Computational study of the inhibitory potential of Gongronema latifolium (benth) leave on farnesyl pyrophosphate synthase, a target enzyme in the treatment of osteoporosis. A molecular modelling approach

Background & Aim: Osteoporosis is an increasing medical threat which is referred to as a systemic skeletal disorder that is characterized mainly by low bone mass and microarchitectural wear of bone tissue and strength, which eventually results in an increase in the fragility of bone and makes bone to be susceptible to fracture. Osteoporosis is known globally as a severe health problem affecting approximately 200 million people worldwide. Therefore, a pharmacological solution is urgently needed. Studies have shown that farnesyl pyrophosphate synthase is a crucial enzyme in the mevalonate pathway that causes bone resorption, thus serving as a key pharmacological target. Experimental: Gongronema latifolium’s (Benth) phytoconstituents were screened against the mevalonate pathway enzyme farnesyl pyrophosphate synthase computationally using molecular docking, pharmacokinetics screening and Molecular Mechanics/Generalized Born Surface Area approach to identify compounds with the better inhibitorypotentials against this target in this study. Results: The study resulted that five compounds; hyperoside, rutin, epigallocatechin-3-gallate, kaempferol-3-arabinoside, and isoquercetin show a better inhibitory potential by binding to the active site of farnesyl pyrophosphate synthase compared with a co-crystalized ligand. These hit compounds were further subjected to pharmacokinetics studies to predict their drug-likeness and toxicity characteristics which show that all hit compounds except Rutin are drug-like leaving Kaempferol-3-Arabinoside as the most drug-like hit compound compared to the co-crystallized ligand. Recommended applications/industries: This study suggests that G. latifolium leaf could be a good plant source for a drug-like compound that may treat osteoporosis by inhibiting the farnesyl pyrophosphate synthase, in the mevalonate pathway, thereby stopping bone resorption

Comparison of nutritional composition, HPLC characterization, antioxidants property and starch profile of Sphenostylis stenocarpa composite bread and wheat bread

Background & Aim: The use of composite flour and combined additives in wheat flour to improve their nutritional and health benefits have increased. This study focuses on the examination and comparison of the phenolic characterization, antioxidant properties, mineral content, starch profile, in vitro starch digestibility and in vitro α-amylase inhibition present in produced composite bread and wheat bread. Experimental: Sphenostylis stenocarpa flour (SSF) and combined additives (dry gluten powder, fungal α-amylase and sodium stearoyl-2-lactylate) were incorporated into wheat flour to produce composite SSF bread. Wheat flour bread was prepared as a control. Results: The HPLC result showed higher values of gallic acid (1806.68 µg/100 g), p-coumaric acid (104.49 µg/100 g) and quercetin (22054.67 µg/100 g) in SSF bread while sinapic acid (195.88 µg/100 g), caffeic acid (1372.90 µg/100 g), ferulic acid (535.79 µg/100 g) were higher in control bread. Ferric-reducing antioxidant properties and mineral contents (Zinc, Ca, Fe, K, Mg, Mn and copper) were higher in SSF in comparison to control bread (P<0.05). The SSF bread had higher resistant starch and slowly digestible starch values but decreased total starch and rapidly digestible starch values. The in vitro starch digestibility (IVSD) value was also 0.54 times lower in SSF compared to control bread. The α-amylase inhibitory potential of SSF bread (56.77%) was significantly higher (P<0.05) in comparison to control bread (29.96%). It could be concluded that the incorporation of Sphenostylis stenocarpa in baked products such as bread will be of high nutritional benefits to humans. Recommended applications/industries: Sphenostylis stenocarpa is an underutilized bean that is rich in minerals, antioxidant properties and slow starch digestion potency which can be explored to prevent or manage the pathologic conditions that are related to sugar metabolisms. The utilization of underutilized Sphenostylis stenocarpa will go a long way in combating food insecurity

Potential Inhibitory Biomolecular Interactions of Natural Compounds With Different Molecular Targets of Diabetes

Type II diabetes is an endemic disease and is responsible for approximately 90% to 95% of diabetes cases. The pathophysiological distortions are majorly β-cell dysfunction, insulin resistance, and long-term inflammation, which all progressively unsettle the control of blood glucose levels and trigger microvascular and macrovascular complications. The diverse pathological disruptions which patients with type II diabetes mellitus exhibit precipitate the opinion that different antidiabetic agents, administered in combination, might be required to curb this menace and maintain normal blood glucose. To this end, natural compounds were screened to identify small molecular weight compounds with inhibitory effects on protein tyrosine phosphatase 1B (PTP1B), dipeptidyl-peptidase-4 (DPP-4), and α-amylase. From the result, the top 5 anthocyanins with the highest binding affinity are reported herein. Further ADMET profiling showed moderate pharmacokinetic profiles for these compounds as well as insignificant toxicity. Cyanidin 3-(p-coumaroyl)-diglucoside-5-glucoside (−15.272 kcal/mol), cyanidin 3-O-(6ʺ-malonyl-3ʺ-glucosyl-glucoside) (−9.691 kcal/mol), and delphinidin 3,5-O-diglucoside (−12.36 kcal/mol) had the highest binding affinities to PTP1B, DPP-4, and α-amylase, respectively, and can be used in combination to control glucose fluctuations. However, validations must be carried out through further in vitro and in vivo tests