Phenolics Profiling of Carpobrotus edulis (L.) N.E.Br. and Insights into Molecular Dynamics of Their Significance in Type 2 Diabetes Therapy and Its Retinopathy Complication

Abstract

Adverse effects associated with synthetic drugs in diabetes therapy has prompted the search for novel natural lead compounds with little or no side effects. Effects of phenolic compounds from Carpobrotus edulis on carbohydrate-metabolizing enzymes through in vitro and in silico methods were assessed. Based on the half-maximal inhibitory concentrations (IC50), the phenolic extract of the plant had significant (p < 0.05) in vitro inhibitory effect on the specific activity of alpha-amylase (0.51 mg/mL), alpha-glucosidase (0.062 mg/mL) and aldose reductase (0.75 mg/mL), compared with the reference standards (0.55, 0.72 and 7.05 mg/mL, respectively). Molecular interactions established between the 11 phenolic compounds identifiable from the HPLC chromatogram of the extract and active site residues of the enzymes revealed higher binding affinity and more structural compactness with procyanidin (−69.834 ± 6.574 kcal/mol) and 1,3-dicaffeoxyl quinic acid (−42.630 ± 4.076 kcal/mol) as potential inhibitors of alpha-amylase and alpha-glucosidase, respectively, while isorhamnetin-3-O-rutinoside (−45.398 ± 4.568 kcal/mol) and luteolin-7-O-beta-d-glucoside (−45.102 ± 4.024 kcal/mol) for aldose reductase relative to respective reference standards. Put together, the findings are suggestive of the compounds as potential constituents of C. edulis phenolic extract responsible for the significant hypoglycemic effect in vitro; hence, they could be exploited in the development of novel therapeutic agents for type-2 diabetes and its retinopathy complication.

Molecular modelling identification of phytocompounds from selected African botanicals as promising therapeutics against druggable human host cell targets of SARS-CoV-2

“…The interactions observed with both ABA and KOR towards hACE2 could be a probable justification for their higher binding affinities relative to MLN. Hydrogen bonds as well as van der Waals and other non-covalent interactions such as alkyl interactions are known to significantly add to the binding energy values of ligands after binding to a receptor [ 49 , 50 ] and based on this observation, ABA and KOR could be identified to have had good interactions with the protein in a manner that enhanced affinity suggestive of their potential inhibitory effect on hACE2.

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“…The RMSF is an assessment of how the amino acid residues of a receptor move or fluctuates as a result of a binding of a drug [ 50 , 59 , 60 ]. Increased RMSF value is an indication of increase in flexible movements of the alpha-carbon atoms [ 8 ].…”

Astaxanthin‐Mediated Bacterial Lethality: Evidence from Oxidative Stress Contribution and Molecular Dynamics Simulation

“…In sharp contrast to this observation, the lower RMSD value for novobiocin implied that it had a better capacity to improve structural stability of GyrB than astaxanthin. The RoG evaluates the compactness and stability of the resulting complex during MDS, and a more stable complex is usually indicated by a lower RoG value [ 20 ]. In this study, the observed relatively similar average RoG values of astaxanthin with unbound protein and reference antibiotics in complexation with GyrA, GyrB, PaC, and ParE further support the RMSD results.…”

“…The post-dynamic data was examined as previously described [ 20 ], and analysis of radius of gyration (ROG) and root mean square deviation (RMSD) were done followed by evaluation of the free binding energy and comparing the binding affinity of the resulting complex in each scenario of the simulation. The MDS was averaged among 100000 snapshots taken from a 60 ns MDS, and using the expression Δ G bind = G complex –( G Receptor + G ligand ), the free binding energy (Δ G ) was estimated.…”

Molecular Docking and Molecular Dynamics Studies of Antidiabetic Phenolic Compound Isolated from Leaf Extract of Englerophytum magalismontanum (Sond.) T.D.Penn.

“…Although several therapeutic options are available for the management of diabetes mellitus, treatment is associated with adverse side effects, complications, and the inability to prevent the deterioration of pancreatic β-cells [ 6 , 8 , 9 ]. As a result, there is a need for effective treatments, and the use of plant-based products is proposed as an alternative treatment method [ 10 ].…”