells and testis. Expermental mice were grouped into 7 different sets and five of the groups were adminstered 4 mg/kg body weight of the treatments, while the other two groups served as normal and vehicle control. The histological results reveal presence of activated Kupffer cells, sinusoidal widening and cytoplasmic vacuolation in the liver of mice exposed to carbonated soft drink, sodium benzoate and sodium benzoate with ascorbic acid, while in addition to these, there were severe Femi-Oloye et al.; IJBCRR, 26(4): 1-9, 2019; Article no.IJBCRR.46376 2 cellular and granular casts in group administered carbonated soft drink with ascorbic acid. Severe cellular casts and granular cast is an indication of hepatic diseases. Carbonated soft drink, sodium benzoate, ascorbic acid and sodium benzoate with ascorbic acid did not alter the histopathology of the testis, but simultaneous consumption of carbonated soft drink with ascorbic acid might prevent the formation of new stem cells and may hinder them from dividing to specialized cells. Original Research Article

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Malaria chemotherapy has been plagued by parasite resistance. Novel drugs must be continually explored for malaria treatment. Plasmodium falciparum requires host glucose for survival and proliferation. Protein involved in hexose permeation, P. falciparum hexose transporter 1 (PfHT1) is a potential drug target. We performed high throughput virtual screening of 21,352 small-molecule compounds against PfHT1. The stability of the lead compound complexes was evaluated via molecular dynamics (MD) simulation for 100 nanoseconds. We also investigated the pharmacodynamic, pharmacokinetic and physiological characteristics of the compounds in accordance with Lipinksi rules for drug-likeness to bind and inhibit PfHT1. Molecular docking and free binding energy analyses were carried out using Molecular Mechanics with Generalised Born and Surface Area (MMGBSA) solvation to determine the selectivity of the hit compounds for PfHT1 over the human glucose transporter (hGLUT1) orthologue. Five important compounds were identified: Hyperoside (CID5281643); avicularin (CID5490064); sylibin (CID5213); harpagoside (CID5481542) and quercetagetin (CID5281680). The compounds formed intermolecular interaction with the binding pocket of the target via conserved amino acid residues (Val314, Gly183, Thr49, Asn52, Gly183, Ser315, Ser317, and Asn48). The MMGBSA analysis of the complexes yielded high free binding energies. Four (CID5281643, CID5490064, CID5213, and CID5481542) of the identified compounds were found to be stable within the PfHT1 binding pocket throughout the 100 nanoseconds simulation run time. The four compounds demonstrated higher affinity for PfHT1 than the human major glucose transporter (hGLUT1). This investigation demonstrates the inhibition potential of sylibin, hyperoside, harpagoside, and avicularin against PfHT1 receptor. Robust preclinical investigations are required to validate the chemotherapeutic properties of the identified compounds.