Blessing Oluebube Akumadu

The rising burden of Diabetes mellitus (DM) globally and particularly in sub-Sahara Africa calls for alternative treatment solutions. This is because the currently available drugs for its management are limited due to undesirable adverse effects and high cost. Thus, this review explores diabetes and summarizes its treatment options, focusing mainly on medicinal plants therapy. Information on twenty-five selected medicinal plants from sub-Sahara Africa having hypoglycemic and anti-diabetic potentials was obtained via electronic search of major databases, such as Pubmed/Medline, Scopus, Google Scholar and web of science. Predominant bioactive compounds found in these plants include tannins, carpaine, terpenoids, hexadecenoic acid, luteolin, saponins, glycosides, rutin, quercetin, vindoline and kaempferol. Robust evidence indicates that these medicinal plants and their bioactive components exert their antidiabetic potentials via different mechanisms, including: regeneration of pancreatic β-cell and insulin secretion; inhibition of α-amylase, inhibition of intestinal glucose absorption and liver glucose production; antioxidative stress; limitation of glycogen degradation and gluconeogenesis; anti-inflammatory, immunoregulatory. DM imposes a tremendous burden in the region, and its prevalence is not abating; thus the rich flora of the region with known hypoglycemic and antidiabetic efficacy could be explored as a complementary therapy in its management.

Diabetes mellitus (DM) underscores a rising epidemic orchestrating critical socio-economic burden on countries globally. Different treatment options for the management of DM are evolving rapidly because the usual methods of treatment have not completely tackled the primary causes of the disease and are laden with critical adverse effects. Thus, this narrative review explores different treatment regimens in DM management and the associated challenges. A literature search for published articles on recent advances in DM management was completed with search engines including Web of Science, Pubmed/Medline, Scopus, using keywords such as DM, management of DM, and gene therapy. Our findings indicate that substantial progress has been made in DM management with promising results using different treatment regimens, including nanotechnology, gene therapy, stem cell, medical nutrition therapy, and lifestyle modification. However, a lot of challenges have been encountered using these techniques, including their optimization to ensure optimal glycemic, lipid, and blood pressure modulation to minimize complications, improvement of patients’ compliance to lifestyle and pharmacologic interventions, safety, ethical issues, as well as an effective delivery system among others. In conclusion, lifestyle management alongside pharmacological approaches and the optimization of these techniques is critical for an effective and safe clinical treatment plan.

Caseinolytic proteins (Clp), which are present in both prokaryotes and eukaryotes, play a major role in cell protein quality control and survival of bacteria in harsh environmental conditions. Recently, a member of this protein family, ClpK was identified in a pathogenic strain of Klebsiella pneumoniae which was responsible for nosocomial infections. ClpK is linked to the thermal stress survival of this pathogen. The genome wide analysis of Clp proteins in Klebsiella spp. indicates that ClpK is present in only 34% of the investigated strains. This suggests that the uptake of the clpk gene is selective and may only be taken up by a pathogen that needs to survive harsh environmental conditions. In silico analyses and molecular dynamic simulations show that ClpK is mainly α-helical and is highly dynamic. ClpK was successfully expressed and purified to homogeneity using affinity and anion exchange chromatography. Biophysical characterization of ClpK showed that it is predominantly alpha-helical, and this is in agreement with in silico analysis of the protein structure. Furthermore, the purified protein is biologically active and hydrolyses ATP in a concentration- dependent manner.

Glutathione transferases (GSTs) are the main detoxification enzymes in schistosomes. These parasitic enzymes tend to be upregulated during drug treatment, with Schistosoma haematobium being one of the species that mainly affect humans. There is a lack of complete sequence information on the closely related bovis and haematobium 26-kDa GST isoforms in any database. Consequently, we engineered a pseudo-26-kDa S. bovis/haematobium GST (Sbh26GST) to understand structure–function relations and ligandin activity towards selected potential ligands. Sbh26GST was overexpressed in Escherichia coli as an MBP-fusion protein, purified to homogeneity and catalyzed 1-chloro-2,4-dinitrobenzene-glutathione (CDNB-GSH) conjugation activity, with a specific activity of 13 μmol/min/mg. This activity decreased by ~95% in the presence of bromosulfophthalein (BSP), which showed an IC₅₀ of 27 µM. Additionally, enzyme kinetics revealed that BSP acts as a non-competitive inhibitor relative to GSH. Spectroscopic studies affirmed that Sbh26GST adopts the canonical GST structure, which is predominantly α-helical. Further extrinsic 8-anilino-1-naphthalenesulfonate (ANS) spectroscopy illustrated that BSP, praziquantel (PZQ), and artemisinin (ART) might preferentially bind at the dimer interface or in proximity to the hydrophobic substrate-binding site of the enzyme. The Sbh26GST-BSP interaction is both enthalpically and entropically driven, with a stoichiometry of one BSP molecule per Sbh26GST dimer. Enzyme stability appeared enhanced in the presence of BSP and GSH. Induced fit ligand docking affirmed the spectroscopic, thermodynamic, and molecular modelling results. In conclusion, BSP is a potent inhibitor of Sbh26GST and could potentially be rationalized as a treatment for schistosomiasis.