Evaluation of the Antihyperglycaemic Activities, Safety and Phytochemical Profile of Celtis zenkeri Engl

Objective: The study evaluated the hyperglycaemia-lowering effects, safety, and phytochemical profile of Celtis zenkeri leaf extract in order to justify its antidiabetic folkloric usage. Methods:  Modified OECD test guidelines were used to assess its acute and sub-acute toxicity while its effect on blood parameters such as blood glucose, and haematological and biochemical levels were evaluated using appropriate assays. Both in vitro and in vivo antihyperglycaemic assays were used for the antidiabetic studies while histology of the pancreas, liver, and kidney of the rats was examined after treatment with the extract at 250, 500, and 1000 mg/kg for 21 days.  GC-MS analysis was used to determine the chemical constituents of the extract. Results: The results obtained showed that the leaf extract of C. zenkeri was not toxic in rats at 5000 mg/kg. It elicited a significant decrease in the blood glucose levels of the animals but did not affect the haematological and biochemical components of normal rats. It significantly inhibited α-amylase and α-glucosidase actions and gave comparable activity to glibenclamide (5 mg/kg) at all time points at 200 and 400 mg/kg. The extract comparably reduced blood glucose levels with glibenclamide at 100 and 200 mg/kg on days 10 and 14 in drug-induced diabetic rats and maintained the histoarchitecture of the liver, kidney, and pancreas at 250 and 500 mg/kg.Conclusion: The study justified the ethnomedicinal use of C. zenkeri in diabetes management

Computational Assessment of Xanthones from African Medicinal Plants as Aldose Reductase Inhibitors

Diabetes mellitus is a life-threatening non-communicable disease that affects all age groups. Despite the increased attention it has received in recent years, the number of diabetic patients has grown exponentially. These increased cases are attributed to essential enzymes involved in blood glucose regulation. In this study, we attempt to reveal the aldose reductase inhibitory potential of xanthones isolated from African medicinal plants. Ensemble docking, molecular dynamics simulation, density functional theory (DFT), and ADMET methods were employed to identify drug candidates as aldose reductase inhibitors. The ensemble docking results identified mangostenone B, bangangxanthone A, smeathxanthone B, mangostenone A, and allanxanthone B as potent inhibitors against the aldose reductase enzyme. Molecular dynamics studies showed the xanthones established better binding mode and affinities against the enzyme. Moreover, the electronic properties of the xanthones explained their good pharmacological potentials. Therefore, our findings suggest that the hit molecules be investigated in vitro and in vivo for drug development against aldose reductase

Elucidating the Glucokinase Activating Potentials of Naturally Occurring Prenylated Flavonoids: An Explicit Computational Approach

Glucokinase activators are considered as new therapeutic arsenals that bind to the allosteric activator sites of glucokinase enzymes, thereby maximizing its catalytic rate and increasing its affinity to glucose. This study was designed to identify potent glucokinase activators from prenylated flavonoids isolated from medicinal plants using molecular docking, molecular dynamics simulation, density functional theory, and ADMET analysis. Virtual screening was carried out on glucokinase enzymes using 221 naturally occurring prenylated flavonoids, followed by molecular dynamics simulation (100 ns), density functional theory (B3LYP model), and ADMET (admeSar 2 online server) studies. The result obtained from the virtual screening with the glucokinase revealed arcommunol B (−10.1 kcal/mol), kuwanon S (−9.6 kcal/mol), manuifolin H (−9.5 kcal/mol), and kuwanon F (−9.4 kcal/mol) as the top-ranked molecules. Additionally, the molecular dynamics simulation and MM/GBSA calculations showed that the hit molecules were stable at the active site of the glucokinase enzyme. Furthermore, the DFT and ADMET studies revealed the hit molecules as potential glucokinase activators and drug-like candidates. Our findings suggested further evaluation of the top-ranked prenylated flavonoids for their in vitro and in vivo glucokinase activating potentials